Spectrum of dermatophyte infections in Botswana

PubMed Central

Thakur, Rameshwari

2015-01-01

Background Dermatophyte infections are a common cause of superficial fungal infection in different geographical locations of the world. Usually, it involves superficial invasion of keratinized tissue, eg, skin, nails, and hair, but in immunosuppressed individuals, it may cause atypical, extensive and deep lesions, which may pose serious diagnostic and therapeutic challenges. Aim To find out the causative dermatophyte species responsible for the various clinical types of dermatophyte infection. Results Trichophyton violaceum was found to be the predominant species, being the causative organism responsible for all the clinical types. Conclusion T. violaceum was found to be the most common species responsible for most of the clinical forms of dermatophytosis (96; 80%). Tinea unguium was found to be the most frequent clinical type of dermatophytosis (33; 27.50%). PMID:25834462

Spectrum of dermatophyte infections in Botswana.

PubMed

Thakur, Rameshwari

2015-01-01

Dermatophyte infections are a common cause of superficial fungal infection in different geographical locations of the world. Usually, it involves superficial invasion of keratinized tissue, eg, skin, nails, and hair, but in immunosuppressed individuals, it may cause atypical, extensive and deep lesions, which may pose serious diagnostic and therapeutic challenges. To find out the causative dermatophyte species responsible for the various clinical types of dermatophyte infection. Trichophyton violaceum was found to be the predominant species, being the causative organism responsible for all the clinical types. T. violaceum was found to be the most common species responsible for most of the clinical forms of dermatophytosis (96; 80%). Tinea unguium was found to be the most frequent clinical type of dermatophytosis (33; 27.50%).

Black Dot Tinea Capitis in an Immunosuppressed Man

PubMed Central

Mendese, Gary W.; Loo, Daniel S.

2013-01-01

Tinea capitis is a common superficial fungal infection of the scalp primarily afflicting young children. In adults, this infection may have an atypical presentation that may lead to a delay in diagnosis. The authors present a case report of black dot tinea capitis in an immunosuppressed Asian man with psoriasis and provide a review of the literature. PMID:23710273

Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans.

PubMed

Luo, Shanshan; Skerka, Christine; Kurzai, Oliver; Zipfel, Peter F

2013-12-15

Candida albicans is a medically important fungus that can cause a wide range of diseases ranging from superficial infections to disseminated disease, which manifests primarily in immuno-compromised individuals. Despite the currently applied anti-fungal therapies, both mortality and morbidity caused by this human pathogenic fungus are still unacceptably high. Therefore new prophylactic and therapeutic strategies are urgently needed to prevent fungal infection. In order to define new targets for combating fungal disease, there is a need to understand the immune evasion strategies of C. albicans in detail. In this review, we summarize different sophisticated immune evasion strategies that are utilized by C. albicans. The description of the molecular mechanisms used for immune evasion does on one hand help to understand the infection process, and on the other hand provides valuable information to define new strategies and diagnostic approaches to fight and interfere with Candida infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of pathogenic fungi with an optoelectronic nose

PubMed Central

Zhang, Yinan; Askim, Jon R.; Zhong, Wenxuan; Orlean, Peter; Suslick, Kenneth S.

2014-01-01

Human fungal infections have gained recent notoriety following contamination of pharmaceuticals in the compounding process. Such invasive infections are a more serious global problem, especially for immunocompromised patients. While superficial fungal infections are common and generally curable, invasive fungal infections are often life-threatening and much harder to diagnose and treat. Despite the increasing awareness of the situation’s severity, currently available fungal diagnostic methods cannot always meet diagnostic needs, especially for invasive fungal infections. Volatile organic compounds produced by fungi provide an alternative diagnostic approach for identification of fungal strains. We report here an optoelectronic nose based on a disposable colorimetric sensor array capable of rapid differentiation and identification of pathogenic fungi based on their metabolic profiles of emitted volatiles. The sensor arrays were tested with 12 human pathogenic fungal strains grown on standard agar medium. Array responses were monitored with an ordinary flatbed scanner. All fungal strains gave unique composite responses within 3 hours and were correctly clustered using hierarchical cluster analysis. A standard jackknifed linear discriminant analysis gave a classification accuracy of 94% for 155 trials. Tensor discriminant analysis, which takes better advantage of the high dimensionality of the sensor array data, gave a classification accuracy of 98.1%. The sensor array is also able to observe metabolic changes in growth patterns upon the addition of fungicides, and this provides a facile screening tool for determining fungicide efficacy for various fungal strains in real time. PMID:24570999

Skin microbiome changes in patients with interdigital tinea pedis.

PubMed

Wang, R; Song, Y; Du, M; Yang, E; Yu, J; Wan, Z; Li, R

2018-04-28

Tinea pedis is a chronic, recurrent superficial fungal infection that most commonly involves the toe web spaces. 1 Previous culture-based studies have incompletely defined the microbial landscape associated with tinea pedis, which was considered the result of infection with a single fungus. However, the recalcitrant course of the disease suggests that microbial community shifts have a role in disease pathogenesis. 2 This study was conducted to characterize the bacterial and fungal microbiome changes associated with interdigital tinea pedis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tinea versicolor, tinea nigra, white piedra, and black piedra.

PubMed

Bonifaz, Alexandro; Gómez-Daza, Fernando; Paredes, Vanessa; Ponce, Rosa María

2010-03-04

Superficial mycoses are fungal infections limited to the stratum corneum and its adnexal structures. The most frequent types are dermatophytoses or tineas. Tinea versicolor involves the skin in the form of hypochromic or hyperchromic plaques, and tinea nigra affects the skin of the palms with dark plaques. White piedra and black piedra are parasitic infections of scalp hairs in the form of concretions caused by fungal growth. Diagnosis of these mycoses is made from mycologic studies, direct examination, stains, and isolation, and identification of the fungi. Treatment includes systemic antifungals, topical antifungals, and keratolytics. Copyright 2010 Elsevier Inc. All rights reserved.

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis.

PubMed

Veasey, John Verrinder; Avila, Ricardo Bertozzi de; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries.

White piedra in a mother and daughter.

PubMed

Roshan, Anupama S; Janaki, C; Parveen, B

2009-07-01

White Piedra is a superficial fungal infection of the hair caused by Trichosporon asahii. It is also known as trichomycosis nodosa or trichomycosis nodularis. We report two cases of White Piedra in a mother and her daughter for the rarity of such occurrence.

Common Child and Adolescent Cutaneous Infestations and Fungal Infections.

PubMed

Alter, Sherman J; McDonald, Megan B; Schloemer, Julie; Simon, Ryan; Trevino, Julian

2018-01-01

Cutaneous infections and infestations are common among children and adolescents. Ectoparasitic infestations affect individuals across the globe. Head lice, body lice, scabies, and infestations with bed bugs are seen in individuals who reside in both resource poor areas and in developed countries. Superficial cutaneous and mucosal candida infections occur throughout the life cycle. Dermatophyte infections of keratin-containing skin and skin structures result in tinea capitis (scalp), tinea corporis (body), tinea pedis (foot), and tinea unguium (nails). Less frequent endemic fungal infections such as blastomycosis, coccidiodomycosis, and histoplasmosis may present with skin findings. This article will describe the epidemiology and transmission of these conditions as well as their clinical manifestations. The approach to diagnosis will be addressed as well as primary prevention and current therapies. Copyright © 2018 Mosby, Inc. All rights reserved.

DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

PubMed

Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

2015-01-01

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis*

PubMed Central

Veasey, John Verrinder; de Avila, Ricardo Bertozzi; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries. PMID:29186263

The microbiome-metabolome crosstalk in the pathogenesis of respiratory fungal diseases.

PubMed

Gonçalves, Samuel M; Lagrou, Katrien; Duarte-Oliveira, Cláudio; Maertens, Johan A; Cunha, Cristina; Carvalho, Agostinho

2017-08-18

Filamentous fungi of the genus Aspergillus are responsible for several superficial and invasive infections and allergic syndromes. The risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and pathogen exposure. There is increasing evidence that the individual microbiome supervises the outcome of the host-fungus interaction by influencing mechanisms of immune regulation, inflammation, metabolism, and other physiological processes. Microbiome-mediated mechanisms of resistance allow therefore the control of fungal colonization, preventing the onset of overt disease, particularly in patients with underlying immune dysfunction. Here, we review this emerging area of research and discuss the contribution of the microbiota (and its dysbiosis), including its immunoregulatory properties and relationship with the metabolic activity of commensals, to respiratory fungal diseases. Finally, we highlight possible strategies aimed at decoding the microbiome-metabolome dialog and at its exploitation toward personalized medical interventions in patients at high risk of infection.

[The burden of fungal infections in Algeria].

PubMed

Chekiri-Talbi, M; Denning, D W

2017-06-01

In Algeria, superficial mycoses are very commonly diagnosed. Deep fungal infections are less often observed. Few data from Algeria are found in the literature. We report for the first time the main causes of these diseases in our country and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the Service (Office) of the Statistics (ONES), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants and probably at least 568,900 (1.41 %) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems as there are over 1 million adult asthmatics. Candidaemia is estimated in 2020, invasive aspergillosis in 2865, intra-abdominal candidiasis in 303 people and are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer among including 1500 in children) and nor is COPD (an estimated 317,762 patients of whom 20.3 % are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Looking into Candida albicans infection, host response, and antifungal strategies.

PubMed

Wang, Yan

2015-01-01

Candida albicans, a commonly encountered fungal pathogen, causes diseases varying from superficial mucosal complaints to life-threatening systemic disorders. Among the virulence traits of C. albicans, yeast-to-hypha transition is most widely acknowledged. Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs), and defence against C. albicans infection is provided by an exquisite interplay between the innate and adaptive arms of the host immune system.

The fungus Trichophyton redellii sp. nov. causes skin infections that resemble white-nose syndrome of hibernating bats

USGS Publications Warehouse

Lorch, Jeffrey M.; Minnis, Andrew M.; Meteyer, Carol U.; Redell, Jennifer A.; White, J. Paul; Kaarakka, Heather M.; Muller, Laura K.; Lindner, David L.; Verant, Michelle L.; Shearn-Bochsler, Valerie I.; Blehert, David S.

2014-01-01

Before the discovery of white-nose syndrome (WNS), a fungal disease caused by Pseudogymnoascus destructans, there were no reports of fungal skin infections in bats during hibernation. In 2011, bats with grossly visible fungal skin infections similar in appearance to WNS were reported from multiple sites in Wisconsin, USA, a state outside the known range of P. destructans and WNS at that time. Tape impressions or swab samples were collected from affected areas of skin from bats with these fungal infections in 2012 and analyzed by microscopy, culture, or direct DNA amplification and sequencing of the fungal internal transcribed spacer region (ITS). A psychrophilic species ofTrichophyton was isolated in culture, detected by direct DNA amplification and sequencing, and observed on tape impressions. Deoxyribonucleic acid indicative of the same fungus was also detected on three of five bat carcasses collected in 2011 and 2012 from Wisconsin, Indiana, and Texas, USA. Superficial fungal skin infections caused by Trichophyton sp. were observed in histopathology for all three bats. Sequencing of the ITS of Trichophyton sp., along with its inability to grow at 25 C, indicated that it represented a previously unknown species, described herein as Trichophyton redellii sp. nov. Genetic diversity present within T. redellii suggests it is native to North America but that it had been overlooked before enhanced efforts to study fungi associated with bats in response to the emergence of WNS.

The fungus Trichophyton redellii sp. Nov. Causes skin infections that resemble white-nose syndrome of hibernating bats.

PubMed

Lorch, Jeffrey M; Minnis, Andrew M; Meteyer, Carol U; Redell, Jennifer A; White, J Paul; Kaarakka, Heather M; Muller, Laura K; Lindner, Daniel L; Verant, Michelle L; Shearn-Bochsler, Valerie; Blehert, David S

2015-01-01

Before the discovery of white-nose syndrome (WNS), a fungal disease caused by Pseudogymnoascus destructans, there were no reports of fungal skin infections in bats during hibernation. In 2011, bats with grossly visible fungal skin infections similar in appearance to WNS were reported from multiple sites in Wisconsin, US, a state outside the known range of P. destructans and WNS at that time. Tape impressions or swab samples were collected from affected areas of skin from bats with these fungal infections in 2012 and analyzed by microscopy, culture, or direct DNA amplification and sequencing of the fungal internal transcribed spacer region (ITS). A psychrophilic species of Trichophyton was isolated in culture, detected by direct DNA amplification and sequencing, and observed on tape impressions. Deoxyribonucleic acid indicative of the same fungus was also detected on three of five bat carcasses collected in 2011 and 2012 from Wisconsin, Indiana, and Texas, US. Superficial fungal skin infections caused by Trichophyton sp. were observed in histopathology for all three bats. Sequencing of the ITS of Trichophyton sp., along with its inability to grow at 25 C, indicated that it represented a previously unknown species, described herein as Trichophyton redellii sp. nov. Genetic diversity present within T. redellii suggests it is native to North America but that it had been overlooked before enhanced efforts to study fungi associated with bats in response to the emergence of WNS.

Nodules on the hair: a rare case of mixed piedra.

PubMed

Khatu, Swapna S; Poojary, Shital Amin; Nagpur, Niranjan G

2013-10-01

Piedra is a superficial fungal infection of the hair shaft characterized by nodules along the hair shaft. Black piedra affects the scalp hair more frequently than white piedra. Occurrence of both types of piedra simultaneously in a patient is extremely rare. We describe here a rare case of mixed piedra of scalp hair.

Fungal infections of the mucous membrane.

PubMed

Marques, Silvio Alencar

2010-01-01

A clinical review of three potentially severe fungal diseases, which are characterized in many cases by mucosal involvement, is presented. They are paracoccidioidomycosis, histoplasmosis, and mucormycosis. Mucosal involvement for paracoccidioidomycosis and rhinocerebral mucormycosis is frequent. Thus, oral involvement may provide early clue for diagnosis. In paracoccidioidomycosis, the mucosal lesion classically shows superficial ulcers with granular appearance and hemorrhagic points, usually on lips, palate, and jugal mucosa. In mucormycosis, necrosis of the palate followed for purulent discharge is a hallmark of rhinocerebral disease. Treatment with amphotericin B desoxycholate or the new second-generation triazoles is highly efficacious.

Gene flow contributes to diversification of the major fungal pathogen Candida albicans.

PubMed

Ropars, Jeanne; Maufrais, Corinne; Diogo, Dorothée; Marcet-Houben, Marina; Perin, Aurélie; Sertour, Natacha; Mosca, Kevin; Permal, Emmanuelle; Laval, Guillaume; Bouchier, Christiane; Ma, Laurence; Schwartz, Katja; Voelz, Kerstin; May, Robin C; Poulain, Julie; Battail, Christophe; Wincker, Patrick; Borman, Andrew M; Chowdhary, Anuradha; Fan, Shangrong; Kim, Soo Hyun; Le Pape, Patrice; Romeo, Orazio; Shin, Jong Hee; Gabaldon, Toni; Sherlock, Gavin; Bougnoux, Marie-Elisabeth; d'Enfert, Christophe

2018-06-08

Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify.

Clinical and Laboratory Characteristics of a Tinea Capitis Outbreak Among Novice Buddhist Monks.

PubMed

Bunyaratavej, Sumanas; Leeyaphan, Charussri; Rujitharanawong, Chuda; Muanprasat, Chanai; Matthapan, Lalita

2017-05-01

Sixty novice Buddhist monks with tinea capitis confirmed according to clinical presentation and mycological laboratory finding were included in this study. Mixed-type clinical presentation was observed in approximately half of all cases, together with scarring alopecia (95%) and superficial fungal skin infection at locations other than the scalp (43.3%). The major isolated organism was Trichophyton violaceum, and mixed-organism infection was found in 27 cases (45%). Slow-onset presentation and an extensive area of infection were significantly associated with mixed-type clinical presentation. © 2017 Wiley Periodicals, Inc.

Epidemiologic surveillance of cutaneous fungal infection in the United States from 1999 to 2002.

PubMed

Foster, K Wade; Ghannoum, Mahmoud A; Elewski, Boni E

2004-05-01

Cutaneous fungal infections are common in the United States, and causative organisms include dermatophytes, yeasts, and nondermatophyte molds. These organisms are in constant competition for their particular environmental niche, often resulting in the emergence of one or more predominant pathogens and displacement of other less competitive species. Changes in the incidence of fungal pathogens can be followed from laboratory culture results of infected cutaneous tissues over time. These data can be used to ascertain past and present trends in incidence, predict increases in antifungal resistance and the adequacy of our current pharmacologic repertoire, and provide insight into future developments. This study identifies epidemiologic trends and the predominant organisms causing superficial fungal infections in the United States. A total of 15,381 specimens were collected from clinically suspected tinea corporis, tinea cruris, tinea capitis, tinea faciei, tinea pedis, tinea manuum, and finger and toe onychomycosis from 1999 through 2002. Specimens were submitted to the Center for Medical Mycology in Cleveland, Ohio, for fungal culture and identification, and the incidence of each species was calculated. Dermatophytes remain the most commonly isolated fungal organisms except from clinically suspected finger onychomycosis, in which case Candida species comprise >70% of isolates. Trichophyton rubrum remains the most prevalent fungal pathogen, and increased incidence of this species was observed in finger and toe onychomycosis, tinea corporis and tinea cruris, tinea manuum, and tinea pedis. As the causal agent of tinea capitis, T tonsurans continues to increase in incidence, achieving near exclusionary proportions in the United States. Consideration of the current epidemiologic trends in the incidence of cutaneous fungal pathogens is of key importance to investigational efforts, diagnosis, and treatment.

Multiple rare opportunistic and pathogenic fungi in persistent foot skin infection.

PubMed

Chan, Giek Far; Sinniah, Sivaranjini; Idris, Tengku Idzzan Nadzirah Tengku; Puad, Mohamad Safwan Ahmad; Abd Rahman, Ahmad Zuhairi

2013-03-01

Persistent superficial skin infection caused by multiple fungi is rarely reported. Recently, a number of fungi, both opportunistic and persistent in nature were isolated from the foot skin of a 24-year old male in Malaysia. The fungi were identified as Candida parapsilosis, Rhodotorula mucilaginosa, Phoma spp., Debaryomyces hansenii, Acremonium spp., Aureobasidium pullulans and Aspergillus spp., This is the first report on these opportunistic strains were co-isolated from a healthy individual who suffered from persistent foot skin infection which was diagnosed as athlete's foot for more than 12 years. Among the isolated fungi, C. parapsilosis has been an increasingly common cause of skin infections. R. mucilaginosa and D. hansenii were rarely reported in cases of skin infection. A. pullulans, an emerging fungal pathogen was also being isolated in this case. Interestingly, it was noted that C. parapsilosis, R. mucilaginosa, D. hansenii and A. pullulans are among the common halophiles and this suggests the association of halotolerant fungi in causing persistent superficial skin infection. This discovery will shed light on future research to explore on effective treatment for inhibition of pathogenic halophiles as well as to understand the interaction of multiple fungi in the progress of skin infection.

Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India

PubMed Central

Srinivasan, M; Gonzales, C.; George, C.; Cevallos, V.; Mascarenhas, J.; Asokan, B; Wilkins, J.; Smolin, G.; Whitcher, J.

1997-01-01

AIMS/BACKGROUND—To determine the epidemiological characteristics and risk factors predisposing to corneal ulceration in Madurai, south India, and to identify the specific pathogenic organisms responsible for infection.
METHODS—All patients with suspected infectious central corneal ulceration presenting to the ocular microbiology and cornea service at Aravind Eye Hospital, Madurai, from 1 January to 31 March 1994 were evaluated. Sociodemographic data and information pertaining to risk factors were recorded, all patients were examined, and corneal cultures and scrapings were performed.
RESULTS—In the 3 month period 434 patients with central corneal ulceration were evaluated. A history of previous corneal injury was present in 284 patients (65.4%). Cornea cultures were positive in 297 patients (68.4%). Of those individuals with positive cultures 140 (47.1%) had pure bacterial infections, 139 (46.8%) had pure fungal infections, 15 (5.1%) had mixed bacteria and fungi, and three (1.0%) grew pure cultures of Acanthamoeba. The most common bacterial pathogen isolated was Streptococcus pneumoniae, representing 44.3% of all positive bacterial cultures, followed by Pseudomonas spp (14.4%). The most common fungal pathogen isolated was Fusarium spp, representing 47.1% of all positive fungal cultures, followed by Aspergillus spp (16.1%).
CONCLUSIONS—Central corneal ulceration is a common problem in south India and most often occurs after a superficial corneal injury with organic material. Bacterial and fungal infections occur in equal numbers with Streptococcus pneumoniae accounting for the majority of bacterial ulcers and Fusarium spp responsible for most of the fungal infections. These findings have important public health implications for the treatment and prevention of corneal ulceration in the developing world.

 PMID:9505820

Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions

PubMed Central

MacCallum, Donna M.; Brown, Gordon D.

2017-01-01

ABSTRACT   The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. PMID:28119468

Common drug-drug interactions in antifungal treatments for superficial fungal infections.

PubMed

Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H

2018-04-01

Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance. Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed. Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.

Clinicoepidemiological and Mycological Study of Tinea Capitis in the Pediatric Population of Kashmir Valley: A Study from a Tertiary Care Centre

PubMed Central

Bhat, Yasmeen J.; Zeerak, Sumaya; Kanth, Farhat; Yaseen, Atiya; Hassan, Iffat; Hakak, Rubina

2017-01-01

Background: Tinea capitis is a superficial fungal infection that predominantly affects the pediatric population. The etiological factors vary from region to region, and the exact incidence remains obscure. The clinicoepidemiological and mycological aspects of this dermatophytosis were studied in a tertiary care centre in Kashmir valley. Aim: To determine the clinicoepidemiological aspects and mycological findings of dermatophytes involved in tinea capitis cases in Kashmir valley. Materials and Methods: Wood's lamp examination, KOH examination, and fungal culture were performed in one hundred fifty clinically diagnosed cases of tinea capitis with patients’ age upto 14 years over a period of 6 months. The epidemiological factors associated with the disease were also evaluated. Results: Tinea capitis was predominant in the 3–6 and 6–9 years age groups with a male preponderance. Grey patch tinea capitis was the most common variant. KOH positivity was 76%, and Trichophyton tonsurans was the most common fungal isolate. Conclusion: Tinea capitis is a very common fungal infection in our setting. Early detection and diagnosis is mandatory to prevent its spread in the community as well as the development of scarring alopecia in the affected individual. PMID:28405548

Clinicoepidemiological and Mycological Study of Tinea Capitis in the Pediatric Population of Kashmir Valley: A Study from a Tertiary Care Centre.

PubMed

Bhat, Yasmeen J; Zeerak, Sumaya; Kanth, Farhat; Yaseen, Atiya; Hassan, Iffat; Hakak, Rubina

2017-01-01

Tinea capitis is a superficial fungal infection that predominantly affects the pediatric population. The etiological factors vary from region to region, and the exact incidence remains obscure. The clinicoepidemiological and mycological aspects of this dermatophytosis were studied in a tertiary care centre in Kashmir valley. To determine the clinicoepidemiological aspects and mycological findings of dermatophytes involved in tinea capitis cases in Kashmir valley. Wood's lamp examination, KOH examination, and fungal culture were performed in one hundred fifty clinically diagnosed cases of tinea capitis with patients' age upto 14 years over a period of 6 months. The epidemiological factors associated with the disease were also evaluated. Tinea capitis was predominant in the 3-6 and 6-9 years age groups with a male preponderance. Grey patch tinea capitis was the most common variant. KOH positivity was 76%, and Trichophyton tonsurans was the most common fungal isolate. Tinea capitis is a very common fungal infection in our setting. Early detection and diagnosis is mandatory to prevent its spread in the community as well as the development of scarring alopecia in the affected individual.

[Topical terbinafine. Reduction of duration of therapy for tinea pedis].

PubMed

Schmid-Wendtner, M-H; Korting, H

2008-12-01

Superficial fungal infections are common and worldwide in distribution. Latest estimates suggest one- third of the population in Europe has a fungal infection of their feet, with dermatophyte infections of the skin of the feet (tinea pedis) most common. Tinea pedis interdigitalis is by far most common and can be effectively treated topically. Common agents include azoles, hydroxypyridones and allylamines, with morpholines used less frequently. While most antifungals have mainly fungistatic effects on dermatophytes, the causative agents of tinea pedis, terbinafine--an allylamine--is fungicidal. Due to this feature shorter treatment periods are possible using topical terbinafine. For effective treatment of uncomplicated tinea pedis interdigitalis, azole cream preparations are often used twice daily for four weeks whereas 1% terbinafine cream can be applied once a day for one week. Since 2006, 1% terbinafine is also available as a film-forming solution (FFS), which makes single-dose treatment possible. FFS may prove superior in daily practice with increased compliance and thus reduced recurrences.

Sustained Protection against Superficial Bacterial and Fungal Infection by Topical Treatment.

DTIC Science & Technology

1974-12-31

from 1:100 to 1:1,000,000. The test organisms were a cutaneous micrococcus (Baird-Parker type 3), a diphtheroid, C. minutis- simum, Pseudomonas...all aluminum salts. Aluminum chlorhydroxide killed the micrococcus and diphtheroid out to the 1:1000 dilution. Aluminum chloride was lethal to the... micrococcus and diphtheroid only at the 1:100 concentration. Aluminum acetate was lethal only to the micrococcU . at the 1:100 concentration. COMMENT All

Cutaneous protothecosis.

PubMed

Hillesheim, Paul B; Bahrami, Soon

2011-07-01

Prototheca species are an achlorophyllic algae that cause infections primarily in immunocompromised individuals. At least one-half of infectious cases are cutaneous. Because protothecosis is seldom suspected clinically, patients may be subjected to various treatment modalities for extended periods without satisfactory results. Cutaneous protothecosis shares similar clinical and pathologic findings with deep tissue fungal mycoses. The typical presentation occurs most commonly on the face and extremities as erythematous plaques, nodules, or superficial ulcers. Prototheca spp are spherical, unicellular, nonbudding organisms that are sometimes noted on routine hematoxylin-eosin staining but are best visualized with periodic acid-Schiff and Gomori methenamine-silver histochemical stains. Although protothecosis can be diagnosed on biopsy, culture of the organism on a medium such as Sabouraud dextrose agar is required for definitive diagnosis. Treatment may require a combination of surgical excision and antifungal agents. Therefore, cutaneous protothecosis should be considered in a lesion that appears suspicious for the more-common fungal infections.

Noninvasive spectroscopic diagnosis of superficial ocular lesions and corneal infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourant, J.R.; Bigio, I.J.; Johnson, T.

The potential of a rapid noninvasive diagnostic system to detect tissue abnormalities on the surface of the eye has been investigated. The optical scatter signal from lesions and normal areas on the conjunctival sclera of the human eye were measured in vivo. It is possible to distinguish nonpigmented pingueculas from other lesions. The ability of the system to detect malignancies could not be tested because none of the measured and biopsied lesions were malignant. Optical scatter and fluorescence spectra of bacterial and fungal suspensions, and corneal irritations were also collected. Both scattering and fluorescence show potential for diagnosing corneal infections.

Species distribution and antifungal susceptibility of Candida spp. isolated from superficial candidiasis in outpatients in Iran.

PubMed

Razzaghi-Abyaneh, M; Sadeghi, G; Zeinali, E; Alirezaee, M; Shams-Ghahfarokhi, M; Amani, A; Mirahmadi, R; Tolouei, R

2014-06-01

Candidiasis is the most prevalent fungal infection affecting human and animals all over the world. This study represents the epidemiological aspects of superficial candidiasis in outpatients and in vitro antifungal susceptibility of etiologic Candida species. Clinical samples were taken from 173 patients including skin and nail scrapings (107; 61.8%), vaginal discharge (28; 16.2%), sputum (20; 11.6%), oral swabs (7; 4.0%), bronchoalveolar lavage (6; 3.5%) and 1 specimen (0.6%) of each eye tumor, gastric juice, urine, biopsy and urinary catheter and confirmed as candidiasis by direct microscopy, culture and histopathology. Susceptibility patterns of the isolated Candida species were determined using the disk diffusion and broth microdilution methods. Among 173 Candida isolates, C. albicans (72.3%) was the most prevalent species followed by C. parapsilosis (11.5%). Other identified species were C. glabrata, C. krusei, C. tropicalis, C. guilliermondii, C. intermedia and C. sake. Majority of the Candida isolates were susceptible to fluconazole (95.4%) followed by 5-flucytosine (89.6%), voriconazole (78.6%) itraconazole (48.0%) and ketoconazole (42.8%). Caspofungin was the most potent antifungal drug against C. albicans (MICs; 0.062-1 μg/mL), ketoconazole for C. parapsilosis and C. tropicalis (MICs; 0.031-0.25 μg/mL) and itraconazole for C. krusei, C. glabrata and C. guilliermondii (MICs; 0.031-1 μg/mL). This study reinforces the significance of superficial candidiasis as an important fungal infection with multiple clinical presentations. Our results further indicate that susceptibility testing to commonly used antifungals is crucial in order to select the appropriate therapeutic strategies which minimize complications while improving patients' life. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

D-optimal experimental approach for designing topical microemulsion of itraconazole: Characterization and evaluation of antifungal efficacy against a standardized Tinea pedis infection model in Wistar rats.

PubMed

Kumar, Neeraj; Shishu

2015-01-25

The study aims to statistically develop a microemulsion system of an antifungal agent, itraconazole for overcoming the shortcomings and adverse effects of currently used therapies. Following preformulation studies like solubility determination, component selection and pseudoternary phase diagram construction, a 3-factor D-optimal mixture design was used for optimizing a microemulsion having desirable formulation characteristics. The factors studied for sixteen experimental trials were percent contents (w/w) of water, oil and surfactant, whereas the responses investigated were globule size, transmittance, drug skin retention and drug skin permeation in 6h. Optimized microemulsion (OPT-ME) was incorporated in Carbopol based hydrogel to improve topical applicability. Physical characterization of the formulations was performed using particle size analysis, transmission electron microscopy, texture analysis and rheology behavior. Ex vivo studies carried out in Wistar rat skin depicted that the optimized formulation enhanced drug skin retention and permeation in 6h in comparison to conventional cream and Capmul 908P oil solution of itraconazole. The in vivo evaluation of optimized formulation was performed using a standardized Tinea pedis model in Wistar rats and the results of the pharmacodynamic study, obtained in terms of physical manifestations, fungal-burden score, histopathological profiles and oxidative stress. Rapid remission of Tinea pedis from rats treated with OPT-ME formulation was observed in comparison to commercially available therapies (ketoconazole cream and oral itraconazole solution), thereby indicating the superiority of microemulsion hydrogel formulation over conventional approaches for treating superficial fungal infections. The formulation was stable for a period of twelve months under refrigeration and ambient temperature conditions. All results, therefore, suggest that the OPT-ME can prove to be a promising and rapid alternative to conventional antifungal therapies against superficial fungal infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion.

PubMed

Mailänder-Sánchez, Daniela; Braunsdorf, Christina; Grumaz, Christian; Müller, Christoph; Lorenz, Stefan; Stevens, Philip; Wagener, Jeanette; Hebecker, Betty; Hube, Bernhard; Bracher, Franz; Sohn, Kai; Schaller, Martin

2017-01-01

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

Dermatology for the practicing allergist: Tinea pedis and its complications

PubMed Central

Al Hasan, Muhannad; Fitzgerald, S Matthew; Saoudian, Mahnaz; Krishnaswamy, Guha

2004-01-01

Tinea pedis is a chronic fungal infection of the feet, very often observed in patients who are immuno-suppressed or have diabetes mellitus. The practicing allergist may be called upon to treat this disease for various reasons. Sometimes tinea infection may be mistaken for atopic dermatitis or allergic eczema. In other patients, tinea pedis may complicate allergy and asthma and may contribute to refractory atopic disease. Patients with recurrent cellulitis may be referred to the allergist/immunologist for an immune evaluation and discovered to have tinea pedis as a predisposing factor. From a molecular standpoint, superficial fungal infections may induce a type2 T helper cell response (Th2) that can aggravate atopy. Th2 cytokines may induce eosinophil recruitment and immunoglobulin E (IgE) class switching by B cells, thereby leading to exacerbation of atopic conditions. Three groups of fungal pathogens, referred to as dermatophytes, have been shown to cause tinea pedis: Trychophyton sp, Epidermophyton sp, and Microsporum sp. The disease manifests as a pruritic, erythematous, scaly eruption on the foot and depending on its location, three variants have been described: interdigital type, moccasin type, and vesiculobullous type. Tinea pedis may be associated with recurrent cellulitis, as the fungal pathogens provide a portal for bacterial invasion of subcutaneous tissues. In some cases of refractory asthma, treatment of the associated tinea pedis infection may induce remission in airway disease. Very often, protracted topical and/or oral antifungal agents are required to treat this often frustrating and morbid disease. An evaluation for underlying immuno-suppression or diabetes may be indicated in patients with refractory disease. PMID:15050029

Common features of periocular tinea.

PubMed

Basak, S Alison Finger; Berk, David R; Lueder, Gregg T; Bayliss, Susan J

2011-03-01

To present the common features of periocular tinea to aid physicians in future diagnosis and therapy of this condition, because superficial fungal infections on the face are often misdiagnosed owing to the diverse morphologies that they manifest. This is especially true of dermatophytoses involving the periocular region. A retrospective review was performed of patients with a diagnosis of periocular tinea who were seen between January 2003 and September 2009 in the pediatric dermatology clinic at St. Louis Children's Hospital. Ten cases of periocular tinea were identified (6 male patients and 4 female patients). Common features included prolonged misdiagnosis (all 10 cases), a normal ophthalmologic examination (all 10 cases), and inappropriate corticosteroid application (7 cases). Loss of the eyelashes occurred in all 10 patients. No cases had evidence of other tinea infections on examination. Only 2 cases had the central clearing classically associated with tinea corporis. Seven patients had a potassium hydroxide preparation and/or culture positive for fungal elements. Lesions improved with topical and oral antifungal treatment in all cases, and patients were able to regrow their eyelashes. Periocular tinea should be considered in the differential diagnosis for periocular inflammation, especially in those patients refractory to therapy for more common conditions. Loss of the eyelashes is characteristic of these fungal infections, similar to the hair loss that occurs in kerions associated with tinea capitis.

Clinical appearances, healing patterns, risk factors, and outcomes of horses with fungal keratitis: 53 cases (1978-1996)

PubMed

Gaarder, J E; Rebhun, W C; Ball, M A; Patten, V; Shin, S; Erb, H

1998-07-01

To compare initial clinical appearances, healing mechanisms, risk factors, and outcomes of horses with fungal keratitis. Retrospective analysis. 52 horses (53 eyes) with fungal keratitis. Medical records and clinical photographs of eyes were reviewed. Keratomycoses were categorized on the basis of clinical appearance at initial examination and pattern of healing. Five distinct forms of mycotic keratitis were recognized. Of 53 affected eyes, 34 (64%) retained sight and had varying degrees of corneal scarring after treatment, 6 (11%) had a cosmetic appearance but were blind, and 13 (25%) were enucleated. Bacterial-like ulcers were the most frequent type and the most difficult for predicting outcome. Eyes affected by superficial fungal keratitis were likely to be chronically infected and to require debridement and extended treatment but usually healed with minimal scarring. Keratomycosis with a surrounding furrow resulted in a grave prognosis. Aspergillus organisms were isolated from 9 of 10 such eyes. Cake-frosting material was a positive prognostic sign. Fungal corneal stromal abscesses tended to be caused by yeast. This information will aid practitioners in recognizing various forms of fungal keratitis and guide them when making therapeutic decisions and prognoses for affected horses.

Self-resolving superficial primary cutaneous mucormycosis in a 7-week-old infant.

PubMed

Jones, Milissa U; Flores, Michelle S; Vereen, Rasheda J; Szabo, Sabrina R; Logemann, Nicholas F; Eberly, Matthew D

2018-05-30

A 7-week-old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self-resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Skin diseases during floods in Thailand.

PubMed

Vachiramon, Vasanop; Busaracome, Ploysyne; Chongtrakool, Piriyaporn; Puavilai, Siripen

2008-04-01

Floods are natural disasters that occur occasionally in Thailand. The most common form skin diseases due to floods are infectious dermatoses especially superficial fungal infection. However the microbiologic evidences have not been evaluated. To evaluate the most common skin diseases during floods and identify the organism that causes skin maceration at web space(s) of toes (Hong Kong foot). Patients who complained of skin problems were evaluated at the temporary outpatient clinic during October 2006. Skin specimens from all patients who had itches and skin maceration at web space(s) of toes were cultured. Ninety-six patients were evaluated (38 males and 58 females). Eczema was the most prevalent dermatosis, which accounted for 34.5% of the total skin problems and the great majority of these cases were irritant contact dermatitis. Sixteen cases presented with itch and skin maceration at web space(s) of toes. All of them were colonized with various microorganisms. Gram-negative bacilli were the most prevalent ones and were found in 14 out of 16 specimens. Fungal culture was positive in only two specimens. Eczema is the most common dermatosis during floods. Skin maceration at web space(s) of toes, which were thought to be fungal infection, are chronic irritant dermatitis with secondary bacterial colonization. Only a few cases were fungal infection. Microbiologic investigation should be done in these patients. Unfortunately, it is not practical in such a situation. Topical medications that have the combination of antiinflammatory, antibacterial and antifungal properties are the most suitable medications.

Aspergillus--classification and antifungal susceptibilities.

PubMed

Buzina, Walter

2013-01-01

Aspergillus is one of the most important fungal genera for the man, for its industrial use, its ability to spoil food and not least its medical impact as cause of a variety of diseases. Currently hundreds of species of Aspergillus are known; nearly fifty of them are able to cause infections in humans and animals. Recently, the genus Aspergillus is subdivided into 8 subgenera and 22 sections. The spectrum of diseases caused by Aspergillus species varies from superficial cutaneous to invasive and systemic infections. All species of Aspergillus investigated so far are resistant against the antifungals fluconazole and 5-fluorocytosine, the range of susceptibilities to currently available antifungals is discussed in this paper.

[Mycoses in Venezuela: Working Groups in Mycology reported cases (1984-2010)].

PubMed

Martínez Méndez, Dilia; Hernández Valles, Rosaura; Alvarado, Primavera; Mendoza, Mireya

2013-01-03

In 1984 the Venezuelan Work Groups in Mycology (VWGM) were created introducing an innovative approach to the study of the mycoses in Venezuela. To study the occurrence of the mycoses in Venezuela. Review the reported cases of mycoses by the newsletter Boletín Informativo Las Micosis en Venezuela (VWGM) from 1984 to 2010. The data collected showed 36,968 reported cases of superficial mycoses, 1,989 of deep systemic cases, and 822 of localized mycoses. Pityriasis dermatophytosis was the most common superficial infection, and paracoccidioidomycosis and histoplasmosis the most frequent deep systemic infection. Chromoblastomycosis was the most frequently diagnosed subcutaneous infection. The data provided showed the distribution by geographical area for each of the fungal infections studied, which may help to establish the endemic areas. Superficial mycosis is a public health problem due to its high morbidity and is probably responsible for some of the outbreaks in high-risk groups. Paracoccidioidomycosis and histoplasmosis were reported more often, which agrees with earlier reports prior to the formation of the VWGM. Cases of sporotrichosis and chromoblastomycosis in Venezuela can be considered unique due to the high number of cases. This study highlights the contribution of the VWGM to the behavior of the mycoses in Venezuela, its incidence, prevalence, and the recognition of these infections as a problem of public health importance. The VWGM should keep working in this endeavor, not only reporting new cases, but also unifying the clinical and epidemiological criteria, in order to properly monitor the evolving epidemiological changes reported in these types of infections. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier España, S.L. All rights reserved.

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

PubMed Central

Braunsdorf, Christina; Grumaz, Christian; Müller, Christoph; Lorenz, Stefan; Stevens, Philip; Wagener, Jeanette; Hebecker, Betty; Hube, Bernhard; Bracher, Franz; Sohn, Kai; Schaller, Martin

2017-01-01

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG. PMID:29023454

Fatal mycotic dermatitis in captive brown tree snakes (Boiga irregularis).

PubMed

Nichols, D K; Weyant, R S; Lamirande, E W; Sigler, L; Mason, R T

1999-03-01

Cutaneous fungal infections occurred in four captive brown tree snakes (Boiga irregularis). The ventral scales were most commonly affected, and lesions began as areas of erythema and edema with vesicle formation, followed by development of caseous brown plaques. Lesions usually started where ventral scales overlapped and spread rapidly. All snakes died within 14 days after clinical signs were first noted. The deaths of three of the snakes were directly attributable to the cutaneous disease; the other snake died from renal failure and visceral gout, most likely induced by gentamicin therapy. Histologically, lesions consisted of epidermal hyperplasia and hyperkeratosis, with foci of epidermal necrosis, intraepidermal vesicle formation, and subacute inflammation of the underlying dermis. These lesions were associated with bacteria and numerous septate, branched fungal hyphae within the epidermis and overlying serocelluar crusts. Hyphae that penetrated through the superficial surface of the epidermis often formed terminal arthroconidia. The same species of fungus was isolated in pure culture from the skin of three snakes, but fungal cultures were not performed on samples from the fourth snake. The fungus has been identified as the Chrysosporium anamorph of Nannizziopsis vriesii based on its formation of solitary dermatophytelike aleurioconidia and alternate and fission arthroconidia. The source of the fungus in this outbreak was not determined; however, the warm, moist conditions under which the snakes were housed likely predisposed them to opportunistic cutaneous fungal infections.

Dermatomycosis in lower limbs of diabetic patients followed by podiatry consultation.

PubMed

Parada, Helena; Veríssimo, Cristina; Brandão, João; Nunes, Baltazar; Boavida, José; Duarte, Rui; Peerally, Zulmira; Oliveira, Rui; Rosado, Laura; Sabino, Raquel

2013-01-01

Diabetic patients are particularly susceptible to fungal infections due to modifications that occur in their immunological system. These modifications compromise natural defences, such as skin and nails, especially from lower limbs. Assessing the presence of dermatomycosis in lower limbs of Portuguese diabetic patients followed on Podiatry consultation. Determination of possible predisposing factors and the most frequent fungal species associated with the cases are included in the study. A six-month prospective study was carried out in 163 diabetic patients with signs and symptoms of dermatomycosis followed by Podiatry at the Portuguese Diabetes Association in Lisbon. Samples from the skin and/or nails of the lower limbs were collected and demographic and clinical data of those patients were recorded. Trichophyton rubrum was the most frequently isolated dermatophyte (12.1%), followed by Trichophyton mentagrophytes (7.7%) and Trichophyton tonsurans (4.4%). Our study showed positive associations between type 2 diabetes and the presence of dermatomycosis in the studied population (p=0.013); this association was also shown between the occurrence of dermatomycosis and the localization of the body lesion (p=0.000). No other predisposing factor tested was positively associated with infection (p>0.05). Data on superficial fungal infections in diabetic patients are scarce in Portugal. This study provides information on the characterization of dermatomycosis in lower limbs of diabetic patients. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

[Animals as a potential source of human fungal infections].

PubMed

Dworecka-Kaszak, Bozena

2008-01-01

Changing environment is a reason, that many saprotrophic fungi became opportunists and in the end also maybe a pathogenic. Host specific adaptation is not so strong among fungi, so there are many common fungal pathogens for people and for animals. Animals suffering from dermatomycosis are well recognize as source of human superficial mycoses. Breeding of different exotic animals such as parrots, various Reptiles and Amphibians, miniature Rodents and keeping them as a pets in the peoples houses, have become more and more popular in the recent years. This article is shortly presenting which animals maybe a potential source of fungal infections for humans. Looking for the other mycoses as systemic mycoses, especially candidiasis or aspergilosis there are no data, which allow excluding sick animals as a source of infection for human, even if those deep mycoses have endogenic reactivation mechanism. Immunocompromised people are in high-risk group when they take care of animals. Another important source of potentially pathogenic, mostly air-born fungi may be animal use in experimental laboratory work. During the experiments is possible that laboratory workers maybe hurt and these animals and their environment, food and house boxes could be the possible source of microorganisms, pathogenic for humans or other animals. Unusual way to inoculate these potentially pathogens into the skin of laboratory personnel may cause granulomatous, local lesions on their hands.

Terbinafine-loaded wound dressing for chronic superficial fungal infections.

PubMed

Paskiabi, Farnoush Asghari; Bonakdar, Shahin; Shokrgozar, Mohammad Ali; Imani, Mohammad; Jahanshiri, Zahra; Shams-Ghahfarokhi, Masoomeh; Razzaghi-Abyaneh, Mehdi

2017-04-01

In spite of developing new drugs and modern formulations, the treatments of chronic fungal infections are still challenging. Fibrous wound dressings are new suggestions for the treatment of chronic superficial infections. In the present study, we formulated an antifungal agent, terbinafine hydrochloride (TFH), which is a hydrophobic drug, in wound dressings prepared by electrospun polycaprolactone, polycaprolactone/gelatin (50:50 w/w) and gelatin. To obtain more water-stable meshes, the preparations were treated by glutaraldehyde and their properties were determined before and after treatment. The morphology of fibrous meshes was observed by scanning electron microscopy. Drug loading efficiency and release rate were measured by high performance liquid chromatography (HPLC) and the release rate was monitored for 144h. Antifungal tests were performed on Trichophyton mentagrophytes, Aspergillus fumigatus and Candida albicans cultured on Muller-Hinton agar. The toxicity of the meshes was measured after 24h and 14days by MTT assay. Terbinafine loading of polycaprolactone/gelatin (50:50) was 100% and it released the highest amount of TFH too. In antifungal tests, all samples were able to hinderT. mentagrophytes and A. fumigatus but not C. albicans growth among them, polycaprolactone fibers made the largest inhibition zone. In MTT assay, none of prepared samples showed toxicity against L929 cells. Teken together, the prepared TFH-loaded PCL/gelatin electrospun meshes were able to release TFH slowly and in a steady state in time. With respect to no obvious cytotoxicity in MTT assay and stong antifungal activity toward T. mentagrophytesin vitro, these TFH-based meshes could be considered as potential candidates in clinical application as wound dressing for treatment of chronic dermatophytosis. Copyright © 2016 Elsevier B.V. All rights reserved.

[Mondor's disease of penis: A case report].

PubMed

Marsaudon, E; Legal, C; Gayoux, D; Weber, O

2016-09-01

Mondor's disease is a rare superficial thrombophlebitis, historically involving the thoracic venous system of women. However, it can occur in both gender and all over the skin. We report a 40-year-old man with type one diabetes who presented with a thrombosis of the superficial dorsal vein of the penis that he treated as a fungal infection. Treatment with non-steroidal anti-inflammatory drugs and low molecular weight heparin contributed to a favorable outcome in 2 weeks. Pathogenesis and treatment of Mondor's disease remain incompletely dominated. Some predisposing factors have been highlighted in the literature. It might be interesting to add diabetes, due to its frequent pelvic problems leading to a potential venous inflammatory trigger. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Animal Model of Dermatophytosis

PubMed Central

Shimamura, Tsuyoshi; Kubota, Nobuo; Shibuya, Kazutoshi

2012-01-01

Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host's normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects. PMID:22619489

Two cases of scalp white piedra caused by Trichosporon ovoides.

PubMed

Tambe, Swagata A; Dhurat, S Rachita; Kumar, Chaya A; Thakare, Preeti; Lade, Nitin; Jerajani, Hemangi; Mathur, Meenakshi

2009-01-01

White piedra is a superficial fungal infection of the hair shaft, caused by Trichosporon beigelii . We report two cases of white piedra presenting as brown palpable nodules along the hair shaft with a fragility of scalp hairs. T. beigelii was demonstrated in hair culture of both the patients and T. ovoides as a species was confirmed on carbohydrate assimilation test. The first patient responded to oral itraconazole and topical ketoconazole, with a decrease in the palpability of nodules and fragility of scalp hairs at the end of two months.

Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions.

PubMed

Wagener, Jeanette; MacCallum, Donna M; Brown, Gordon D; Gow, Neil A R

2017-01-24

The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host's arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the "conditionally essential" amino acid l-arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Manipulation of these host defense mechanisms by the pathogen can be key to successful host invasion. We show here that the human opportunistic fungal pathogen Candida albicans influences l-arginine availability for nitric oxide production by induction of the substrate-competing host enzyme arginase-1. This led to a reduced production of nitric oxide and, moreover, reduced eradication of the fungus by human macrophages. We demonstrate that blocking of host arginase-1 activity restored nitric oxide production and increased the killing potential of macrophages. These results highlight the therapeutic potential of l-arginine metabolism in fungal diseases. Copyright © 2017 Wagener et al.

Deep dermatophytosis and inherited CARD9 deficiency.

PubMed

Lanternier, Fanny; Pathan, Saad; Vincent, Quentin B; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; Del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad; Abel, Laurent; Lortholary, Olivier; Casanova, Jean-Laurent; Picard, Capucine; Grimbacher, Bodo; Puel, Anne

2013-10-31

Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.).

Deep Dermatophytosis and Inherited CARD9 Deficiency

PubMed Central

Vincent, Quentin B.; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad

2014-01-01

BACKGROUND Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. METHODS We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain–containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. RESULTS Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. CONCLUSIONS All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.) PMID:24131138

Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection.

PubMed

Saxena, Seema; Uniyal, Veena; Bhatt, R P

2012-10-01

Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides.

Lecythophora hoffmannii isolated from a case of canine osteomyelitis in Japan.

PubMed

Sakaeyama, Shin-Ichi; Sano, Ayako; Murata, Yoshiteru; Kamei, Katsuhiko; Nishimura, Kazuko; Hatai, Kishio

2007-05-01

A 2-year-old spayed female mongrel dog showed claudication with abnormal ossification containing fungal cells detected by biopsy. The dog was treated with ketoconazole and itraconazole perorally for 5 months; however, the osteomyelitis became aggravated, and an amputation from the scapula was performed. The right superficial cervical lymph node became swollen 5 months after the operation. The lymph node contained PAS positive fungal elements and a portion of tissue produced mycelial fungal growth on potato dextrose agar supplemented with chloramphenicol. The culture was identified as Lecythophora hoffmannii based on morphology, physiology and 100% identity in the sequence of the D1/D2 domain of the large subunit ribosomal RNA gene of the fungal species in the GenBank database (accession number AB100627). In addition, the sequence from the present isolate was submitted as AB189164. The isolate showed resistance to antifungal agents, i.e., amphotericin B, 5-FC, fluconazole, itraconazole, miconazole and micafungin. The dog developed cachexia 2 months after the onset of lymphadenopathy, and was euthanized on the 459th day after onset of clinical symptoms. This was the first disseminated case of L. hoffmannii infection in Japan.

Candida albicans Biofilms and Human Disease

PubMed Central

Nobile, Clarissa J.; Johnson, Alexander D.

2016-01-01

In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species. PMID:26488273

Diagnosis and Treatment of Paracoccidioidomycosis in the Maxillofacial Region: A Report of 5 Cases

PubMed Central

Araújo, André Vitor Alves; Cerqueira, Daniel Assunção; Cesconetto, Lorenzzo De Angeli; Provenzano, Nilton; de Oliveira, Eder Magno Ferreira

2018-01-01

Paracoccidioidomycosis is a fungal infection initially described in Brazil in 1908 by Adolfo Lutz. Manifestation of this disease depends on numerous factors, such as microorganism virulence, hormonal profile, genetic predisposition, nutrition, and immune system. It is characterized classically by cutaneous lesions, lymphadenopathy, and pulmonary involvement. It presents male predilection, which can be explained by the protective effect of female hormones. Classic presentation within oral cavity is a superficial ulcer characterized by hemorrhagic dots of moriform aspect. Treatment should be established individually and closely monitored. This manuscript aims at reporting five cases of this pathology. PMID:29850333

Diagnosis and Treatment of Paracoccidioidomycosis in the Maxillofacial Region: A Report of 5 Cases.

PubMed

Albuquerque Neto, Antonio Dionízio De; Araújo, André Vitor Alves; Cerqueira, Daniel Assunção; Cesconetto, Lorenzzo De Angeli; Provenzano, Nilton; de Oliveira, Eder Magno Ferreira

2018-01-01

Paracoccidioidomycosis is a fungal infection initially described in Brazil in 1908 by Adolfo Lutz. Manifestation of this disease depends on numerous factors, such as microorganism virulence, hormonal profile, genetic predisposition, nutrition, and immune system. It is characterized classically by cutaneous lesions, lymphadenopathy, and pulmonary involvement. It presents male predilection, which can be explained by the protective effect of female hormones. Classic presentation within oral cavity is a superficial ulcer characterized by hemorrhagic dots of moriform aspect. Treatment should be established individually and closely monitored. This manuscript aims at reporting five cases of this pathology.

Ciclopirox 1% shampoo for the treatment of seborrheic dermatitis.

PubMed

Gupta, Aditya K; Nicol, Karyn A

2006-01-01

Seborrheic dermatitis is a chronic superficial fungal infection of the skin, particularly affecting sites rich in sebaceous glands. Although the precise etiology of seborrheic dermatitis is uncertain, yeasts of the genus Malassezia are known to play a causative role. Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent, which also has anti-inflammatory properties. Ciclopirox is effective both in vitro and in vivo against Malassezia yeasts, making it a valuable option for the treatment of seborrheic dermatitis. Varying frequencies and concentrations of ciclopirox shampoo have been shown to be effective and safe in the treatment of seborrheic dermatitis of the scalp.

Antifungal Activity of Selenium Nanoparticles Synthesized by Bacillus species Msh-1 Against Aspergillus fumigatus and Candida albicans

PubMed Central

Shakibaie, Mojtaba; Salari Mohazab, Naser; Ayatollahi Mousavi, Seyyed Amin

2015-01-01

Background: Fungal infections affect various parts of the body and can be difficult to treat. Aspergillus infection causes a spectrum of diverse diseases particularly in lung according to host immunity. The two major entities are invasive pulmonary aspergillosis and chronic pulmonary aspergillosis. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes. However, invasive fungal infections are often life-threatening. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs. Objectives: In the present study, the antifungal activity of biogenic selenium nanoparticles (Se NPs) against Aspergillus fumigatus and Candida albicans was investigated. Materials and Methods: Se-reducing bacteria previously identified as Bacillus sp. MSh-1 were used for the intracellular biosynthesis of elemental Se NPs. The shape, size, and purity of the extracted NPs were determined with various instrumental techniques. The nanoparticles antifungal characterization mainly derives from the following pathways: (i) to generate sustained flux of nano-ions from the compounds that deposited on special substrates or imbedded in colloidal or semisolid matrices. (ii) To transport active those ions to sensitive targets on plasma membrane of fungi. Results: The results of energy-dispersive X-ray demonstrated that the purified NPs consisted of only Se. In addition, transmission electron micrographs showed that 120- to 140-nm spherical Se NPs were the most common. An antifungal assay was performed with a standard Clinical and Laboratory Standards Institute broth microdilution method. Minimum inhibitory concentration (MIC) measurements of the antifungal activity of the Se NPs against C. albicans (70 μg/mL) and A. fumigatus (100 μg/mL) showed that yeast cells were more sensitive than mold cells. Conclusions: The MICs against A. fumigatus (100 μg/mL) and C. albicans (70 μg/mL) showed that biogenic Se NPs are useful antifungal agents. PMID:26495111

Scanning electron microscopy of superficial white onychomycosis*

PubMed Central

de Almeida Jr., Hiram Larangeira; Boabaid, Roberta Oliveira; Timm, Vitor; Silva, Ricardo Marques e; de Castro, Luis Antonio Suita

2015-01-01

Superficial white onychomycosis is characterized by opaque, friable, whitish superficial spots on the nail plate. We examined an affected halux nail of a 20-year-old male patient with scanning electron microscopy. The mycological examination isolated Trichophyton mentagrophytes. Abundant hyphae with the formation of arthrospores were found on the nail's surface, forming small fungal colonies. These findings showed the great capacity for dissemination of this form of onychomycosis. PMID:26560225

A prodrug approach to the use of coumarins as potential therapeutics for superficial mycoses.

PubMed

Mercer, Derry K; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S; O Neil, Deborah A

2013-01-01

Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20-25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones.

A Prodrug Approach to the Use of Coumarins as Potential Therapeutics for Superficial Mycoses

PubMed Central

Mercer, Derry K.; Robertson, Jennifer; Wright, Kristine; Miller, Lorna; Smith, Shane; Stewart, Colin S.; O′Neil, Deborah A.

2013-01-01

Superficial mycoses are fungal infections of the outer layers of the skin, hair and nails that affect 20–25% of the world's population, with increasing incidence. Treatment of superficial mycoses, predominantly caused by dermatophytes, is by topical and/or oral regimens. New therapeutic options with improved efficacy and/or safety profiles are desirable. There is renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including the treatment of superficial mycoses. We investigated the potential of coumarins as dermatophyte-specific antifungal agents and describe for the first time their potential utility as topical antifungals for superficial mycoses using a prodrug approach. Here we demonstrate that an inactive coumarin glycone, esculin, is hydrolysed to the antifungal coumarin aglycone, esculetin by dermatophytes. Esculin is hydrolysed to esculetin β-glucosidases. We demonstrate that β-glucosidases are produced by dermatophytes as well as members of the dermal microbiota, and that this activity is sufficient to hydrolyse esculin to esculetin with concomitant antifungal activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited antifungal activity by preventing esculin hydrolysis. Esculin demonstrates good aqueous solubility (<6 g/l) and could be readily formulated and delivered topically as an inactive prodrug in a water-based gel or cream. This work demonstrates proof-of-principle for a therapeutic application of glycosylated coumarins as inactive prodrugs that could be converted to an active antifungal in situ. It is anticipated that this approach will be applicable to other coumarin glycones. PMID:24260474

Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection

PubMed Central

Saxena, Seema; Uniyal, Veena; Bhatt, R.P.

2012-01-01

Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides. PMID:24031963

Tinea Capitis in Children and Trichoscopic Criteria.

PubMed

Elghblawi, Ebtisam

2017-01-01

Tinea capitis is the most common pediatric superficial dermatophyte infection. The causative species vary, as for instance, Microsporum canis predominates in Europe, while Trichophyton tonsurans predominates in North America. Tinea capitis does not respond well to topical therapy alone, thus oral therapy is requisite. The drug of choice is griseofulvin; however in some countries, it is no longer available. Fungal culture should be requested in the persistent, scalp lesion and trichoscopy can put forward a speedy diagnosis by its characteristic findings. Scalp dermoscopy or "trichoscopy" represents a valuable, noninvasive technique for the evaluation of patients with hair loss due to tenia capitis. It is simple, quick, and easy to perform.

Synergy of the antibiotic colistin with echinocandin antifungals in Candida species.

PubMed

Zeidler, Ute; Bougnoux, Marie-Elisabeth; Lupan, Alexandru; Helynck, Olivier; Doyen, Antonia; Garcia, Zacarias; Sertour, Natacha; Clavaud, Cécile; Munier-Lehmann, Hélène; Saveanu, Cosmin; d'Enfert, Christophe

2013-06-01

Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden. A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains. We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination. These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins.

21 CFR 524.1005 - Furazolidone aerosol powder.

Code of Federal Regulations, 2011 CFR

2011-04-01

... infection of superficial wounds, abrasions, lacerations, and pyogenic dermatitis. (ii) Horses. For treatment or prevention of bacterial infection of superficial wounds, abrasions, lacerations, and following... bacterial infection of superficial wounds, abrasions, and lacerations caused by Staphylococcus aureus...

21 CFR 524.1005 - Furazolidone aerosol powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... infection of superficial wounds, abrasions, lacerations, and pyogenic dermatitis. (ii) Horses. For treatment or prevention of bacterial infection of superficial wounds, abrasions, lacerations, and following... bacterial infection of superficial wounds, abrasions, and lacerations caused by Staphylococcus aureus...

White-nose syndrome increases torpid metabolic rate and evaporative water loss in hibernating bats.

PubMed

McGuire, Liam P; Mayberry, Heather W; Willis, Craig K R

2017-12-01

Fungal diseases of wildlife typically manifest as superficial skin infections but can have devastating consequences for host physiology and survival. White-nose syndrome (WNS) is a fungal skin disease that has killed millions of hibernating bats in North America since 2007. Infection with the fungus Pseudogymnoascus destructans causes bats to rewarm too often during hibernation, but the cause of increased arousal rates remains unknown. On the basis of data from studies of captive and free-living bats, two mechanistic models have been proposed to explain disease processes in WNS. Key predictions of both models are that WNS-affected bats will show 1 ) higher metabolic rates during torpor (TMR) and 2 ) higher rates of evaporative water loss (EWL). We collected bats from a WNS-negative hibernaculum, inoculated one group with P. destructans , and sham-inoculated a second group as controls. After 4 mo of hibernation, TMR and EWL were measured using respirometry. Both predictions were supported, and our data suggest that infected bats were more affected by variation in ambient humidity than controls. Furthermore, disease severity, as indicated by the area of the wing with UV fluorescence, was positively correlated with EWL, but not TMR. Our results provide the first direct evidence that heightened energy expenditure during torpor and higher EWL independently contribute to WNS pathophysiology, with implications for the design of potential treatments for the disease. Copyright © 2017 the American Physiological Society.

Econazole imprinted textiles with antifungal activity.

PubMed

Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

2016-04-01

In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1 μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3 μg/cm(2)) was reproducible and stable up to 4 months storage at 25 °C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 °C, which enabled a larger drug release at 32 °C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Melanized Fungi in Human Disease

PubMed Central

Revankar, Sanjay G.; Sutton, Deanna A.

2010-01-01

Summary: Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections. PMID:20930077

Proteomics of eukaryotic microorganisms: The medically and biotechnologically important fungal genus Aspergillus.

PubMed

Kniemeyer, Olaf

2011-08-01

Fungal species of the genus Aspergillus play significant roles as model organisms in basic research, as "cell factories" for the production of organic acids, pharmaceuticals or industrially important enzymes and as pathogens causing superficial and invasive infections in animals and humans. The release of the genome sequences of several Aspergillus sp. has paved the way for global analyses of protein expression in Aspergilli including the characterisation of proteins, which have not designated any function. With the application of proteomic methods, particularly 2-D gel and LC-MS/MS-based methods, first insights into the composition of the proteome of Aspergilli under different growth and stress conditions could be gained. Putative targets of global regulators led to the improvement of industrially relevant Aspergillus strains and so far not described Aspergillus antigens have already been discovered. Here, I review the recent proteome data generated for the species Aspergillus nidulans, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Aspergillus flavus and Aspergillus oryzae. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antifungal prophylaxis during neutropenia and immunodeficiency.

PubMed Central

Lortholary, O; Dupont, B

1997-01-01

Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

Cutaneous Mycoses: Management and Education in Universities and Their Clinics in Japan.

PubMed

Mochizuki, Takashi

2016-01-01

In May 2015, information on the current status of mycological examinations in university clinics, and the education of students, and junior and senior residents in Japanese universities was gathered using a questionnaire, which was completed by 98 of the 117 (83.8%) professors or directors in charge of dermatology departments in Japan that were included in the survey.The questionnaire items were divided into three parts; namely, Part A, inspection methods used for diagnosis of cutaneous mycoses in each university clinic; Part B, need for a network and construction of a support system for medical care and education; and Part C, status of education of undergraduate students and residents. Some of these questions are based on a similar survey in 2007. In Part A, it was found that only 3% of university clinics performed fungal culture for all or most cases, indicating a drop from the previous study (9% in 2007). Meanwhile, responses indicating that fungal culture was almost or completely done away with accounted for about 36%. Based on type of mycoses, fungal culture for deep mycoses was performed in about 83% of the facilities. However, the percentage for superficial mycoses was very low, wherein only 39% of the facilities performed cultures even for tinea capitis. Trichophyton tonsurans infection was "often" or "sometimes" diagnosed in 22% of the facilities, with the other 78% reporting "no" or "almost no cases" of T. tonsurans infection diagnosed. In Part B, it was found that 96% of respondents (up from 89% in 2007) desired help from the university network, including aid in identifying fungal isolates, diagnosing rare fungal infections, and basic training in medical mycology of young doctors (senior residents in university hospitals). In Part C, it was found that education in direct KOH preparation for senior residents was satisfactory in about 80% of the facilities. However, about 45% of respondents reported that majority or all of the senior residents in their institutes had no opportunity to perform fungal culture. The results indicate that respondents desire a diagnostic laboratory for medical mycology, especially for rare (deep) mycoses, and a database for diagnosis and management of deep mycoses. It is still therefore necessary to continue an educational program targeted at leaders to educate those in charge of each department.

Bilateral Tinea Nigra Plantaris with Good Response to Isoconazole Cream: A Case Report.

PubMed

Falcão, Eduardo Mastrangelo Marinho; Trope, Beatriz Moritz; Martins, Natália Regina Pinto Guedes; Barreiros, Maria da Glória Carvalho; Ramos-E-Silva, Marcia

2015-01-01

Tinea nigra is a superficial fungal infection caused by Hortaea werneckii. It typically affects young individuals as an asymptomatic unilateral macule, from light brown to black on the palms and soles, mainly in tropical and subtropical regions. In 1997, Gupta et al. [Br J Dermatol 1997;137:483-484] described the dermoscopic characteristics of tinea nigra. Topical antifungals with or without keratolytic agents can be used for the treatment. The authors report a case of a 47-year-old man with asymptomatic light brown macules bilaterally on the plantar regions. Dermoscopic examination revealed brownish spicules consistent with the pattern described in the literature. Treatment with isoconazole cream was effective with complete resolution.

An Unusual Case of White Piedra Due to Trichosporon inkin Mimicking Trichobacteriosis.

PubMed

Zhuang, Kaiwen; Ran, Xin; Dai, Yaling; Tang, Jiaoqing; Yang, Qin; Pradhan, Sushmita; Ran, Yuping

2016-12-01

White piedra is a superficial mycosis characterized by soft, white-to-tan, irregular nodules attached to the hair shafts. A 36-year-old man presented with small lumps in his pubic hair, without any other symptoms. The clinical features were suggestive of trichobacteriosis. Pathology analysis of the infected hair revealed that the concretions surrounding the hair shaft were full of fungal elements, parts of which had invaded into the cuticle. Culture on Sabouraud dextrose agar grew creamy, yellow-white colonies identified as Trichosporon inkin by the sequence of the nuclear ribosomal intergenic spacer region. The condition was treated by shaving the pubic hair and administering antifungal therapy (oral itraconazole and topical ketoconazole).

Tinea Capitis in Children and Trichoscopic Criteria

PubMed Central

Elghblawi, Ebtisam

2017-01-01

Tinea capitis is the most common pediatric superficial dermatophyte infection. The causative species vary, as for instance, Microsporum canis predominates in Europe, while Trichophyton tonsurans predominates in North America. Tinea capitis does not respond well to topical therapy alone, thus oral therapy is requisite. The drug of choice is griseofulvin; however in some countries, it is no longer available. Fungal culture should be requested in the persistent, scalp lesion and trichoscopy can put forward a speedy diagnosis by its characteristic findings. Scalp dermoscopy or “trichoscopy” represents a valuable, noninvasive technique for the evaluation of patients with hair loss due to tenia capitis. It is simple, quick, and easy to perform. PMID:28839385

Cutaneous manifestations of non-Hodgkin's lymphoma.

PubMed

Kumar, S S; Kuruvilla, M; Pai, G S; Dinesh, M

2003-01-01

Thirty-two confirmed cases of non -Hodgkin's lymphoma (NHL) were examined for cutaneous manifestations for a period of 2 years from November 1998 in KMC Hospital Attavar, Mangalore. Cutaneous manifestations in the study group were compared to a control group of 32 patients. Specific infiltrates were present in all (5/5) CTCL patients and one out of twenty-seven patients with low grade NHL. Morphologically they presented as papules, plaques, nodules and erythroderma. Infective conditions seen in the study group were superficial fungal (7/32) and viral infections (2/ 32). Non-infective conditions were acquired ichthyosis (10/32), generalised pruritus (5/32), insect bite reaction (1/32) and drug eruption (1/32). When compared to control patients only acquired ichthyosis and generalised pruritus were found to be statistically significant. The study group also showed changes due to chemotherapy like diffuse alopecia (24/29), bluish pigmentation of proximal part of nail (4/29), localised pigmentation of palms and soles (1 /29), diffuse pigmentation at injection site (1 /29), pigmentation at scar site (1 /29) and stomatitis (4/29).

Skin Fungi from Colonization to Infection.

PubMed

de Hoog, Sybren; Monod, Michel; Dawson, Tom; Boekhout, Teun; Mayser, Peter; Gräser, Yvonne

2017-07-01

Humans are exceptional among vertebrates in that their living tissue is directly exposed to the outside world. In the absence of protective scales, feathers, or fur, the skin has to be highly effective in defending the organism against the gamut of opportunistic fungi surrounding us. Most (sub)cutaneous infections enter the body by implantation through the skin barrier. On intact skin, two types of fungal expansion are noted: (A) colonization by commensals, i.e., growth enabled by conditions prevailing on the skin surface without degradation of tissue, and (B) infection by superficial pathogens that assimilate epidermal keratin and interact with the cellular immune system. In a response-damage framework, all fungi are potentially able to cause disease, as a balance between their natural predilection and the immune status of the host. For this reason, we will not attribute a fixed ecological term to each species, but rather describe them as growing in a commensal state (A) or in a pathogenic state (B).

Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies.

PubMed

Kniemeyer, Olaf; Ebel, Frank; Krüger, Thomas; Bacher, Petra; Scheffold, Alexander; Luo, Ting; Strassburger, Maria; Brakhage, Axel A

2016-10-01

Filamentous fungi of the genus Aspergillus play significant roles as pathogens causing superficial and invasive infections as well as allergic reactions in humans. Particularly invasive mycoses caused by Aspergillus species are characterized by high mortality rates due to difficult diagnosis and insufficient antifungal therapy. The application of immunoproteomic approaches has a great potential to identify new targets for the diagnosis, therapy, and vaccine development of diseases caused by Aspergillus species. Serological proteome analyses (SERPA) that combine 2D electrophoresis with Western blotting are still one of the most popular techniques for the identification of antigenic proteins. However, recently a growing number of approaches have been developed to identify proteins, which either provoke an antibody response or which represent targets of T-cell immunity in patients with allergy or fungal infections. Here, we review advances in the studies of immune responses against pathogenic Aspergilli as well as the current status of diagnosis and immunotherapy of Aspergillus infections. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single oral paracoccidioidomycosis mimicking other lesions: report of eight cases.

PubMed

de Oliveira Gondak, Rogério; Mariano, Fernanda Viviane; dos Santos Silva, Alan Roger; Vargas, Pablo Agustin; Lopes, Márcio Ajudarte

2012-01-01

Paracoccidioidomycosis is a fungal infection caused by Paracoccidioides brasiliensis. It is an endemic disease, representing a serious health problem in Latin American countries. This infection primarily affects the lungs and is acquired by inhalation of the fungus. It can spread to other organs and tissues, mainly the oral cavity affecting more adult men from 30 to 50 years of age. On clinical presentation, several signs associated with impaired general and nutritional conditions can be noted. Oral manifestation is more common in the soft palate, gingiva, lower lip, buccal mucosa, and tongue. The classical clinical presentation is a superficial ulcer with granular appearance and hemorrhagic points. Usually, the oral lesion is extensive and generalized. Although uncommon, when the oral manifestation is single, others lesions, particularly squamous cell carcinoma, must be included in the differential diagnosis. In this article, the authors discuss the unusual presentation of eight cases of single oral paracoccidioidomycosis and its diagnostic importance.

Usefulness of Photodynamic Therapy in the Management of Onychomycosis.

PubMed

Robres, P; Aspiroz, C; Rezusta, A; Gilaberte, Y

2015-12-01

Onychomycosis, or fungal infection of the nails, is one of the most prevalent fungal diseases in the general population. Treatment is of limited effectiveness, tedious, and must be administered for long periods. Furthermore, systemic antifungal agents are associated with adverse effects. Photodynamic therapy (PDT) may prove to be a viable alternative in the treatment of superficial skin infections, including onychomycosis. We review articles relating to the usefulness of PDT in onychomycosis in both in vitro and in vivo settings and discuss the potential and limitations of various photosensitizing agents. In vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and 43% of cases, respectively, at 12 months. Finally, based on data in the literature and our own experience, we propose a protocol of 3 PDT sessions, separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a photosensitizing agent and red light (λ=630 nm, 37 J.cm(-2)). Each session is preceded by the topical application of urea 40% over several days. Clinical trials are needed to optimize PDT protocols and to identify those patients who will benefit most from this treatment. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Nannizziopsis guarroi infection in 2 Inland Bearded Dragons (Pogona vitticeps): clinical, cytologic, histologic, and ultrastructural aspects.

PubMed

Le Donne, Viviana; Crossland, Nicholas; Brandão, João; Sokolova, Yuliya; Fowlkes, Natalie; Nevarez, Javier G; Langohr, Ingeborg M; Gaunt, Stephen D

2016-06-01

Chrysosporium-related infections have been increasingly reported in reptiles over the last 2 decades. In this report, we describe clinical, cytologic, histopathologic, and ultrastructural aspects of Chrysosporium-related infection in 2 Inland Bearded Dragons (Pogona vitticeps). Case 1 was presented for an enlarging raised lesion over the left eye and multiple additional masses over the dorsum. Case 2 was submitted to necropsy by the referring veterinarian for suspected yellow fungus disease. Impression smears of the nodules in case 1 revealed granulomatous to pyogranulomatous inflammation and many septate, variably long, 4-10 μm wide, often undulated hyphae, and very rare conidia. Postmortem impression smears of the superficial lesions of case 2 contained large numbers of solitary conidia and arthroconidia and low numbers of hyphae with similar morphology to case 1. Histopathology of the 2 cases revealed severe, multifocal, chronic, ulcerative, nodular pyogranulomatous dermatitis, with myriad intralesional septate hyphae, and arthroconidia. Fungal culture and molecular sequencing in both cases indicated infection with Nannizziopsis guarroi. © 2016 American Society for Veterinary Clinical Pathology.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

PubMed Central

Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

2018-01-01

SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

Fungal Infections and New Biologic Therapies.

PubMed

Vallabhaneni, Snigdha; Chiller, Tom M

2016-05-01

The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality.

Comparison of modified Chicago sky blue stain and potassium hydroxide mount for the diagnosis of dermatomycoses and onychomycoses.

PubMed

Liu, Zhong; Sheng, Ping; Yang, Yan-Ping; Li, Wen; Huang, Wen-Ming; Wang, Jie-Di; Fan, Yi-Ming

2015-05-01

The diagnostic value of modified Chicago sky blue (CSB) stain and potassium hydroxide (KOH) mount for superficial mycoses was compared using fungal culture as gold standard. The sensitivity and screening time of the CSB stain were superior to the KOH mount. The CBS stain is simple, quick and reliable for diagnosing superficial mycoses. Copyright © 2015. Published by Elsevier B.V.

Infections Caused by Fusarium Species in Pediatric Cancer Patients and Review of Published Literature.

PubMed

Arnoni, Mariana Volpe; Paula, Claudete Rodrigues; Auler, Marcos Ereno; Simões, Cirilo Cesar Naozuka; Nakano, Shirley; Szeszs, Maria Walderez; Melhem, Márcia de Souza Carvalho; Pereira, Virgínia Bodelão Richini; Garces, Hans Garcia; Bagagli, Eduardo; Silva, Eriques Gonçalves; de Macêdo, Melissa Ferreira; Ruiz, Luciana da Silva

2018-03-21

Fusarium species have emerged as responsible for a broad spectrum of infections, including superficial, locally invasive and disseminated ones, especially in the hospital environment. Since there are few reports of invasive and disseminated fusariosis in children, the aim of this study was to report four cases of nosocomial infection caused by this microorganism in children with cancer hospitalized in a public children's hospital located in Brazil. Two of these patients were female and two were male. All patients presented febrile neutropenia, while three patients had acute lymphocytic leukemia and one patient had Wilms' tumor as underlying disease. In two cases, fungi were isolated from blood and identified as Fusarium oxysporum species complex after phenotypic and genotypic studies, while in two other cases fungi were isolated from skin biopsies and identified as Fusarium solani species complex. One patient died 12 days after the onset of cutaneous lesions. All isolates, after susceptibility testing, presented high levels of minimum inhibitory concentration for itraconazole, voriconazole and amphotericin B. Considering the emergence of filamentous fungi as etiologic agents of nosocomial infections, health professionals should be aware of the problems these infections, especially fungal ones, may cause to debilitated patients.

Molecular genetic techniques for gene manipulation in Candida albicans.

PubMed

Xu, Qiu-Rong; Yan, Lan; Lv, Quan-Zhen; Zhou, Mi; Sui, Xue; Cao, Yong-Bing; Jiang, Yuan-Ying

2014-05-15

Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains.

Antifungal activity of 10 Guadeloupean plants.

PubMed

Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

2013-11-01

Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. Copyright © 2012 John Wiley & Sons, Ltd.

Infection of the Beard area. Kerion: a review of 2 cases.

PubMed

Wall, D; Fraher, M; O'Connell, B; Watson, R; Timon, C; Stassen, L F A; Barnes, L

2014-01-01

Folliculitis barbae is a common condition of both infective and non-infectious aetiology. It most frequently presents as a superficial folliculitis, with fine pustules appearing at the opening of hair follicles in the beard area, often associated with shaving; known as Bockhart impetigo and usually due to infection caused by Staphylococcus aureus. If untreated, the infection and inflammation can progress, leading to a more deeply seated infection known as sycosis barbae. Perifollicular nodules, termed furuncles, may appear and when these are multiple and coalesce, a deep-seated, communicating, pustulating plaque called a carbuncle develops, often with associated systemic upset. Such an appearance, which can prompt incision and drainage, should not, however, be assumed to be solely due to staphylococcal infection. Particularly in the context of a history of close animal contact or a lack of response to antibiotic treatment, a diagnosis of tinea barbae should be considered and investigated. Prompt treatment with antifungal agents and often systemic steroids is required once the diagnosis is made. This will help reduce an exacerbation of the pronounced destruction that results from the immune response to the fungal infection, known as a kerion, which would be compounded by surgical intervention. In this article, we review two such cases and review the investigation and management of the disease.

Trichophyton rubrum osteomyelitis after calcaneus external fixation pin stabilization of a pilon fracture.

PubMed

Waryasz, Gregory R; Bariteau, Jason T

2014-01-01

Fungal organisms are an uncommon cause of osteomyelitis, and no dermatophyte osteomyelitis infections have been reported in published studies. We present the case of Trichophyton rubrum osteomyelitis of the calcaneus. Our patient initially presented with a pilon fracture requiring temporary external fixation while awaiting definitive fixation. From our review of the published data, the present case is the first of this type of fungal osteomyelitis to be reported. The patient was evaluated for a left neck mass during his hospitalization that was later found to be consistent with salivary duct carcinoma of the tail of the parotid gland. A left neck dissection and superficial excision of the parotid gland was performed after fixation of his pilon fracture. Subsequently, he developed an increasing lucency in the calcaneus and symptoms of pain and erythema months after the calcaneus pin had been removed. The osteomyelitis was treated with surgical debridement and 3 months of itraconazole once cultures had definitively grown T. rubrum. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Invasive Fungal Infections after Natural Disasters

PubMed Central

Benedict, Kaitlin

2014-01-01

The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed. PMID:24565446

Invasive fungal infections after natural disasters.

PubMed

Benedict, Kaitlin; Park, Benjamin J

2014-03-01

The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed.

Fungal Skin Infections

MedlinePlus

... Skin Infections Overview of Fungal Skin Infections Candidiasis (Yeast Infection) Dermatophytid Reaction Intertrigo Tinea Versicolor Overview of ... breasts. Common fungal skin infections are caused by yeasts (such as Candida or Malassezia furfur ) or dermatophytes , ...

Fungal Eye Infections

MedlinePlus

... fungal eye infections . Fungal eye infections are extremely rare, but they can be very serious. The most common way for someone to develop a fungal eye infection is as a result of an eye injury, particularly if the injury was caused by plant material such as a stick or a thorn. ...

Targeting Iron Acquisition Blocks Infection with the Fungal Pathogens Aspergillus fumigatus and Fusarium oxysporum

PubMed Central

Leal, Sixto M.; Roy, Sanhita; Vareechon, Chairut; Carrion, Steven deJesus; Clark, Heather; Lopez-Berges, Manuel S.; diPietro, Antonio; Schrettl, Marcus; Beckmann, Nicola; Redl, Bernhard; Haas, Hubertus; Pearlman, Eric

2013-01-01

Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by topical application of iron chelators or statins reduces fungal growth in the cornea by 60% and that dual therapy with the iron chelator deferiprone and statins further restricts fungal growth by 75%. Together, these studies identify specific host iron-chelating and fungal iron-acquisition mediators that regulate fungal growth, and demonstrate that therapeutic inhibition of fungal iron acquisition can be utilized to treat topical fungal infections. PMID:23853581

Targeting iron acquisition blocks infection with the fungal pathogens Aspergillus fumigatus and Fusarium oxysporum.

PubMed

Leal, Sixto M; Roy, Sanhita; Vareechon, Chairut; Carrion, Steven deJesus; Clark, Heather; Lopez-Berges, Manuel S; Di Pietro, Antonio; diPietro, Antonio; Schrettl, Marcus; Beckmann, Nicola; Redl, Bernhard; Haas, Hubertus; Pearlman, Eric

2013-01-01

Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by topical application of iron chelators or statins reduces fungal growth in the cornea by 60% and that dual therapy with the iron chelator deferiprone and statins further restricts fungal growth by 75%. Together, these studies identify specific host iron-chelating and fungal iron-acquisition mediators that regulate fungal growth, and demonstrate that therapeutic inhibition of fungal iron acquisition can be utilized to treat topical fungal infections.

The epidemiology of tinea manuum in Nanchang area, South China.

PubMed

Zhan, Ping; Geng, Chengfang; Li, Zhihua; Jiang, Qing; Jin, Yun; Li, Caixia; Liu, Weida

2013-08-01

Tinea manuum is a common superficial fungal infection which is usually coexistent with tinea pedis; there are few studies available on the epidemiology of tinea manuum at present. This study aims to investigate the epidemiology of tinea manuum and its correlation with tinea pedis in south China. A total of 280 patients with tinea manuum were recruited. The epidemiological and clinical data were analyzed, and causative agents were isolated and identified mycologically. Totally, 84.3 % patients with tinea manuum had co-occurrence of tinea pedis, among which 88.4 % patients had experience of scratching their feet. There was a significant relationship between the touch habits and the hand infection (χ(2) = 65.451, P = 0.000). More than 90 % patients had quite the same species of isolates from multiple infected sites in one patient. Therefore, it seems that transmission of dermatophytes from the feet to hand by scratching might be a most common way. As for tinea manuum, whether "unilateral" or "bilateral" is just the result that pathogens spread from feet to hand(s), which is only a special clinical presentation of tinea.

First case of mesh infection due to Coccidioides spp. and literature review of fungal mesh infections after hernia repair.

PubMed

Forrester, Joseph D; Gomez, Carlos A; Forrester, Jared A; Nguyen, Mike; Gregg, David; Deresinski, Stan; Banaei, Niaz; Weiser, Thomas G

2015-10-01

Fungal mesh infections are a rare complication of hernia repairs with mesh. The first case of Coccidioides spp. mesh infection is described, and a systematic literature review of all known fungal mesh infections was performed. Nine cases of fungal mesh infection are reviewed. Female and male patients are equally represented, median age is 49.5 years, and critical illness and preinfection antibiotic use were common. Fungal mesh infections are rare, but potentially fatal, complications of hernias repaired with mesh. © 2015 Blackwell Verlag GmbH.

Onychomycosis and tinea pedis in athletes from the State of Rio Grande Do Sul (Brazil): a cross-sectional study.

PubMed

Sabadin, Clarice Saggin; Benvegnú, Sérgio Augusto; da Fontoura, Mara Mary Carvalho; Saggin, Ligia Maria Fernandes; Tomimori, Jane; Fischman, Olga

2011-03-01

Onychomycosis and tinea pedis are common superficial infections caused primarily by dermatophytes. The aim of this investigation was to study the epidemiology, etiological agents, and potential risk factors for infection based on comparison of athletes and non-athletes from a northern region of Rio Grande do Sul (Brazil). Each group consisted of 100 male individuals with ages ranging from 18 to 40 years. After a clinical examination, samples were taken from individuals presenting signs of onychomycosis and/or tinea pedis for direct microscopic examination and culture. Among the athletes, the frequency of onychomycosis and/or tinea pedis was 32%, and for the control group, it was 20%. The athletes presented 16% of onychomycosis, 12% of tinea pedis, and 4% of onychomycosis and tinea pedis together. The distribution in the control group was 10% of onychomycosis, 7% of tinea pedis, and 3% of this association. The pathogens identified were dermatophytes (84.8%) and yeasts (15.2%), and the most commonly identified organism was Trichophyton rubrum, followed by Trichophyton mentagrophytes var. interdigitale. No significant differences were found when the frequency of species distribution in the athletes and non-athlete groups was compared. Risk factors for onychomycosis in athletes included familial cases of fungal infection, contact with domestic animals, and nail trauma, while the risk factors in non-athletes included the habit of not using sandals in public bathrooms and nail trauma. For tinea pedis, the habit of not using sandals in public bathrooms was a predisposing factor in both groups, while hyperhydrosis was a risk factor only in non-athletes. This study concludes that despite the higher number of fungal infections in athletes, there is no significant difference between these groups.

Production of an anti-dermatophyte monoclonal antibody and its application: immunochromatographic detection of dermatophytes

PubMed Central

Noriki, Sakon; Ishida, Hisaya

2016-01-01

Tinea refers to superficial infection with one of three fungal genera—Microsporum, Epidermophyton, or Trichophyton—that are collectively known as dermatophytes. These infections are among the most common diseases worldwide and cause chronic morbidity. They are usually diagnosed by direct microscopy and fungal culture, which are burdensome to perform in the clinical setting. To supplement conventional methods, we developed a new method that employs an immunochromatography test for detection of dermatophyte infections. First, anti-Trichophyton monoclonal antibodies (mAb) were produced in mice using a Trichophyton allergen solution as an immunogen. The mAb specificity was assessed by immunostaining alcohol fixed slide cultures and formalin fixed paraffin-embedded microbial samples. Both alcohol- and formalin-fixed samples of all seven species of Trichophyton tested displayed positive immunostaining. Immunochromatography test strips were created using the anti-Trichophyton mAb. The efficiency of the test strip was assessed in patients diagnosed with tinea unguium and in healthy volunteers. Of the 20 patient nails tested, 19 tested positive and one tested negative, whereas of the 17 volunteer nails, only one tested positive. However, KOH microscopic examination of the volunteer nail that tested positive revealed the existence of Trichophyton hyphae. Although the number of nails assayed was small, since the assay had a sensitivity of 95.0% (19/20) and a specificity of 94.1% (16/17), the obtained results were considered to be promising. Thus, while further investigation with a greater number of samples is necessary, this method could potentially be employed as a new diagnostic tool for Trichophyton in the future. PMID:27250927

Pityriasis Versicolor on Penile Shaft in a Renal Transplant Recipient

PubMed Central

Ryu, Han-Won; Cho, Jae-We

2012-01-01

Pityriasis versicolor is a superficial infection of the stratum corneum, which is caused by the Malassezia species. Tge Malassezia species consist of 12 subspecies, including M. furfur, M. pachydermatis, M. symphodialis and M. globasa. The Malassezia species are classified as a normal flora, particularly in the sebum rich areas of the skin, and they convert from saprophytic yeast to parasitic mycelial morpholgic form to cause clinical disease. But majorities of their distributions are in the upper back, the neck, the thighs, and the forearm, and not in the penis. It is well known that the renal transplant patients, who take immunosuppressive agents, have impairment in the protective cell mediated immunity. Thus, they are more susceptible to infectious diseases, such as a fungal infection. Therefore, clinical manifestations show higher incidence of disease, but they mostly occur in an expected distribution. We here report a case of pityriasis versicolor in a renal transplant recipient on penile shaft, which is an unusual area. PMID:22879720

Athlete's foot and fungally infected toenails

PubMed Central

Crawford, Fay; Hart, Rachel; Bell-Syer, Sally E M; Torgerson, David J; Young, Philip; Russell, Ian

2001-01-01

Definition Athlete's foot is a cutaneous fungal infection that causes the skin to itch, flake, and fissure. Nail involvement is characterised by ungual thickening and discoloration. Incidence/prevalence In the United Kingdom, athlete's foot is present in about 15% of the general population,1 and 1.2 million people have fungally infected toenails.2 Aetiology/risk factors Swimming pool users and industrial workers may have increased risk of fungal foot infection. However, one survey found fungal foot infection in only 8.5% of swimmers, with the highest incidence (20%) in men aged 16 years and over.1 Prognosis Fungal infections of the foot are not life threatening in people with normal immunity, but in some people they cause persistent symptoms. Other people seem to be oblivious of persistent infection. The infection can spread to other parts of the body and to other people. Aims To control symptoms and prevent recurrence, with minimal adverse effects. Outcomes Rates of fungal eradication, shown by negative microscopy and culture, and resolution of clinical signs and symptoms at follow up. PMID:11157535

A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections

PubMed Central

Gupta, Aditya K; Daigle, Deanne

2016-01-01

Luliconazole is a novel imidazole derivative, which has demonstrated in vitro efficacy against dermatophytes and Candida. The results from Phase III trials show that luliconazole 1% cream applied once daily for 2 weeks successfully resolved the clinical signs and symptoms as well as eradicated the pathologic fungi, which cause tinea pedis. A 1-week treatment with luliconazole 1% cream also produced favorable clinical and mycological results in clinical trials for tinea corporis and tinea cruris. Across trials, adverse events consisted mainly of localized reactions following application. The development of a new antifungal agent is timely due to mounting resistance among existing treatments. Because luliconazole requires a short duration of treatment, it may assist in reducing disease recurrence as a result of patient nonadherence. PMID:26848272

Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and literature review.

PubMed

Zhou, Jie; Chen, Min; Chen, Hongduo; Pan, Weihua; Liao, Wanqing

2014-03-01

Onychomycosis is a common superficial fungal infection, which usually caused by dermatophytes, yeast and non-dermatophytic moulds. Recently, we isolated a Rhodotorula minuta isolate from a 15-year-old immunocompetent girl student in Hangzhou (China) that was identified using microscopy, culture morphology, histological diagnosis, API 20C AUX Yeast Identification Kit and sequencing of the Internal Transcribed Spacer region. In vitro, antifungal susceptibility tests showed that this yeast isolate was susceptible to low concentrations of amphotericin B, itraconazole, voriconazole and 5-flvoriconaz but that it appeared to be dose-dependent susceptible to fluconazole(MIC = 16 μg/ml). Furthermore, the effective result of therapy with itraconazole against R. minuta was consistent with that of susceptibility tests. © 2013 Blackwell Verlag GmbH.

Developing best practice for fungal specimen management: audit of UK microbiology laboratories.

PubMed

Lasseter, G; Palmer, M; Morgan, J; Watts, J; Yoxall, H; Kibbler, C; McNulty, C

2011-01-01

This study represents an audit of microbiology laboratories in the UK to ascertain whether they are aware of, or follow, the Health Protection Agency (HPA) National Standard Methods Standard Operating Procedure (NSM SOP) for the investigation of dermatological specimens for superficial mycoses, or use a locally adapted version. A questionnaire audit was distributed to 179 NHS microbiology laboratories throughout England, Wales, Scotland and Northern Ireland. The NSM SOP was followed by 92% of laboratories for the microscopy of dermatological samples; light microscopy/ KOH digestion was used by 63% and fluorescence microscopy/KOH digestion by 29% of laboratories. Preliminary reports post-microscopy were issued by 98% of laboratories, with 93% issuing reports within 48 hours. Adherence to the NSM SOP guidelines for culture was low; only 34% of laboratories incubated microscopy-negative specimens for the recommended 14 days, while approximately 60% incubated microscopy-positive specimens for 21 days. The culture medium recommended by the NSM SOP was used in 82% of laboratories. Comments were added to culture reports by 51% of laboratories; most were added manually and comments varied between laboratories. Nail samples were the most common sample received from primary care, followed by skin and hair. These results show no significant difference in the rate of microscopy positives versus culture positives. Microscopy and culture are the easiest and cheapest methods available to UK laboratories for the investigation of suspected superficial fungal infections. Although most laboratories included in this audit claimed to follow the NSM SOP for microscopy and culture, these results show that the techniques used vary throughout the UK. To maximise the service provided to primary care, UK laboratories should use standardise methods based on the NSM SOP.

Phototoxic action of light emitting diode in the in vitro viability of Trichophyton rubrum.

PubMed

Amorim, José Cláudio Faria; Soares, Betania Maria; Alves, Orley Araújo; Ferreira, Marcus Vinícius Lucas; Sousa, Gerdal Roberto; Silveira, Lívio de Barros; Piancastelli, André Costa Cruz; Pinotti, Marcos

2012-01-01

Trichophyton rubrum is the most common agent of superficial mycosis of the skin and nails causing long lasting infections and high recurrence rates. Current treatment drawbacks involve topical medications not being able to reach the nail bed at therapeutic concentrations, systemic antifungal drugs failing to eradicate the fungus before the nails are renewed, severe side effects and selection of resistant fungal isolates. Photodynamic therapy (PDT) has been a promising alternative to conventional treatments. This study evaluated the in vitro effectiveness of toluidine blue O (TBO) irradiated by Light emitting diode (LED) in the reduction of T. rubrum viability. The fungal inoculums' was prepared and exposed to different TBO concentrations and energy densities of Light emitting diode for evaluate the T. rubrum sensibility to PDT and production effect fungicidal after photodynamic treatment. In addition, the profiles of the area and volume of the irradiated fungal suspensions were also investigated. A small reduction, in vitro, of fungal cells was observed after exposition to 100 µM toluidine blue O irradiated by 18 J/cm² Light emitting diode. Fungicidal effect occurred after 25 µM toluidine blue O irradiation by Light emitting diode with energy density of 72 J/cm². The analysis showed that the area and volume irradiated by the Light emitting diode were 52.2 mm² and 413.70 mm³, respectively. The results allowed to conclude that Photodynamic therapy using Light emitting diode under these experimental conditions is a possible alternative approach to inhibit in vitro T. rubrum and may be a promising new treatment for dermatophytosis caused by this fungus.

Serious fungal infections in Pakistan.

PubMed

Jabeen, K; Farooqi, J; Mirza, S; Denning, D; Zafar, A

2017-06-01

The true burden of fungal infection in Pakistan is unknown. High-risk populations for fungal infections [tuberculosis (TB), diabetes, chronic respiratory diseases, asthma, cancer, transplant and human immunodeficiency virus (HIV) infection] are numerous. Here, we estimate the burden of fungal infections to highlight their public health significance. Whole and at-risk population estimates were obtained from the WHO (TB), BREATHE study (COPD), UNAIDS (HIV), GLOBOCAN (cancer) and Heartfile (diabetes). Published data from Pakistan reporting fungal infections rates in general and specific populations were reviewed and used when applicable. Estimates were made for the whole population or specific populations at risk, as previously described in the LIFE methodology. Of the 184,500,000 people in Pakistan, an estimated 3,280,549 (1.78%) are affected by a serious fungal infection, omitting all cutaneous infection, oral candidiasis and allergic fungal sinusitis, which we could not estimate. Compared with other countries, the rates of candidaemia (21/100,000) and mucormycosis (14/100,000) are estimated to be very high, and are based on data from India. Chronic pulmonary aspergillosis rates are estimated to be high (39/100,000) because of the high TB burden. Invasive aspergillosis was estimated to be around 5.9/100,000. Fungal keratitis is also problematic in Pakistan, with an estimated rate of 44/100,000. Pakistan probably has a high rate of certain life- or sight-threatening fungal infections.

Epidemiology of fungal infections in liver transplant recipients: a six-year study of a large Brazilian liver transplantation centre.

PubMed

Zicker, Michelle; Colombo, Arnaldo Lopes; Ferraz-Neto, Ben-Hur; Camargo, Luis Fernando Aranha

2011-05-01

Liver transplant seems to be an effective option to prolong survival in patients with end-stage liver disease, although it still can be followed by serious complications. Invasive fungal infections (ifi) are related to high rates of morbidity and mortality. The epidemiology of fungal infections in Brazilian liver transplant recipients is unknown. The aim of this observational and retrospective study was to determine the incidence and epidemiology of fungal infections in all patients who underwent liver transplantation at Albert Einstein Israeli Hospital between 2002-2007. A total of 596 liver transplants were performed in 540 patients. Overall, 77 fungal infections occurred in 68 (13%) patients. Among the 77 fungal infections, there were 40 IFI that occurred in 37 patients (7%). Candida and Aspergillus species were the most common etiologic agents. Candida species accounted for 82% of all fungal infections and for 67% of all IFI, while Aspergillus species accounted for 9% of all fungal infections and for 17% of all IFI. Non-albicans Candida species were the predominant Candida isolates. Invasive aspergillosis tended to occur earlier in the post-transplant period. These findings can contribute to improve antifungal prophylaxis and therapy practices in Brazilian centres.

QUANTIFICATION OF PATHOGENIC FUNGI IN WATER

EPA Science Inventory

The rate of systemic fungal infections in humans has shown a dramatic increase since 1980. Fungal infections are difficult to treat and fungal infection account for a significant proportion of all fatal hospital acquired (nosocomial) infections in the United States. Pathogenic ...

Fungal lectin of Peltigera canina induces chemotropism of compatible Nostoc cells by constriction-relaxation pulses of cyanobiont cytoskeleton.

PubMed

Díaz, Eva Maria; Vicente-Manzanares, Miguel; Sacristan, Mara; Vicente, Carlos; Legaz, Maria-Estrella

2011-10-01

A glycosylated arginase acting as a fungal lectin from Peltigera canina is able to produce recruitment of cyanobiont Nostoc cells and their adhesion to the hyphal surface. This implies that the cyanobiont would develop organelles to motility towards the chemoattractant. However when visualized by transmission electron microscopy, Nostoc cells recently isolated from P. canina thallus do not reveal any motile, superficial organelles, although their surface was covered by small spindles and serrated layer related to gliding. The use of S-(3,4-dichlorobenzyl)isothiourea, blebbistatin, phalloidin and latrunculin A provide circumstantial evidence that actin microfilaments rather than MreB, the actin-like protein from prokaryota, and, probably, an ATPase which develops contractile function similar to that of myosin II, are involved in cell motility. These experimental facts, the absence of superficial elements (fimbriae, pili or flagellum) related to cell movement, and the appearance of sunken cells during of after movement verified by scanning electron microscopy, support the hypothesis that the motility of lichen cyanobionts could be achieved by contraction-relaxation episodes of the cytoskeleton induced by fungal lectin act as a chemoattractant.

Fungal lectin of Peltigera canina induces chemotropism of compatible Nostoc cells by constriction-relaxation pulses of cyanobiont cytoskeleton

PubMed Central

Díaz, Eva Maria; Vicente-Manzanares, Miguel; Sacristan, Mara; Legaz, Maria-Estrella

2011-01-01

A glycosylated arginase acting as a fungal lectin from Peltigera canina is able to produce recruitment of cyanobiont Nostoc cells and their adhesion to the hyphal surface. This implies that the cyanobiont would develop organelles to motility toward the chemoattractant. However when visualized by transmission electron microscopy, Nostoc cells recently isolated from P. canina thallus do not reveal any motile, superficial organelles, although their surface was covered by small spindles and serrated layer related to gliding. The use of S-(3,4-dichlorobenzyl)isothiourea, blebbistatin, phalloidin and latrunculin A provide circumstantial evidence that actin microfilaments rather than MreB, the actin-like protein from prokaryota, and probably, an ATPase which develops contractile function similar to that of myosin II, are involved in cell motility. These experimental facts, the absence of superficial elements (fimbriae, pili or flagellum) related to cell movement, and the appearance of sunken cells during of after movement verified by scanning electron microscopy, support the hypothesis that the motility of lichen cyanobionts could be achieved by contraction-relaxation episodes of the cytoskeleton induced by fungal lectin act as a chemoattractant. PMID:21897128

Invasive fungal infections in Colombian patients with systemic lupus erythematosus.

PubMed

Santamaría-Alza, Y; Sánchez-Bautista, J; Fajardo-Rivero, J F; Figueroa, C L

2018-06-01

Introduction Systemic lupus erythematosus is an autoimmune disease with multi-organ involvement. Complications, such as invasive fungal infections usually occur in patients with a greater severity of the disease. Objective The objective of this study was to determine the prevalence and risk variables associated with invasive fungal infections in a Colombian systemic lupus erythematosus population. Materials and methods A cross-sectional, retrospective study that evaluated patients with systemic lupus erythematosus for six years. The primary outcome was invasive fungal infection. Descriptive, group comparison and bivariate analysis was performed using Stata 12.0 software. Results Two hundred patients were included in this study; 84.5% of the patients were women and the median age was 36 years; 68% of the subjects had haematological complications; 53.3% had nephropathy; 45% had pneumopathy and 28% had pericardial impairment; 7.5% of patients had invasive fungal infections and the most frequently isolated fungus was Candida albicans. Pericardial disease, cyclophosphamide use, high disease activity, elevated ESR, C3 hypocomplementemia, anaemia and lymphopenia had a significant association with invasive fungal infection ( P < 0.05). Conclusions We describe for the first time the prevalence of invasive fungal infection in a Colombian population with systemic lupus erythematosus, which was higher than that reported in other latitudes. In this population the increase in disease activity, the presence of pericardial impairment and laboratory alterations (anaemia, lymphopenia, increased ESR and C3 hypocomplementemia) are associated with a greater possibility of invasive fungal infections. Regarding the use of drugs, unlike other studies, in the Colombian population an association was found only with the previous administration of cyclophosphamide. In addition, patients with invasive fungal infections and systemic lupus erythematosus had a higher prevalence of mortality and hospital readmission compared with patients with systemic lupus erythematosus without invasive fungal infection.

Molecular mechanisms of cryptococcal meningitis

PubMed Central

Liu, Tong-Bao; Perlin, David; Xue, Chaoyang

2012-01-01

Fungal meningitis is a serious disease caused by a fungal infection of the central nervous system (CNS) mostly in individuals with immune system deficiencies. Fungal meningitis is often fatal without proper treatment, and the mortality rate remains unacceptably high even with antifungal drug interventions. Currently, cryptococcal meningitis is the most common fungal meningitis in HIV-1/AIDS, and its disease mechanism has been extensively studied. The key steps for fungi to infect brain and cause meningitis after establishment of local infection are the dissemination of fungal cells to the bloodstream and invasion through the blood brain barrier to reach the CNS. In this review, we use cryptococcal CNS infection as an example to describe the current molecular understanding of fungal meningitis, including the establishment of the infection, dissemination, and brain invasion. Host and microbial factors that contribute to these infection steps are also discussed. PMID:22460646

Human Fungal Pathogens of Mucorales and Entomophthorales.

PubMed

Mendoza, Leonel; Vilela, Raquel; Voelz, Kerstin; Ibrahim, Ashraf S; Voigt, Kerstin; Lee, Soo Chan

2014-11-06

In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known to infect humans. Hence, infections caused by zygomycetes have been called zygomycosis, and the term "zygomycosis" is often used as a synonym for "mucormycosis." In the four-phylum fungal kingdom system, Zygomycota is classified mainly based on morphology, including the ability to form coenocytic (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are 10 known orders, two of which, the Mucorales and Entomophthorales, contain species that can infect humans, and the infection has historically been known as zygomycosis. However, recent multilocus sequence typing analyses (the fungal tree of life [AFTOL] project) revealed that the Zygomycota forms not a monophyletic clade but instead a polyphyletic clade, whereas Ascomycota and Basidiomycota are monophyletic. Thus, the term "zygomycosis" needed to be further specified, resulting in the terms "mucormycosis" and "entomophthoramycosis." This review covers these two different types of fungal infections. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Human Fungal Pathogens of Mucorales and Entomophthorales

PubMed Central

Mendoza, Leonel; Vilela, Raquel; Voelz, Kerstin; Ibrahim, Ashraf S.; Voigt, Kerstin; Lee, Soo Chan

2015-01-01

In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known to infect humans. Hence, infections caused by zygomycetes have been called zygomycosis, and the term “zygomycosis” is often used as a synonym for “mucormycosis.” In the four-phylum fungal kingdom system, Zygomycota is classified mainly based on morphology, including the ability to form coenocytic (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are 10 known orders, two of which, the Mucorales and Entomophthorales, contain species that can infect humans, and the infection has historically been known as zygomycosis. However, recent multilocus sequence typing analyses (the fungal tree of life [AFTOL] project) revealed that the Zygomycota forms not a monophyletic clade but instead a polyphyletic clade, whereas Ascomycota and Basidiomycota are monophyletic. Thus, the term “zygomycosis” needed to be further specified, resulting in the terms “mucormycosis” and “entomophthoramycosis.” This review covers these two different types of fungal infections. PMID:25377138

Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes

PubMed Central

Hiller, Ekkehard; Istel, Fabian; Tscherner, Michael; Brunke, Sascha; Ames, Lauren; Firon, Arnaud; Green, Brian; Cabral, Vitor; Marcet-Houben, Marina; Jacobsen, Ilse D.; Quintin, Jessica; Seider, Katja; Frohner, Ingrid; Glaser, Walter; Jungwirth, Helmut; Bachellier-Bassi, Sophie; Chauvel, Murielle; Zeidler, Ute; Ferrandon, Dominique; Gabaldón, Toni; Hube, Bernhard; d'Enfert, Christophe; Rupp, Steffen; Cormack, Brendan; Haynes, Ken; Kuchler, Karl

2014-01-01

The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes. PMID:24945925

Posaconazole: an extended-spectrum triazole antifungal agent.

PubMed

Schiller, Daryl S; Fung, Horatio B

2007-09-01

The incidence of invasive fungal infections (IFIs) caused by opportunistic filamentous molds is increasing, along with emerging fungal resistance. Posaconazole, a structural analogue of itraconazole that was approved for marketing in the United States in 2006, appears to be a promising antifungal agent. This article provides an overview of the pharmacology, efficacy, and tolerability of posaconazole when used for the prophylaxis and treatment of various common and rare fungal infections. Relevant information was identified through a search of MEDLINE (1966-April 2007), International Pharmaceutical Abstracts (1970-April 2007), and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy using the terms posaconazole and SCH 56592. Additional resources were found by searching the reference lists of the identified articles and the US Food and Drug Administration Web site. Posaconazole is available as an oral suspension. It is highly distributed to various sites, including bone, the central nervous system, and eye tissue. Its Vd is 2447 L when administered in multiple daily doses (up to 800 mg/d) in the presence of a high-fat meal. Because it is excreted mostly as unchanged drug in the feces (77%), posaconazole can be administered to patients with poor renal function without any dose adjustment. Posaconazole has shown in vitro and in vivo activity against a wide variety of fungi, including those that are rare and relatively resistant. Two clinical trials have compared posaconazole with fluconazole or itraconazole for the prophylaxis of IFIs in immunocompromised patients. The first, a randomized, double-blind trial in 600 recipients of hematopoietic stem cell transplants, found that overall rates of IFI did not differ significantly between posaconazole and fluconazole (5% vs 9%, respectively). The other, a randomized, open-label trial in 602 neutropenic patients, reported significantly fewer IFIs in patients receiving posaconazole compared with those receiving fluconazole or itraconazole (>2% vs >8%, respectively; P = 0.001). An additional 2 trials have investigated posaconazole for the treatment of oropharyngeal candidiasis (OPC) in patients with HIV infection. A randomized, controlled, evaluator-blinded study in 350 HIV-infected patients with OPC found similar 14-day clinical success rates with posaconazole and fluconazole (91.7% and 92.5%, respectively; 95% CI, -6.6l to 5.04), whereas an open-label study in 176 HIV-infected patients with a history of refractory OPC reported a 28-day clinical success rate of 75%. Numerous small studies and case reports have described successful posaconazole treatment of zygomycosis, aspergillosis, fusariosis, endemic dimorphic fungal infection, and superficial and subcutaneous fungal infections that were refractory to conventional antifungal agents or in patients who were unable to tolerate these agents. Posaconazole has been well tolerated. The most common complaints have been gastrointestinal in nature, including nausea (7%-8%) and diarrhea (3%-11%), although these have rarely led to permanent discontinuation of therapy. Other common adverse effects have included vomiting (4%-7%), headache (2%-8%), and liver enzyme elevations (2%-3%). Posaconazole suspension administered at up to 800 mg/d is a reasonable alternative to conventional antifungal agents for the prevention and treatment of IFIs in high-risk populations. It may also be suitable in patients with infections caused by rare or relatively resistant fungi, and those who are unable to tolerate long-term therapy with other antifungal agents.

Concepts and Principles of Photodynamic Therapy as an Alternative Antifungal Discovery Platform

PubMed Central

Dai, Tianhong; Fuchs, Beth B.; Coleman, Jeffrey J.; Prates, Renato A.; Astrakas, Christos; St. Denis, Tyler G.; Ribeiro, Martha S.; Mylonakis, Eleftherios; Hamblin, Michael R.; Tegos, George P.

2012-01-01

Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants. PMID:22514547

Clinical risk factors predicting genital fungal infections with sodium-glucose cotransporter 2 inhibitor treatment: The ABCD nationwide dapagliflozin audit.

PubMed

Thong, Ken Yan; Yadagiri, Mahender; Barnes, Dennis Joseph; Morris, David Stuart; Chowdhury, Tahseen Ahmad; Chuah, Ling Ling; Robinson, Anthony Michael; Bain, Stephen Charles; Adamson, Karen Ann; Ryder, Robert Elford John

2018-02-01

Treatment of type 2 diabetes with sodium-glucose cotransporter 2 (SGLT2) inhibitors may result in genital fungal infections. We investigated possible risk factors for developing such infections among patients treated with the SGLT2 inhibitor dapagliflozin. The Association of British Clinical Diabetologists (ABCD) collected data on patients treated with dapagliflozin in routine clinical practice from 59 diabetes centres. We assessed possible associations of patient's age, diabetes duration, body mass index, glycated haemoglobin, renal function, patient sex, ethnicity and prior genital fungal infection, urinary tract infection, urinary incontinence or nocturia, with the occurrence of ≥1 genital fungal infection within 26 weeks of treatment. 1049 out of 1116 patients (476 women, 573 men) were analysed. Baseline characteristics were, mean±SD, age 56.7±10.2years, BMI 35.5±6.9kg/m 2 and HbA 1c 9.4±1.5%. Only patient sex (13.2% women vs 3.3% men) and prior history of genital fungal infection (21.6% vs 7.3%) were found to be associated with occurrence of genital fungal infections after dapagliflozin treatment, adjusted OR 4.22 [95%CI 2.48,7.19], P<0.001 and adjusted OR 2.41 [95% CI 1.04,5.57], P=0.039, respectively. Women and patients with previous genital fungal infections had higher risks of developing genital fungal infections with dapagliflozin treatment. Copyright © 2017 Primary Care Diabetes Europe. All rights reserved.

Uncommon presentations of tinea versicolor

PubMed Central

Varada, Sowmya; Dabade, Tushar; Loo, Daniel S.

2014-01-01

Tinea versicolor (TV) is a common cutaneous fungal infection characterized by superficial scaling and a mild disturbance of skin pigmentation. It typically affects the chest, upper back, and shoulders. However, involvement of more unusual regions of the body such as the face and scalp, arms and legs, intertriginous sites, genitalia, areolae, and palms and soles has been reported. This report details two such cases observed at our institution: a 32-year-old woman with involvement of the popliteal fossa and a 16-year-old boy with involvement of the groin. The clinician must be aware of these variations in location and perform the appropriate diagnostic workup when lesions have the characteristic morphology of TV despite an unusual location. The etiology, pathophysiology, and epidemiology of TV are reviewed and current literature describing other instances of TV in uncommon locations is discussed. PMID:25126470

Yeast central nervous system infection in a critically ill patient: a case report.

PubMed

Frantzeskaki, Frantzeska; Diakaki, Chryssi; Rizos, Michalis; Theodorakopoulou, Maria; Papadopoulos, Panagiotis; Antonopoulou, Anastasia; Nikitas, Nikitas; Lignos, Michail; Brountzos, Elias; Velegraki, Aristea; Paramythiotou, Elisabeth; Panagyotides, John; Armaganidis, Apostolos; Dimopoulos, George

2014-07-15

Invasive fungal infections are alarmingly common in intensive care unit patients; invasive fungal infections are associated with increased morbidity and mortality. Risk factors are the increased use of indwelling central venous catheters, the use of broad spectrum antibiotics, parenteral nutrition, renal replacement therapy and immunosuppression. Diagnosis of these infections might be complicated, requiring tissue cultures. In addition, therapy of invasive fungal infections might be difficult, given the rising resistance of fungi to antifungal agents. We describe the case of a 28-year-old Greek man with yeast central nervous system infection. Difficult-to-treat fungal infections may complicate the clinical course of critically ill patients and render their prognosis unfavorable. This report presents a case that was rare and difficult to treat, along with a thorough review of the investigation and treatment of these kinds of fungal infections in critically ill patients.

Medical mycology and fungal immunology: new research perspectives addressing a major world health challenge

PubMed Central

Gow, Neil A. R.; Netea, Mihai G.

2016-01-01

Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV. To address these global threats to human health, more research is urgently needed to understand the immunopathology of fungal disease and human disease susceptibility in order to augment the advances being made in fungal diagnostics and drug development. Here, we highlight some recent advances in basic research in medical mycology and fungal immunology that are beginning to inform clinical decisions and options for personalized medicine, vaccine development and adjunct immunotherapies. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080988

Medical mycology and fungal immunology: new research perspectives addressing a major world health challenge.

PubMed

Gow, Neil A R; Netea, Mihai G

2016-12-05

Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV. To address these global threats to human health, more research is urgently needed to understand the immunopathology of fungal disease and human disease susceptibility in order to augment the advances being made in fungal diagnostics and drug development. Here, we highlight some recent advances in basic research in medical mycology and fungal immunology that are beginning to inform clinical decisions and options for personalized medicine, vaccine development and adjunct immunotherapies.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Authors.

Advances in the diagnosis and treatment of fungal infections of the CNS.

PubMed

Schwartz, Stefan; Kontoyiannis, Dimitrios P; Harrison, Thomas; Ruhnke, Markus

2018-04-01

Fungal infections of the CNS are challenging to treat and their optimal management requires knowledge of their epidemiology, host characteristics, diagnostic criteria, and therapeutic options. Aspergillus and Cryptococcus species predominate among fungal infections of the CNS. Most of these fungi are ubiquitous, but some have restricted geographical distribution. Fungal infections of the CNS usually originate from primary sites outside the CNS (eg, fungal pneumonia) or occur after inoculation (eg, invasive procedures). Most patients with these infections have immunodeficiencies, but immunocompetent individuals can also be infected through heavy exposure. The infecting fungi can be grouped into moulds, yeasts, and dimorphic fungi. Substantial progress has been made with new diagnostic approaches and the introduction of novel antifungal drugs, but fungal infections of the CNS are frequently lethal because of diagnostic delays, impaired drug penetration, resistance to antifungal treatments, and inadequate restoration of immune function. To improve outcomes, future research should advance diagnostic methods (eg, molecular detection and fungus identification), develop antifungal compounds with enhanced CNS-directed efficacy, and further investigate crucial host defence mechanisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Cutaneous Malassezia infections and Malassezia associated dermatoses: An update].

PubMed

Nenoff, P; Krüger, C; Mayser, P

2015-06-01

The lipophilic yeast fungus Malassezia (M.) spp. is the only fungal genus or species which is part of the physiological human microbiome. Today, at least 14 different Malassezia species are known; most of them can only be identified using molecular biological techniques. As a facultative pathogenic microorganism, Malassezia represents the causative agent both of superficial cutaneous infections and of blood stream infections. Pityriasis versicolor is the probably most frequent infection caused by Malassezia. Less common, Malassezia folliculitis occurs. There is only an episodic report on Malassezia-induced onychomycosis. Seborrhoeic dermatitis represents a Malassezia-associated inflammatory dermatosis. In addition, Malassezia allergenes should be considered as the trigger of "Head-Neck"-type atopic dermatitis. Ketoconazole possesses the strongest in vitro activity against Malassezia, and represents the treatment of choice for topical therapy of pityriasis versicolor. Alternatives include other azole antifungals but also the allylamine terbinafine and the hydroxypyridone antifungal agent ciclopirox olamine. "Antiseborrhoeic" agents, e.g. zinc pyrithione, selenium disulfide, and salicylic acid, are also effective in pityriasis versicolor. The drug of choice for oral treatment of pityriasis versicolor is itraconazole; an effective alternative represents fluconazole. Seborrhoeic dermatitis is best treated with topical medication, including topical corticosteroids and antifungal agents like ketoconazole or sertaconazole. Calcineurin inhibitors, e.g. pimecrolimus and tacrolimus, are reliable in seborrhoeic dermatitis, however are used off-label.

Herbal liposome for the topical delivery of ketoconazole for the effective treatment of seborrheic dermatitis

NASA Astrophysics Data System (ADS)

Dave, Vivek; Sharma, Swati; Yadav, Renu Bala; Agarwal, Udita

2017-11-01

The aim of the present study was to develop liposomal gel containing ketoconazole and neem extract for the treatment of seborrheic dermatitis in an effectual means. Azoles derivatives that are commonly used to prevent superficial fungal infections include triazole category like itraconazole. These drugs are available in the form of oral dosage that required a long period of time for treatment. Ketoconazole is available in the form of gel but is not used with any herbal extract. Neem ( Azadirachta indica) leaves show a good anti-bacterial and anti-fungal activity and have great potential as a bioactive compound. The thin film hydration method was used to design an herbal liposomal preparation. The formulation was further subjected to their characterization as particle size, zeta potential, entrapment efficiency, % cumulative drug release, and anti-fungal activity and it was also characterized by the mean of their physicochemical properties such as FTIR, SEM, DSC, TGA, and AFM. The results show that the formulation of liposomes with neem extract F12 were found to be optimum on the basis of entrapment efficiency in the range 88.9 ± 0.7%, with a desired mean particle size distribution of 141.6 nm and zeta potential - 45 mV. The anti-fungal activity of liposomal formulation F12 was carried out against Aspergillus niger and Candida tropicalis by measuring the inhibition zone 8.9 and 10.2 mm, respectively. Stability of optimized formulation was best seen at refrigerated condition. Overall, these results indicated that developed liposomal gel of ketoconazole with neem extract could have great potential for seborrheic dermatitis and showed synergetic effect for the treatment.

Tissue-Resident Macrophages in Fungal Infections.

PubMed

Xu, Shengjie; Shinohara, Mari L

2017-01-01

Invasive fungal infections result in high morbidity and mortality. Host organs targeted by fungal pathogens vary depending on the route of infection and fungal species encountered. Cryptococcus neoformans infects the respiratory tract and disseminates throughout the central nervous system. Candida albicans infects mucosal tissues and the skin, and systemic Candida infection in rodents has a tropism to the kidney. Aspergillus fumigatus reaches distal areas of the lung once inhaled by the host. Across different tissues in naïve hosts, tissue-resident macrophages (TRMs) are one of the most populous cells of the innate immune system. Although they function to maintain homeostasis in a tissue-specific manner during steady state, TRMs may function as the first line of defense against invading pathogens and may regulate host immune responses. Thus, in any organs, TRMs are uniquely positioned and specifically programmed to function. This article reviews the current understanding of the roles of TRMs during major fungal infections.

Volatiles Emitted from Maize Ears Simultaneously Infected with Two Fusarium Species Mirror the Most Competitive Fungal Pathogen

PubMed Central

Sherif, Mohammed; Becker, Eva-Maria; Herrfurth, Cornelia; Feussner, Ivo; Karlovsky, Petr; Splivallo, Richard

2016-01-01

Along with barley and rice, maize provides staple food for more than half of the world population. Maize ears are regularly infected with fungal pathogens of the Fusarium genus, which, besides reducing yield, also taint grains with toxic metabolites. In an earlier work, we have shown that maize ears infection with single Fusarium strains was detectable through volatile sensing. In nature, infection most commonly occurs with more than a single fungal strain; hence we tested how the interactions of two strains would modulate volatile emission from infected ears. For this purpose, ears of a hybrid and a dwarf maize variety were simultaneously infected with different strains of Fusarium graminearum and F. verticillioides and, the resulting volatile profiles were compared to the ones of ears infected with single strains. Disease severity, fungal biomass, and the concentration of the oxylipin 9-hydroxy octadecadienoic acid, a signaling molecule involved in plant defense, were monitored and correlated to volatile profiles. Our results demonstrate that in simultaneous infections of hybrid and dwarf maize, the most competitive fungal strains had the largest influence on the volatile profile of infected ears. In both concurrent and single inoculations, volatile profiles reflected disease severity. Additionally, the data further indicate that dwarf maize and hybrid maize might emit common (i.e., sesquiterpenoids) and specific markers upon fungal infection. Overall this suggests that volatile profiles might be a good proxy for disease severity regardless of the fungal competition taking place in maize ears. With the appropriate sensitivity and reliability, volatile sensing thus appears as a promising tool for detecting fungal infection of maize ears under field conditions. PMID:27729923

Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib.

PubMed

Ghez, David; Calleja, Anne; Protin, Caroline; Baron, Marine; Ledoux, Marie-Pierre; Damaj, Gandhi; Dupont, Mathieu; Dreyfus, Brigitte; Ferrant, Emmanuelle; Herbaux, Charles; Laribi, Kamel; Le Calloch, Ronan; Malphettes, Marion; Paul, Franciane; Souchet, Laetitia; Truchan-Graczyk, Malgorzata; Delavigne, Karen; Dartigeas, Caroline; Ysebaert, Loïc

2018-04-26

Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present. © 2018 by The American Society of Hematology.

Burden of serious fungal infections in Guatemala.

PubMed

Medina, N; Samayoa, B; Lau-Bonilla, D; Denning, D W; Herrera, R; Mercado, D; Guzmán, B; Pérez, J C; Arathoon, E

2017-06-01

Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.

Invasive fungal infections in pediatric oncology.

PubMed

Mor, Meirav; Gilad, Gil; Kornreich, Liora; Fisher, Salvador; Yaniv, Isaac; Levy, Itzhak

2011-07-01

Data on the epidemiology and outcome of invasive fungal infections in children with cancer are limited. The aim of the study was to delineate the epidemiologic, clinical features, risk factors, and outcome of invasive fungal infections in this population. The medical records of all children with malignancies diagnosed with an invasive fungal infection in 1998-2006 at a tertiary pediatric medical center were reviewed for demographic, clinical, and laboratory data. Invasive fungal infection was diagnosed according to the latest EORTC/MSG criteria. Of the 1,047 children hospitalized in the hematology/oncology department during the study period, 75 (7.2%) were diagnosed with a proven (n = 16, 21.3%), probable (n = 18, 24%), or possible (n= 41, 54.7%) invasive fungal infection. Fifteen (20%) had candidemia (non-albicans in 60%), and 60 (80%) had a mold infection (non-Aspergillus in 55%). Crude mortality was 21.7%. The most common underlying diseases were myeloid leukemia (n = 26, 34.7%) and acute lymphoblastic leukemia (n = 24, 32%). Compared to other malignancies, acute myeloid leukemia was significantly associated with the development of invasive fungal infections. Profound neutropenia and high treatment intensity were present in 89% and 73% of patients with IFI respectively. The current mortality rates of invasive fungal infection in children with cancer are lower than previously reported in children and adults. However, the proportion of non-albicans candidemia is increasing, and non-Aspergillus molds are emerging as important pathogens, which may have important implications for prophylaxis and empiric therapy. Improved prevention, early detection, and advanced treatment strategies are needed to improve the outcome. Copyright © 2011 Wiley-Liss, Inc.

Use of prophylactic voriconazole for three months after lung transplantation does not reduce infection with Aspergillus: a retrospective study of 147 patients.

PubMed

Tofte, Nete; Jensen, Claus; Tvede, Michael; Andersen, Claus B; Carlsen, Jørn; Iversen, Martin

2012-11-01

This was a retrospective study analyzing the mortality and incidence of Aspergillus infection and invasive disease, comparing patients given voriconazole for 3 months following transplantation to patients not given prophylaxis. All consecutive patients (n = 147) transplanted at Copenhagen University Hospital, Rigshospitalet from 2002 to 2006 were included in the study; the study period included the 2 years before the initiation of fungal prophylaxis (88 patients) and the 2 years after (59 patients). Eight patients transplanted in this period were excluded leaving 139 patients in the study. No effect of voriconazole on the incidence of Aspergillus infection (colonization, or superficial or invasive infection) or on the time from transplantation to the first sign of infection was seen when the 2 groups of patients were compared. The cumulated incidence of infection was 45% without and 49% with prophylaxis, and in both groups approximately half of the infections occurred in the first 3 months, the time during which prophylaxis was given. There were significantly more cystic fibrosis (CF) patients among the Aspergillus-infected patients compared to other diagnoses, and the effect of prophylaxis was the same as in non-CF patients. There was a significantly lower mortality in the voriconazole-treated group compared to the non-prophylaxis group, but in an isolated analysis of Aspergillus-infected patients this difference no longer existed; hence, the difference in mortality must be attributable to a time effect and not to voriconazole prophylaxis. Routine use of voriconazole treatment for prophylaxis against Aspergillus infection in lung transplant recipients does not appear to be warranted.

HIF1α-dependent glycolysis promotes macrophage functional activities in protecting against bacterial and fungal infection.

PubMed

Li, Chunxiao; Wang, Yu; Li, Yan; Yu, Qing; Jin, Xi; Wang, Xiao; Jia, Anna; Hu, Ying; Han, Linian; Wang, Jian; Yang, Hui; Yan, Dapeng; Bi, Yujing; Liu, Guangwei

2018-02-26

Macrophages are important innate immune defense system cells in the fight against bacterial and fungal pathogenic infections. They exhibit significant plasticity, particularly with their ability to undergo functional differentiation. Additionally, HIF1α is critically involved in the functional differentiation of macrophages during inflammation. However, the role of macrophage HIF1α in protecting against different pathogenic infections remains unclear. In this study, we investigated and compared the roles of HIF1α in different macrophage functional effects of bacterial and fungal infections in vitro and in vivo. We found that bacterial and fungal infections produced similar effects on macrophage functional differentiation. HIF1α deficiency inhibited pro-inflammatory macrophage functional activities when cells were stimulated with LPS or curdlan in vitro or when mice were infected with L. monocytogenes or C. albicans in vivo, thus decreasing pro-inflammatory TNFα and IL-6 secretion associated with pathogenic microorganism survival. Alteration of glycolytic pathway activation was required for the functional differentiation of pro-inflammatory macrophages in protecting against bacterial and fungal infections. Thus, the HIF1α-dependent glycolytic pathway is essential for pro-inflammatory macrophage functional differentiation in protecting against bacterial and fungal infections.

Prophenoloxidase-Mediated Ex Vivo Immunity to Delay Fungal Infection after Insect Ecdysis.

PubMed

Zhang, Jie; Huang, Wuren; Yuan, Chuanfei; Lu, Yuzhen; Yang, Bing; Wang, Cheng-Yuan; Zhang, Peng; Dobens, Leonard; Zou, Zhen; Wang, Chengshu; Ling, Erjun

2017-01-01

Skin immunity protects animals from airborne pathogen infection. Unlike mammals, arthropods, including insects, undergo periodic ecdysis to grow and develop. Newly molted insects emerge with unsclerotized thin cuticles but successfully escape pathogenic infections during the post-molt period. Here we show that prophenoloxidases (PPOs) in molting fluids remain bioactive on the integument and impede fungal infection after ecdysis. We found that the purified plasma PPOs or recombinant PPOs could effectively bind to fungal spores (conidia) by targeting the cell wall components chitin and β-1,3-glucan. Pretreatment of the spores of the fungal pathogen Beauveria bassiana with PPOs increased spore hydrophilicity and reduced spore adhesion activity, resulting in a significant decrease in virulence as compared with mock infection. We also identified a spore-secreted protease BPS8, a member of peptidase S8 family of protease that degrade PPOs at high levels to benefit fungal infection, but which at lower doses activate PPOs to inhibit spore germination after melanization. These data indicate that insects have evolved a distinct strategy of ex vivo immunity to survive pathogen infections after ecdysis using PPOs in molting fluids retained on the underdeveloped and tender integument of newly molted insects for protection against airborne fungal infection.

Liver fungal infections: an overview of the etiology and epidemiology in patients affected or not affected by oncohematologic malignancies

PubMed Central

Bimonte, Sabrina; Maraolo, Alberto Enrico; Gentile, Ivan; Schiavone, Vincenzo; Pace, Maria Caterina

2018-01-01

Fungal infections of the liver, most commonly caused by Candida spp., often occur in patients with hematologic malignancies treated with chemotherapy. Colonization of the gastrointestinal tract is thought to be the main origin of dissemination of Candida; mucositis and neutropenia facilitate the spread of Candida from the gastrointestinal tract to the liver. Hepatic involvement due to other fungi is a less common infectious complication in this setting. Fungal infections represent a less common cause of hepatic abscesses in non-oncohematologic population and the trend appears to be decreasing in recent years. Understanding of the etiology and epidemiology of fungal infections of the liver is indicated for an appropriate antimicrobial therapy and an overall optimal management of fungal liver infections. PMID:29416363

Invasive fungal infections during the neonatal period: diagnosis, treatment and prophylaxis.

PubMed

Tezer, Hasan; Canpolat, Fuat Emre; Dilmen, Uğur

2012-02-01

The incidence of preterm births seems to be increased in many countries around the world, in parallel to the advances in neonatal medicine. However, this has resulted in longer hospital stays and more exposure to invasive interventions, both of which can lead to an increase in late-onset nosocomial infections in the newborn period. In addition to bacteria, fungi are thought to be an important cause of hospital infections. The present article reviews the diagnosis, treatment and prophylaxis of invasive fungal infections (IFIs) during the neonatal period. IFIs are associated with high morbidity and mortality in preterm neonates. The main risk factors are multiple antibiotics, central venous catheters, parenteral nutrition, immunodepression, very low birth weight, and fungal colonization. Successful management of IFIs relies on early recognition and rapid initiation of effective treatment. Invasive-fungal-infection-related morbidity and mortality is a major concern for most neonatal intensive care units worldwide. Incidence rates are increasing for preterm neonates. Preterm infants display clinical characteristics that make them prone to fungal infections, and there is a high frequency of neurodevelopmental sequelae in those who survive after neonatal fungal infections. Specific prevention - rather than treatment - should be the optimal strategy. Both fluconazole and nystatin prophylaxis reduce the incidence of IFI and fungal colonization in very preterm infants.

Fungal infections in children in the early postoperative period after cardiac surgery for congenital heart disease: a single-centre experience.

PubMed

Jaworski, Radoslaw; Haponiuk, Ireneusz; Irga-Jaworska, Ninela; Chojnicki, Maciej; Steffens, Mariusz; Paczkowski, Konrad; Zielinski, Jacek

2016-09-01

Postoperative infections are still an important problem in cardiac surgery, especially in the paediatric population, and may influence the final outcome of congenital heart disease treatment. Postoperative infections with fungi are uncommon. The aetiology is poorly understood, and the proper diagnosis and treatment is unclear. In this single-centre study, the frequency of invasive fungal disease in children who underwent surgical management of congenital heart diseases was determined along with the risk factors for infection, treatment options and outcomes. All consecutive paediatric patients (<18 years of age) who underwent cardiac surgery for congenital heart disease between September 2008 and December 2015 in a paediatric cardiac centre in Poland were identified. Those who developed invasive fungal disease in the early postoperative period (30 days) were identified. Of the 1540 cardiosurgical procedures for congenital heart disease, 6 were complicated by fungal infection (0.39%). One patient had a high probability of fungal infection, but the diagnosis was unproved. Nevertheless, the patient was successfully treated with antifungal treatment. Five had proven invasive fungal disease. Of these, 3 were diagnosed with candidaemia. All had undergone cardiopulmonary bypass. Of the remaining 2 patients, 1 was a preterm newborn with complete atrioventricular septal defect who developed rib fungal invasion. The remaining patient had pulmonary atresia with ventricular septal defect and developed Fournier's gangrene after surgery. None of the patients died due to infection in the early postoperative period. However, the child with rib fungal invasion died 39 days after surgery as a result of multiorgan failure. Fungal infections in paediatric patients after cardiac surgery may markedly influence morbidity and mortality. Fungal infection prophylaxis in this specific group of children may reduce morbidity, whereas early empirical treatment followed by a targeted approach may improve outcomes. The 'hit fast, hit hard' treatment strategy may be the best rescue option for children who develop invasive fungal disease after cardiac surgery. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Monitoring fungal growth on brown rice grains using rapid and non-destructive hyperspectral imaging.

PubMed

Siripatrawan, U; Makino, Y

2015-04-16

This research aimed to develop a rapid, non-destructive, and accurate method based on hyperspectral imaging (HSI) for monitoring spoilage fungal growth on stored brown rice. Brown rice was inoculated with a non-pathogenic strain of Aspergillus oryzae and stored at 30 °C and 85% RH. Growth of A. oryzae on rice was monitored using viable colony counts, expressed as colony forming units per gram (CFU/g). The fungal development was observed using scanning electron microscopy. The HSI system was used to acquire reflectance images of the samples covering the visible and near-infrared (NIR) wavelength range of 400-1000 nm. Unsupervised self-organizing map (SOM) was used to visualize data classification of different levels of fungal infection. Partial least squares (PLS) regression was used to predict fungal growth on rice grains from the HSI reflectance spectra. The HSI spectral signals decreased with increasing colony counts, while conserving similar spectral pattern during the fungal growth. When integrated with SOM, the proposed HSI method could be used to classify rice samples with different levels of fungal infection without sample manipulation. Moreover, HSI was able to rapidly identify infected rice although the samples showed no symptoms of fungal infection. Based on PLS regression, the coefficient of determination was 0.97 and root mean square error of prediction was 0.39 log (CFU/g), demonstrating that the HSI technique was effective for prediction of fungal infection in rice grains. The ability of HSI to detect fungal infection at early stage would help to prevent contaminated rice grains from entering the food chain. This research provides scientific information on the rapid, non-destructive, and effective fungal detection system for rice grains. Copyright © 2015 Elsevier B.V. All rights reserved.

Automated in vivo identification of fungal infection on human scalp using optical coherence tomography and machine learning

NASA Astrophysics Data System (ADS)

Dubey, Kavita; Srivastava, Vishal; Singh Mehta, Dalip

2018-04-01

Early identification of fungal infection on the human scalp is crucial for avoiding hair loss. The diagnosis of fungal infection on the human scalp is based on a visual assessment by trained experts or doctors. Optical coherence tomography (OCT) has the ability to capture fungal infection information from the human scalp with a high resolution. In this study, we present a fully automated, non-contact, non-invasive optical method for rapid detection of fungal infections based on the extracted features from A-line and B-scan images of OCT. A multilevel ensemble machine model is designed to perform automated classification, which shows the superiority of our classifier to the best classifier based on the features extracted from OCT images. In this study, 60 samples (30 fungal, 30 normal) were imaged by OCT and eight features were extracted. The classification algorithm had an average sensitivity, specificity and accuracy of 92.30, 90.90 and 91.66%, respectively, for identifying fungal and normal human scalps. This remarkable classifying ability makes the proposed model readily applicable to classifying the human scalp.

Who Gets Fungal Infections?

MedlinePlus

... can also happen in people without weak immune systems Fungal infections that are not life-threatening, such ... to cause an infection. People with weak immune systems Infections that happen because a person’s immune system ...

Clinical study of Tinea capitis in Northern Karnataka: A three-year experience at a single institute.

PubMed

Pai, Varadraj V; Hanumanthayya, Keloji; Tophakhane, Raghavendra S; Nandihal, Namrata W; Kikkeri, Narayan Shetty Naveen

2013-01-01

Tinea capitis is a superficial fungal infection of the hair follicle of scalp. Most of the dermatophytosis do not have such age propensity as tinea capitis which almost invariably involves the paediatric age group. The exact incidence of tinea capitis is not known. This study is done in order to isolate the species variation in an area, to know the changing patterns of occurrence of different species and their association with clinical pattern All clinically diagnosed cases of tinea capitis which presented to our out patient department over a period of one year were included in the study. 70 cases of Tinea capitis were studied. Tinea capitis is a disease of prepubertal children with common in age group of 5- 15 years. The incidence varies from 0.5% to 10%. Most common presenting feature was alopecia.

Clinical study of Tinea capitis in Northern Karnataka: A three-year experience at a single institute

PubMed Central

Pai, Varadraj V.; Hanumanthayya, Keloji; Tophakhane, Raghavendra S.; Nandihal, Namrata W.; Kikkeri, Narayan Shetty Naveen

2013-01-01

Background: Tinea capitis is a superficial fungal infection of the hair follicle of scalp. Most of the dermatophytosis do not have such age propensity as tinea capitis which almost invariably involves the paediatric age group. The exact incidence of tinea capitis is not known. This study is done in order to isolate the species variation in an area, to know the changing patterns of occurrence of different species and their association with clinical pattern Materials and Methods: All clinically diagnosed cases of tinea capitis which presented to our out patient department over a period of one year were included in the study. Results: 70 cases of Tinea capitis were studied. Discussion: Tinea capitis is a disease of prepubertal children with common in age group of 5- 15 years. The incidence varies from 0.5% to 10%. Most common presenting feature was alopecia. PMID:23439970

Pityriasis versicolor in primary school children in Medan Labuhan

NASA Astrophysics Data System (ADS)

Febriyanti; Paramita, DA; Eyanoer, P.

2018-03-01

Personal hygiene is an activity in which done by someone, directly and indirectly, to keep healthy to prevent the risk of diseases. Personal hygiene is also a factor that plays a role in the occurrence of skin diseases and one of them is Pityriasis versicolor. Pityriasis versicolor is a superficial fungal infection caused by Malassezia furfur which is a saprophytic organism in the skin. Activation of M. furfur into a pathogenic form due to changes in the normal flora of the skin that caused by several factors and one of them is poor personal hygiene. A cross-sectional study consist of 115 eligible students is done to determine the relationship between personal hygiene with the occurrence of Pityriasis versicolor among students in primary school in Medan Labuhan district. The result showed that 59.8% of the subject with poor personal hygiene and there is a significant association between personal hygiene with Pityriasis versicolor (p<0.05).

Improved Survival with Aggressive Surgical Management of Noncandidal Fungal Infections of the Burn Wound

DTIC Science & Technology

1982-10-01

noncandidal fungal infections were diagnosed premor- Mortality of burn patients with fungal infections diagnosed teni . This compares with 63.6" of...pathogenesis, Candida infec- cemia, illustrated evalual ion of its skin lesion . Arch. Intern. Med..128: 591-595, 1971.tions are never discovered when they are

Miconazole therapy for treatment of fungal infections in cancer patients.

PubMed

Jordan, W M; Bodey, G P; Rodriguez, V; Ketchel, S J; Henney, J

1979-12-01

The effectiveness of miconazole was evaluated in 37 documented fungal infections, 32 of which were major infections. All patients were receiving therapy for advanced malignancy, with 28 patients having acute leukemia. The overall cure rate was 41% and it was also 41% for major fungal infections. Nine of 22 patients with Candida albicans infections were cured, and 3 of 11 patients with Candida tropicalis infections were cured. A total of 183 patients who received miconazole for presumed or documented fungal infection were evaluated for toxicity. Nausea and vomiting and central nervous system toxicity were the most common side effects, occurring in 25 and 16% of the patients, respectively. Overall, the drug was tolerated well, with only four patients requiring the drug to be permanently discontinued because of toxicity.

[From guinea pig to man: Tinea outbreak due to Trichophyton mentagrophytes var. porcellae in pet shops in Nancy (France)].

PubMed

Bloch, M; Cavignaux, R; Debourgogne, A; Dorin, J; Machouart, M; Contet-Audonneau, N

2016-09-01

Dermatophytes are responsible for widespread superficial fungal infections, currently representing a real public health problem. Some of the fungi involved in these mycoses are transmitted by pets, illustrating great host specificity within this fungal group. Thus, a new variety of zoophilic dermatophyte has been described in recent years by the Mycology Laboratory of the University Hospital of Nancy, within the complex T. mentagrophytes. This variant was named T. mentagrophytes var. porcellae, following the observation of a significant number of patients with dermatomycoses of exposed parts of the body and having had contact with a guinea pig. The current work follows this first description and aims to assess the frequency of T. mentagrophytes var. porcellae in guinea pigs within three pet shops in the region of Nancy (France). In total, almost two thirds of collected guinea pigs were carriers of this new dermatophyte. This study highlights the risks associated with the adaptation of dermatophytes to potential new hosts that may spread to new species. Thus, in this context, sanitary measures could be proposed to the pet shops, usually not informed of the risks facing the growing enthusiasm of the population for new pets, in order to limit contamination. Copyright © 2016. Published by Elsevier Masson SAS.

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

PubMed Central

Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram

2014-01-01

Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895

Estimation of the Burden of Serious Human Fungal Infections in Malaysia

PubMed Central

Velayuthan, Rukumani Devi; Samudi, Chandramathi; Lakhbeer Singh, Harvinder Kaur; Ng, Kee Peng

2018-01-01

Fungal infections (mycoses) are likely to occur more frequently as ever-increasingly sophisticated healthcare systems create greater risk factors. There is a paucity of systematic data on the incidence and prevalence of human fungal infections in Malaysia. We conducted a comprehensive study to estimate the burden of serious fungal infections in Malaysia. Our study showed that recurrent vaginal candidiasis (>4 episodes/year) was the most common of all cases with a diagnosis of candidiasis (n = 501,138). Oesophageal candidiasis (n = 5850) was most predominant among individuals with HIV infection. Candidemia incidence (n = 1533) was estimated in hospitalized individuals, some receiving treatment for cancer (n = 1073), and was detected also in individuals admitted to intensive care units (ICU) (n = 460). In adults with asthma, allergic bronchopulmonary aspergillosis (ABPA) was the second most common respiratory mycoses noticed (n = 30,062) along with severe asthma with fungal sensitization (n = 39,628). Invasive aspergillosis was estimated in 184 cases undergoing anti-cancer treatment and 834 ICU cases. Cryptococcal meningitis was diagnosed in 700 subjects with HIV/AIDS and Pneumocystis jirovecii pneumonitis (PCP) in 1286 subjects with underlying HIV disease. The present study indicates that at least 590,214 of the Malaysian population (1.93%) is affected by a serious fungal infection annually. This problem is serious enough to warrant the further epidemiological studies to estimate the burden of human fungal infections in Malaysia. PMID:29562712

Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods

PubMed Central

Enguita, Francisco J.; Costa, Marina C.; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José; Leitão, Ana Lúcia

2016-01-01

Fungal invasive infections are an increasing health problem. The intrinsic complexity of pathogenic fungi and the unmet clinical need for new and more effective treatments requires a detailed knowledge of the infection process. During infection, fungal pathogens are able to trigger a specific transcriptional program in their host cells. The detailed knowledge of this transcriptional program will allow for a better understanding of the infection process and consequently will help in the future design of more efficient therapeutic strategies. Simultaneous transcriptomic studies of pathogen and host by high-throughput sequencing (dual RNA-seq) is an unbiased protocol to understand the intricate regulatory networks underlying the infectious process. This protocol is starting to be applied to the study of the interactions between fungal pathogens and their hosts. To date, our knowledge of the molecular basis of infection for fungal pathogens is still very limited, and the putative role of regulatory players such as non-coding RNAs or epigenetic factors remains elusive. The wider application of high-throughput transcriptomics in the near future will help to understand the fungal mechanisms for colonization and survival, as well as to characterize the molecular responses of the host cell against a fungal infection. PMID:29376924

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

PubMed

Hong, Gina; White, Marissa; Lechtzin, Noah; West, Natalie E; Avery, Robin; Miller, Heather; Lee, Richard; Lovari, Robert J; Massire, Christian; Blyn, Lawrence B; Liang, Xinglun; Sutton, Deanna A; Fu, Jianmin; Wickes, Brian L; Wiederhold, Nathan P; Zhang, Sean X

2017-03-01

Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Fungal infection in neural tissue of patients with amyotrophic lateral sclerosis.

PubMed

Alonso, Ruth; Pisa, Diana; Fernández-Fernández, Ana M; Rábano, Alberto; Carrasco, Luis

2017-12-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and the main cause of motor neuron pathology. The etiology of the disease remains unknown, and no effective therapy exists to halt the disease or improve the quality of life. Here, we provide compelling evidence for the existence of fungal infection in ALS. Immunohistochemistry analysis using a battery of antifungal antibodies revealed fungal structures such as yeast and hyphae in the motor cortex, the medulla and the spinal cord, in eleven patients with ALS. Some fungal structures were localized intracellularly and even intranuclearly, indicating that this infection is not the result of post-mortem colonization. By contrast, this burden of fungal infection cannot be observed in several CNS areas of control subjects. PCR analysis and next generation sequencing of DNA extracted from frozen neural tissue identified a variety of fungal genera including Candida, Malassezia, Fusarium, Botrytis, Trichoderma and Cryptococcus. Overall, our present observations provide strong evidence for mixed fungal infections in ALS patients. The exact mixed infection varies from patient to patient consistent with the different evolution and severity of symptoms in each ALS patient. These novel findings provide a logical explanation for the neuropathological observations of this disease, such as neuroinflammation and elevated chitinase levels, and could help to implement appropriate therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Fungal infections and treatment in cystic fibrosis.

PubMed

Middleton, Peter G; Chen, Sharon C-A; Meyer, Wieland

2013-11-01

This review summarizes some of the important recent findings concerning fungal airway infections in patients with cystic fibrosis (CF). For many years, both researchers and clinicians have focused on the problems in CF caused by chronic bacterial airway infection with organisms such as Haemophilus, Staphylococcus and Pseudomonas. However, until recently, the lack of sensitive culture techniques to isolate fungi in sputum, bronchoalveolar lavage fluid and other respiratory tract samples has limited the recognition of fungal species and their possible role in CF airway infections. Recent studies using fungal-selective culture media and molecular techniques have shown a plethora of different fungal species in the sputum expectorated from CF patients. Cross-sectional studies have shown associations between Aspergillus and Candida in the sputum and worse lung function. The presence of allergic bronchopulmonary aspergillosis is likely to be a negative prognostic factor, but whether simple fungal colonization itself indicates future problems is not clear. Current research is now examining these epidemiological associations to try to determine the clinical implications. This will help determine whether fungal colonization/infection is associated with worse outcome in CF patients. At present, there is no conclusive evidence that fungal organisms cause respiratory decline. Recent studies of antifungal therapy in CF patients have reported differing results, so further investigations in this area are needed.

Co-incidental Plasmodium Knowlesi and Mucormycosis infections presenting with acute kidney injury and lower gastrointestinal bleeding.

PubMed

Ramaswami, Arunachalam; Pisharam, Jayakrishnan K; Aung, Hla; Ghazala, Kafeel; Maboud, Khalil; Chong, Vui Heng; Tan, Jackson

2013-01-01

Plasmodium knowlesi is frequently reported in Southeast Asian countries and is now widely regarded as the fifth malarial parasite. Mucormycosis is a rare fungal infection that can occur in patients with a weakened immune system. We report a case of acute kidney injury secondary to Plasmodium knowlesi malaria infection and mucormycosis fungal infection. In addition, the patient also had lower gastrointestinal bleeding from invasive gastrointestinal mucormycosis. P. knowlesi infection was diagnosed by blood film and mucormycosis was diagnosed by histopathological examination of biopsy specimen of the colon. The patient recovered with antimalarial treatment (Quinine), antifungal treatment (Lipophilic Amphotericin), and supportive hemodialysis treatment. We hypothesize that P. knowlesi malarial infection can lower the immunologic threshold and predisposes vulnerable individuals to rare disseminated fungal infections. To the best of our knowledge, this is the first P. Knowlesi malaria-associated invasive fungal infection reported in the literature.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS.

PubMed

Pereira, Graziella Hanna; Lanzoni, Valéria Pereira Barbosa; Beirão, Elisa Maria; Timerman, Artur; Melhem, Marcia de Souza Carvalho

2015-12-01

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

PubMed Central

PEREIRA, Graziella Hanna; LANZONI, Valéria Pereira Barbosa; BEIRÃO, Elisa Maria; TIMERMAN, Artur; MELHEM, Marcia de Souza Carvalho

2015-01-01

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes. PMID:27049710

The fungus Trichophyton redellii sp. nov. causes skin infections that resemble white-nose syndrome of hibernating bats

Treesearch

Jeffrey M. Lorch; Andrew M. Minnis; Carol U. Meteyer; Jennifer A. Redell; J. Paul White; Heather M. Kaarakka; Laura K. Muller; Daniel L. Lindner; Michelle L. Verant; Valerie Shearn-Bochsler; David S. Blehert

2015-01-01

Before the discovery of white-nose syndrome (WNS), a fungal disease caused by Pseudogymnoascus destructans, there were no reports of fungal skin infections in bats during hibernation. In 2011, bats with grossly visible fungal skin infections similar in appearance to WNS were reported from multiple sites in Wisconsin, US, a state outside the known...

Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen Mucor circinelloides in Innate Granulomas In Vivo.

PubMed

Inglesfield, Sarah; Jasiulewicz, Aleksandra; Hopwood, Matthew; Tyrrell, James; Youlden, George; Mazon-Moya, Maria; Millington, Owain R; Mostowy, Serge; Jabbari, Sara; Voelz, Kerstin

2018-03-27

Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modeled by a combined in silico modeling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivo In silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients. IMPORTANCE Mucormycosis is a dramatic fungal infection frequently leading to the death of patients. We know little about the immune response to the fungus causing this infection, although evidence points toward defects in early immune events after infection. Here, we dissect this early immune response to infectious fungal spores. We show that specialized white blood cells (phagocytes) rapidly respond to these spores and accumulate around the fungus. However, we demonstrate that the mechanisms that enable phagocytes to kill the fungus fail, allowing for survival of spores. Instead a cluster of phagocytes resembling an early granuloma is formed around spores to control the latent infection. This study is the first detailed analysis of early granuloma formation during a fungal infection highlighting a latent stage that needs to be considered for clinical management of patients. Copyright © 2018 Inglesfield et al.

Fungal infections in burns: a comprehensive review

PubMed Central

Struck, M.F.; Gille, J.

2013-01-01

Summary Burn wound infections remain the most important factor limiting survival in burn intensive care units. Large wound surface, impaired immune systems, and broad-spectrum antibiotic therapy contribute to the growth of opportunistic fungal species. Faced with challenging fluid resuscitation, wound excision and cardiopulmonary stabilization, mycosis in burns are likely to be underestimated. Diagnostic performance can sometimes be delayed because clinical signs are unspecific and differentiation between colonization and infection is difficult. Therapeutic measures range from infection prophylaxis over treatment with antifungal agents towards radical amputation of infected limbs. New methods of early and reliable detection of fungal organisms, as well as the use of novel antifungal substances, are promising but require wider establishment to confirm the beneficial effects in burn patients. This review aims to highlight the main important aspects of fungal infections in burns including incidence, infection control, diagnostic and therapeutic approaches, prognosis and outcomes. PMID:24563641

Characterization and Molecular Epidemiology of a Fungal Infection of Edible Crabs (Cancer pagurus) and Interaction of the Fungus with the Dinoflagellate Parasite Hematodinium

PubMed Central

Smith, Amanda L.; Hamilton, Kristina M.; Hirschle, Lucy; Wootton, Emma C.; Vogan, Claire L.; Pope, Edward C.; Eastwood, Daniel C.

2013-01-01

This study reports on an emerging fungal disease of the edible crab, Cancer pagurus. Juvenile (prerecruit) crabs were found to be subject to this disease condition during the months of May to September at two intertidal sites in South Wales, United Kingdom. Histopathology revealed that the fungi overwhelm the host response in the tissues, leading to progressive septicemia. The causative agent of this infection was isolated and grown in pure culture and was identified as a member of the Ophiocordyceps clade by sequencing of the small subunit of the fungal ribosomal DNA (rDNA). Of the crabs naturally infected with the fungus, 94% had a coinfection with the parasitic dinoflagellate Hematodinium species. To determine if there was any interaction between the two disease-causing agents, apparently fungus-free crabs, both with and without natural Hematodinium infections, were challenged with the fungal isolate. The presence of Hematodinium caused a significant reduction in fungal multiplication in the hemocoel of the crabs in comparison to that in Hematodinium-free individuals. Histopathology of coinfected crabs showed a systemic multiplication of Hematodinium within host tissues, leading to a rapid death, while Hematodinium-free crabs experimentally infected with the fungal isolate died due to fungal sepsis (septicemia) with the same characteristic pathology as seen in natural infections. PMID:23160130

The protective role of immunoglobulins in fungal infections and inflammation.

PubMed

Elluru, Sri Ramulu; Kaveri, Srini V; Bayry, Jagadeesh

2015-03-01

Increased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg.

Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques.

PubMed

Czurda, Stefan; Lion, Thomas

2017-01-01

Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.

Analysis of whitefly transcriptional responses to Beauveria bassiana infection reveals new insights into insect-fungus interactions.

PubMed

Xia, Jun; Zhang, Chang-Rong; Zhang, Shan; Li, Fang-Fang; Feng, Ming-Guang; Wang, Xiao-Wei; Liu, Shu-Sheng

2013-01-01

The fungal pathogen, Beauveria bassiana, is an efficient biocontrol agent against a variety of agricultural pests. A thorough understanding of the basic principles of insect-fungus interactions may enable the genetic modification of Beauveria bassiana to enhance its virulence. However, the molecular mechanism of insect response to Beauveria bassiana infection is poorly understood, let alone the identification of fungal virulent factors involved in pathogenesis. Here, next generation sequencing technology was applied to examine the expression of whitefly (Bemisia tabaci) genes in response to the infection of Beauveria bassiana. Results showed that, compared to control, 654 and 1,681genes were differentially expressed at 48 hours and 72 hours post-infected whiteflies, respectively. Functional and enrichment analyses indicated that the DNA damage stimulus response and drug metabolism were important anti-fungi strategies of the whitefly. Mitogen-activated protein kinase (MAPK) pathway was also likely involved in the whitefly defense responses. Furthermore, the notable suppression of general metabolism and ion transport genes observed in 72 hours post-infected B. tabaci might be manipulated by fungal secreted effectors. By mapping the sequencing tags to B. bassiana genome, we also identified a number of differentially expressed fungal genes between the early and late infection stages. These genes are generally associated with fungal cell wall synthesis and energy metabolism. The expression of fungal cell wall protein genes might play an important role in fungal pathogenesis and the dramatically up-regulated enzymes of carbon metabolism indicate the increasing usage of energy during the fungal infection. To our knowledge, this is the first report on the molecular mechanism of fungus-whitefly interactions. Our results provide a road map for future investigations on insect-pathogen interactions and genetically modifying the fungus to enhance its efficiency in whitefly control.

Uncommon opportunistic fungal infections of oral cavity: A review

PubMed Central

Deepa, AG; Nair, Bindu J; Sivakumar, TT; Joseph, Anna P

2014-01-01

The majority of opportunistic oral mucosal fungal infections are due to Candida albicans and Aspergillus fumigatus species. Mucor and Cryptococcus also have a major role in causing oral infections, whereas Geotrichum, Fusarium, Rhodotorula, Saccharomyces and Penicillium marneffei are uncommon pathogens in the oral cavity. The broad spectrum of clinical presentation includes pseudo-membranes, abscesses, ulcers, pustules and extensive tissue necrosis involving bone. This review discusses various uncommon opportunistic fungal infections affecting the oral cavity including their morphology, clinical features and diagnostic methods. PMID:25328305

A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.

PubMed

Doria, Cataldo; Bodzin, Adam S; Vaccino, Silvia; Daskalakis, Constantine; Krawitz, Steven; Ramirez, Carlo B

2011-01-01

This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high-risk patients. Post-transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re-transplantation; (ii) re-operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re-intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two-thirds male and three-quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment comparable (p = 0.540), and both better than no preventive treatment at all (OR = 0.15, p = 0.049, for caspofungin versus no preventive treatment; OR = 0.29, p = 0.085, for other antifungal versus no preventive treatment). Caspofungin appears to be an effective preventive agent against fungal infections when used in recipients of liver transplant designated as high risk for fungal infection. Usage of caspofungin in these patients does not carry an apparent increase in risk of death or acute cellular rejection, although we observed a significantly higher risk of AEs, especially acute renal failure (p = 0.001), in patients who received this agent. © 2010 John Wiley & Sons A/S.

Econazole-releasing porous space maintainers for fungal periprosthetic joint infection.

PubMed

Tatara, Alexander M; Rozich, Allison J; Kontoyiannis, Panayiotis D; Watson, Emma; Albert, Nathaniel D; Bennett, George N; Mikos, Antonios G

2018-05-11

While antibiotic-eluting polymethylmethacrylate space maintainers have shown efficacy in the treatment of bacterial periprosthetic joint infection and osteomyelitis, antifungal-eluting space maintainers are associated with greater limitations for treatment of fungal musculoskeletal infections including limited elution concentration and duration. In this study, we have designed a porous econazole-eluting space maintainer capable of greater inhibition of fungal growth than traditional solid space maintainers. The eluted econazole demonstrated bioactivity in a concentration-dependent manner against the most common species responsible for fungal periprosthetic joint infection as well as staphylococci. Lastly, these porous space maintainers retain compressive mechanical properties appropriate to maintain space before definitive repair of the joint or bony defect.

An estimation of burden of serious fungal infections in France.

PubMed

Gangneux, J-P; Bougnoux, M-E; Hennequin, C; Godet, C; Chandenier, J; Denning, D W; Dupont, B

2016-12-01

An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Absidia corymbifera fungal infection in burns: a case report and review of the literature.

PubMed

Constantinides, Joannis; Misra, Alok; Nassab, Reza; Wilson, Yvonne

2008-01-01

Fungal infection in burn wounds can be difficult to diagnose and manage. A previously reported 10-year experience in burns patients confirms that although a marked decline has occurred in bacterial infection, fungal wound infection rates remain unaffected. Moreover, there is significant morbidity and mortality associated with fungal infections in patients with extensive burns. Absidia corymbifera is a saprophytic organism, with worldwide distribution, that is primarily isolated from soil as well as decaying vegetation and grass. It is an uncommon pathogen representing only 2 to 3% of all zygomycete infections in humans. The organism is opportunistic, rarely infecting the immunocompetent although such cases have been reported. To our knowledge, there are only two prior reports of A. corymbifera in burns patients. The ability to invade intact skin through proteolytic enzymes as well as the organism's angioinvasive propensity is associated with high mortality and demands a multidisciplinary approach. We present a case report of A. corymbifera infection in a burns patient and review the current literature.

Crossover fungal pathogens: the biology and pathogenesis of fungi capable of crossing kingdoms to infect plants and humans.

PubMed

Gauthier, Gregory M; Keller, Nancy P

2013-12-01

The outbreak of fungal meningitis associated with contaminated methylprednisolone acetate has thrust the importance of fungal infections into the public consciousness. The predominant pathogen isolated from clinical specimens, Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous fungus that infects grasses and rarely humans. This outbreak highlights the potential for fungal pathogens to infect both plants and humans. Most crossover or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota and Mucormycotina phyla. To establish infection, crossover fungi must overcome disparate, host-specific barriers, including protective surfaces (e.g. cuticle, skin), elevated temperature, and immune defenses. This review illuminates the underlying mechanisms used by crossover fungi to cause infection in plants and mammals, and highlights critical events that lead to human infection by these pathogens. Several genes including veA, laeA, and hapX are important in regulating biological processes in fungi important for both invasive plant and animal infections. Copyright © 2013 Elsevier Inc. All rights reserved.

Impact of operative time on early joint infection and deep vein thrombosis in primary total hip arthroplasty.

PubMed

Wills, B W; Sheppard, E D; Smith, W R; Staggers, J R; Li, P; Shah, A; Lee, S R; Naranje, S M

2018-03-22

Infections and deep vein thrombosis (DVT) after total hip arthroplasty (THA) are challenging problems for both the patient and surgeon. Previous studies have identified numerous risk factors for infections and DVT after THA but have often been limited by sample size. We aimed to evaluate the effect of operative time on early postoperative infection as well as DVT rates following THA. We hypothesized that an increase in operative time would result in increased odds of acquiring an infection as well as a DVT. We conducted a retrospective analysis of prospectively collected data using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2015 for all patients undergoing primary THA. Associations between operative time and infection or DVT were evaluated with multivariable logistic regressions controlling for demographics and several known risks factors for infection. Three different types of infections were evaluated: (1) superficial surgical site infection (SSI), an infection involving the skin or subcutaneous tissue, (2) deep SSI, an infection involving the muscle or fascial layers beneath the subcutaneous tissue, and (3) organ/space infection, an infection involving any part of the anatomy manipulated during surgery other than the incisional components. In total, 103,044 patients who underwent THA were included in our study. Our results suggested a significant association between superficial SSIs and operative time. Specifically, the adjusted odds of suffering a superficial SSI increased by 6% (CI=1.04-1.08, p<0.0001) for every 10-minute increase of operative time. When using dichotomized operative time (<90minutes or >90minutes), the adjusted odds of suffering a superficial SSI was 56% higher for patients with prolonged operative time (CI=1.05-2.32, p=0.0277). The adjusted odds of suffering a deep SSI increased by 7% for every 10-minute increase in operative time (CI=1.01-1.14, p=0.0335). No significant associations were detected between organ/space infection, wound dehiscence, or DVT and operative time either as continuous or as dichotomized. Prolonged operative times (>90min) are associated with increased rates of superficial SSIs, but not deep SSIs, organ/space infections, wound dehiscence, or DVT. III. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.

PubMed

Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon; Nile, Christopher

2015-08-01

Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

PubMed Central

Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F.; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon

2015-01-01

Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections. PMID:26092919

Chitin Recognition via Chitotriosidase Promotes Pathologic Type-2 Helper T Cell Responses to Cryptococcal Infection

PubMed Central

Wiesner, Darin L.; Specht, Charles A.; Lee, Chrono K.; Smith, Kyle D.; Mukaremera, Liliane; Lee, S. Thera; Lee, Chun G.; Elias, Jack A.; Nielsen, Judith N.; Boulware, David R.; Bohjanen, Paul R.; Jenkins, Marc K.; Levitz, Stuart M.; Nielsen, Kirsten

2015-01-01

Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection. PMID:25764512

Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection.

PubMed

Wiesner, Darin L; Specht, Charles A; Lee, Chrono K; Smith, Kyle D; Mukaremera, Liliane; Lee, S Thera; Lee, Chun G; Elias, Jack A; Nielsen, Judith N; Boulware, David R; Bohjanen, Paul R; Jenkins, Marc K; Levitz, Stuart M; Nielsen, Kirsten

2015-03-01

Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection.

Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells.

PubMed

Dix, Andreas; Czakai, Kristin; Leonhardt, Ines; Schäferhoff, Karin; Bonin, Michael; Guthke, Reinhard; Einsele, Hermann; Kurzai, Oliver; Löffler, Jürgen; Linde, Jörg

2017-01-01

Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused by Candida albicans and Aspergillus fumigatus . The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including the immune response. By analyzing their regulation and impact on target genes, novel therapeutic and diagnostic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infection. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12 h of infection with C. albicans and A. fumigatus as well as treatment with lipopolysaccharides (LPS). We identified 26 microRNAs that are differentially regulated after infection by the fungi or LPS. Three and five of them are specific for fungal infections after 6 and 12 h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as FKBP1B, KLF4 , and SPN , on both RNA and protein level. Our results indicate that these microRNAs fine-tune the expression of immune-related target genes during fungal infection. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during fungal infections and proposes novel microRNAs that could be experimentally verified.

Genotypic Regulation of Aflatoxin Accumulation but Not Aspergillus Fungal Growth upon Post-Harvest Infection of Peanut (Arachis hypogaea L.) Seeds.

PubMed

Korani, Walid Ahmed; Chu, Ye; Holbrook, Corley; Clevenger, Josh; Ozias-Akins, Peggy

2017-07-12

Aflatoxin contamination is a major economic and food safety concern for the peanut industry that largely could be mitigated by genetic resistance. To screen peanut for aflatoxin resistance, ten genotypes were infected with a green fluorescent protein (GFP)-expressing Aspergillus flavus strain. Percentages of fungal infected area and fungal GFP signal intensity were documented by visual ratings every 8 h for 72 h after inoculation. Significant genotypic differences in fungal growth rates were documented by repeated measures and area under the disease progress curve (AUDPC) analyses. SICIA (Seed Infection Coverage and Intensity Analyzer), an image processing software, was developed to digitize fungal GFP signals. Data from SICIA image analysis confirmed visual rating results validating its utility for quantifying fungal growth. Among the tested peanut genotypes, NC 3033 and GT-C20 supported the lowest and highest fungal growth on the surface of peanut seeds, respectively. Although differential fungal growth was observed on the surface of peanut seeds, total fungal growth in the seeds was not significantly different across genotypes based on a fluorometric GFP assay. Significant differences in aflatoxin B levels were detected across peanut genotypes. ICG 1471 had the lowest aflatoxin level whereas Florida-07 had the highest. Two-year aflatoxin tests under simulated late-season drought also showed that ICG 1471 had reduced aflatoxin production under pre-harvest field conditions. These results suggest that all peanut genotypes support A. flavus fungal growth yet differentially influence aflatoxin production.

Genotypic Regulation of Aflatoxin Accumulation but Not Aspergillus Fungal Growth upon Post-Harvest Infection of Peanut (Arachis hypogaea L.) Seeds

PubMed Central

Chu, Ye; Holbrook, Corley; Clevenger, Josh; Ozias-Akins, Peggy

2017-01-01

Aflatoxin contamination is a major economic and food safety concern for the peanut industry that largely could be mitigated by genetic resistance. To screen peanut for aflatoxin resistance, ten genotypes were infected with a green fluorescent protein (GFP)—expressing Aspergillus flavus strain. Percentages of fungal infected area and fungal GFP signal intensity were documented by visual ratings every 8 h for 72 h after inoculation. Significant genotypic differences in fungal growth rates were documented by repeated measures and area under the disease progress curve (AUDPC) analyses. SICIA (Seed Infection Coverage and Intensity Analyzer), an image processing software, was developed to digitize fungal GFP signals. Data from SICIA image analysis confirmed visual rating results validating its utility for quantifying fungal growth. Among the tested peanut genotypes, NC 3033 and GT-C20 supported the lowest and highest fungal growth on the surface of peanut seeds, respectively. Although differential fungal growth was observed on the surface of peanut seeds, total fungal growth in the seeds was not significantly different across genotypes based on a fluorometric GFP assay. Significant differences in aflatoxin B levels were detected across peanut genotypes. ICG 1471 had the lowest aflatoxin level whereas Florida-07 had the highest. Two-year aflatoxin tests under simulated late-season drought also showed that ICG 1471 had reduced aflatoxin production under pre-harvest field conditions. These results suggest that all peanut genotypes support A. flavus fungal growth yet differentially influence aflatoxin production. PMID:28704974

Improvement of fungal disease identification and management: combined health systems and public health approaches.

PubMed

Cole, Donald C; Govender, Nelesh P; Chakrabarti, Arunaloke; Sacarlal, Jahit; Denning, David W

2017-12-01

More than 1·6 million people are estimated to die of fungal diseases each year, and about a billion people have cutaneous fungal infections. Fungal disease diagnosis requires a high level of clinical suspicion and specialised laboratory testing, in addition to culture, histopathology, and imaging expertise. Physicians with varied specialist training might see patients with fungal disease, yet it might remain unrecognised. Antifungal treatment is more complex than treatment for bacterial or most viral infections, and drug interactions are particularly problematic. Health systems linking diagnostic facilities with therapeutic expertise are typically fragmented, with major elements missing in thousands of secondary care and hospital settings globally. In this paper, the last in a Series of eight papers, we describe these limitations and share responses involving a combined health systems and public health framework illustrated through country examples from Mozambique, Kenya, India, and South Africa. We suggest a mainstreaming approach including greater integration of fungal diseases into existing HIV infection, tuberculosis infection, diabetes, chronic respiratory disease, and blindness health programmes; provision of enhanced laboratory capacity to detect fungal diseases with associated surveillance systems; procurement and distribution of low-cost, high-quality antifungal medicines; and concomitant integration of fungal disease into training of the health workforce. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cases of white piedra of the hair on the American continent: a case report and a systematic literature review.

PubMed

Ramírez-Soto, Max Carlos; Andagua-Castro, J; Quispe, Maria Antonieta; Aguilar-Ancori, Elsa G

2018-06-11

White piedra of the hair is a rare superficial fungal infection caused by several Trichosporon spp. 1 It typically manifests as white to light brown hard nodules, firmly attached to frontal, occipital, and parietal scalp hair. 1-9 The incidence of white piedra varies from country to country, and men and women of all ages are affected. 1 In Latin America, children and women appear to be the most affected with white piedra of the hair. 1-9 Given the variability of causative agents and the paucity of literature, very little is known about the geographical distribution of white piedra of the hair in American continent countries to help understand its epidemiology and aid in its diagnosis and treatment. In this report, we describe a case of white piedra of the hair in a Peruvian woman. We also conducted a systematic literature review of all case reports of white piedra on the American continent, with a view to determining the geographical distribution of the condition and identifying Trichosporon spp. commonly associated with this infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.

PubMed

Conti, Heather R; Bruno, Vincent M; Childs, Erin E; Daugherty, Sean; Hunter, Joseph P; Mengesha, Bemnet G; Saevig, Danielle L; Hendricks, Matthew R; Coleman, Bianca M; Brane, Lucas; Solis, Norma; Cruz, J Agustin; Verma, Akash H; Garg, Abhishek V; Hise, Amy G; Richardson, Jonathan P; Naglik, Julian R; Filler, Scott G; Kolls, Jay K; Sinha, Satrajit; Gaffen, Sarah L

2016-11-09

Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17ra ΔK13 ). Following oral Candida infection, Il17ra ΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra -/- mice. Susceptibility in Il17ra ΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3 -/- mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic penetrating keratoplasty in severe fungal keratitis using cryopreserved donor corneas

PubMed Central

Yao, Y-F; Zhang, Y-M; Zhou, P; Zhang, B; Qiu, W-Y; Tseng, S C G

2003-01-01

Aims: To investigate whether cryopreserved donor cornea could be used for therapeutic penetrating keratoplasty (PKP) to eradicate the infection, obviate complications, and preserve anatomical integrity in severe fungal keratitis. Methods: In this retrospective, consecutive case series, 45 eyes of 45 patients with severe fungal keratitis, which exhibited anterior chamber collapse, corneal perforation, and/or large suppurative corneal infiltrate, received therapeutic PKP after removal of the infected corneal tissue, irrigation of the anterior chamber by 0.2% fluconazole solution, iris dissection of fibrinoid membrane, and iridectomy and therapeutic PKP using corneas cryopreserved at −20°C. Results: Among 45 eyes, 39 eyes (86.7%) were successfully eradicated the fungal infection without recurrence and maintained their anatomical integrity without any complication. Four of 45 eyes (8.9%) showed postoperative rise of intraocular pressure, of which three were controlled with subsequent antiglaucoma surgeries, whereas one eye needed additional antiglaucoma medications. Two of 45 eyes (4.4%) were enucleated because of uncontrollable fungal infection and secondary retinal detachment, respectively. 23 eyes received subsequent optical PKP and, among them, 21 maintained clear corneal grafts and two suffered from graft failure due to allograft rejections. Conclusion: Cryopreserved donor corneas are effective substitutes in therapeutic PKP to control severe fungal corneal infection and preserve the global integrity, and may offer additional advantages over conventional PKP in reducing allograft rejection, eradicating fungal infection during the postoperative period, and improving the success of optical PKP for visual rehabilitation. PMID:12714387

Sphingolipids as targets for treatment of fungal infections

PubMed Central

Rollin-Pinheiro, Rodrigo; Singh, Ashutosh; Barreto-Bergter, Eliana; Del Poeta, Maurizio

2016-01-01

Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids. PMID:27502288

Dectin-1 is required for β-glucan recognition and control of fungal infection

PubMed Central

Taylor, Philip R; Tsoni, S Vicky; Willment, Janet A; Dennehy, Kevin M; Rosas, Marcela; Findon, Helen; Haynes, Ken; Steele, Chad; Botto, Marina; Gordon, Siamon; Brown, Gordon D

2007-01-01

β-Glucan is one of the most abundant polysaccharides in fungal pathogens, yet its importance in antifungal immunity is unclear. Here we show that deficiency of dectin-1, the myeloid receptor for β-glucan, rendered mice susceptible to infection with Candida albicans. Dectin-1-deficient leukocytes demonstrated significantly impaired responses to fungi even in the presence of opsonins. Impaired leukocyte responses were manifested in vivo by reduced inflammatory cell recruitment after fungal infection, resulting in substantially increased fungal burdens and enhanced fungal dissemination. Our results establish a fundamental function for β-glucan recognition by dectin-1 in antifungal immunity and demonstrate a signaling non–Toll-like pattern-recognition receptor required for the induction of protective immune responses. PMID:17159984

Dermatophytosis in military in the central-west region of Brazil: literature review.

PubMed

Leite, Diniz Pereira; Amadio, Janaina Vasconcellos R de Souza; Simões, Sara de Almeida Alves; de Araújo, Sebastião Martins; da Silva, Nicolina Maria Rodrigues; Anzai, Mariana Cazelli; Hahn, Rosane Christine

2014-02-01

Dermatophytes represent a group of keratinophilic fungi capable of invading the superficial layer of the skin, hair, and nails of humans and animals. There is a high prevalence of dermatomycosis in tropical regions, and military personnel are susceptible to this kind of infection due to the type of occupational activities. This study was to investigate dermatophytosis in military, in addition to predisposing factors to such infections. The direct examination of the 221 samples obtained was conducted by preparing fresh slides, clarified with KOH. The clinical materials were seeded in duplicate in SDA and in Mycosel agar medium. The identification of the etiologic agents was performed according to the Riddell technique. 99/221 (44.8 %) of the dermatophyte infection agents distributed in the three taxonomic genera that cause Tinea were recovered. The Trichophyton genus was the most representative and T. rubrum species 33 (33.3 %), the most prevalent. The other species found were as follows: T. tonsurans 13 (13.1 %), T. verrucosum 11 (11.1 %), T. interdigitale 9 (9.1 %), and T. mentagrophytes 6 (6.1 %). Among the most affected anatomical sites were skin 83 (83.8 %) and nails 17 (17.2 %). Dermatophyte infections are common disorders in tropical countries. These infections lead to a variety of clinical manifestations. This study reports the incidence of dermatophytosis in the military personnel in the Central-West Region of Brazil. The occupational activities of the military individuals, in addition to the hot and humid climate of the region, can predispose them to infection by these fungal entities.

Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo

Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infectedmore » by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.« less

Itraconazole

MedlinePlus

Itraconazole capsules are used to treat fungal infections in the lungs that can spread throughout the body. Itraconazole capsules are also used to treat fungal infections of the fingernails. Itraconazole tablets ...

Candida-streptococcal mucosal biofilms display distinct structural and virulence characteristics depending on growth conditions and hyphal morphotypes.

PubMed

Bertolini, M M; Xu, H; Sobue, T; Nobile, C J; Del Bel Cury, A A; Dongari-Bagtzoglou, A

2015-08-01

Candida albicans and streptococci of the mitis group form communities in multiple oral sites, where moisture and nutrient availability can change spatially or temporally. This study evaluated structural and virulence characteristics of Candida-streptococcal biofilms formed on moist or semidry mucosal surfaces, and tested the effects of nutrient availability and hyphal morphotype on dual-species biofilms. Three-dimensional models of the oral mucosa formed by immortalized keratinocytes on a fibroblast-embedded collagenous matrix were used. Infections were carried out using Streptococcus oralis strain 34, in combination with a C. albicans wild-type strain, or pseudohyphal-forming mutant strains. Increased moisture promoted a homogeneous surface biofilm by C. albicans. Dual biofilms had a stratified structure, with streptococci growing in close contact with the mucosa and fungi growing on the bacterial surface. Under semidry conditions, Candida formed localized foci of dense growth, which promoted focal growth of streptococci in mixed biofilms. Candida biofilm biovolume was greater under moist conditions, albeit with minimal tissue invasion, compared with semidry conditions. Supplementing the infection medium with nutrients under semidry conditions intensified growth, biofilm biovolume and tissue invasion/damage, without changing biofilm structure. Under these conditions, the pseudohyphal mutants and S. oralis formed defective superficial biofilms, with most bacteria in contact with the epithelial surface, below a pseudohyphal mass, resembling biofilms growing in a moist environment. The presence of S. oralis promoted fungal invasion and tissue damage under all conditions. We conclude that moisture, nutrient availability, hyphal morphotype and the presence of commensal bacteria influence the architecture and virulence characteristics of mucosal fungal biofilms. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of snake fungal disease due to Ophidiomyces ophiodiicola in Virginia, USA

USGS Publications Warehouse

Guthrie, Amanda L.; Knowles, Susan N.; Ballmann, Anne; Lorch, Jeffrey M.

2015-01-01

Snake fungal disease (SFD) is an emerging disease of wildlife believed to be caused by Ophidiomyces ophiodiicola. Although geographic and host ranges have yet to be determined, this disease is characterized by crusty scales, superficial pustules, and subcutaneous nodules, with subsequent morbidity and mortality in some snake species. To confirm the presence of SFD and O. ophiodiicola in snakes of eastern Virginia, USA, we clinically examined 30 free-ranging snakes on public lands from April to October 2014. Skin biopsy samples were collected from nine snakes that had gross lesions suggestive of SFD; seven of these biopsies were suitable for histologic interpretation, and eight were suitable for culture and PCR detection of O. ophiodiicola. Seven snakes had histologic features consistent with SFD and were positive for O. ophiodiicola by PCR or fungal culture.

Detection of Snake Fungal Disease Due to Ophidiomyces ophiodiicola in Virginia, USA.

PubMed

Guthrie, Amanda L; Knowles, Susan; Ballmann, Anne E; Lorch, Jeffrey M

2016-01-01

Snake fungal disease (SFD) is an emerging disease of wildlife believed to be caused by Ophidiomyces ophiodiicola. Although geographic and host ranges have yet to be determined, this disease is characterized by crusty scales, superficial pustules, and subcutaneous nodules, with subsequent morbidity and mortality in some snake species. To confirm the presence of SFD and O. ophiodiicola in snakes of eastern Virginia, US, we clinically examined 30 free-ranging snakes on public lands from April to October 2014. Skin biopsy samples were collected from nine snakes that had gross lesions suggestive of SFD; seven of these biopsies were suitable for histologic interpretation, and eight were suitable for culture and PCR detection of O. ophiodiicola. Seven snakes had histologic features consistent with SFD and eight were positive for O. ophiodiicola by PCR or fungal culture.

Estimated burden of fungal infections in Germany.

PubMed

Ruhnke, Markus; Groll, Andreas H; Mayser, Peter; Ullmann, Andrew J; Mendling, Werner; Hof, Herbert; Denning, David W

2015-10-01

In the late 1980's, the incidence of invasive fungal diseases (IFDs) in Germany was estimated with 36.000 IFDs per year. The current number of fungal infections (FI) occurring each year in Germany is still not known. In the actual analysis, data on incidence of fungal infections in various patients groups at risk for FI were calculated and mostly estimated from various (mostly national) resources. According to the very heterogenous data resources robust data or statistics could not be obtained but preliminary estimations could be made and compared with data from other areas in the world using a deterministic model that has consistently been applied in many countries by the LIFE program ( www.LIFE-worldwide.org). In 2012, of the 80.52 million population (adults 64.47 million; 41.14 million female, 39.38 million male), 20% are children (0-14 years) and 16% of population are ≥65 years old. Using local data and literature estimates of the incidence or prevalence of fungal infections, about 9.6 million (12%) people in Germany suffer from a fungal infection each year. These figures are dominated (95%) by fungal skin disease and recurrent vulvo-vaginal candidosis. In general, considerable uncertainty surrounds the total numbers because IFDs do not belong to the list of reportable infectious diseases in Germany and most patients were not hospitalised because of the IFD but a distinct underlying disease. © 2015 Blackwell Verlag GmbH.

The role of the cell wall in fungal pathogenesis

PubMed Central

Arana, David M.; Prieto, Daniel; Román, Elvira; Nombela, César; Alonso‐Monge, Rebeca; Pla, Jesús

2009-01-01

Summary Fungal infections are a serious health problem. In recent years, basic research is focusing on the identification of fungal virulence factors as promising targets for the development of novel antifungals. The wall, as the most external cellular component, plays a crucial role in the interaction with host cells mediating processes such as adhesion or phagocytosis that are essential during infection. Specific components of the cell wall (called PAMPs) interact with specific receptors in the immune cell (called PRRs), triggering responses whose molecular mechanisms are being elucidated. We review here the main structural carbohydrate components of the fungal wall (glucan, mannan and chitin), how their biogenesis takes place in fungi and the specific receptors that they interact with. Different model fungal pathogens are chosen to illustrate the functional consequences of this interaction. Finally, the identification of the key components will have important consequences in the future and will allow better approaches to treat fungal infections. PMID:21261926

Bedside ultrasound of the soft tissue of the face: a case of early Ludwig's angina.

PubMed

Gaspari, Romolo J

2006-10-01

A case is reported of a 38-year-old man presenting with early Ludwig's angina. It is difficult to differentiate superficial from deep infections of the face and neck by physical examination alone. The diagnosis of this condition with bedside soft tissue ultrasound of the face is described. Ludwig's angina is an uncommon infection of the deep tissues of the face and neck that usually evolves from more superficial infections such as dental abscesses.

A pathogenesis assay using Saccharomyces cerevisiae and Caenorhabditis elegans reveals novel roles for yeast AP-1, Yap1, and host dual oxidase BLI-3 in fungal pathogenesis.

PubMed

Jain, Charu; Yun, Meijiang; Politz, Samuel M; Rao, Reeta Prusty

2009-08-01

Treatment of systemic fungal infections is difficult because of the limited number of antimycotic drugs available. Thus, there is an immediate need for simple and innovative systems to assay the contribution of individual genes to fungal pathogenesis. We have developed a pathogenesis assay using Caenorhabditis elegans, an established model host, with Saccharomyces cerevisiae as the invading fungus. We have found that yeast infects nematodes, causing disease and death. Our data indicate that the host produces reactive oxygen species (ROS) in response to fungal infection. Yeast mutants sod1Delta and yap1Delta, which cannot withstand ROS, fail to cause disease, except in bli-3 worms, which carry a mutation in a dual oxidase gene. Chemical inhibition of the NADPH oxidase activity abolishes ROS production in worms exposed to yeast. This pathogenesis assay is useful for conducting systematic, whole-genome screens to identify fungal virulence factors as alternative targets for drug development and exploration of host responses to fungal infections.

Pseudogymnoascus destructans transcriptome changes during white-nose syndrome infections

PubMed Central

Reeder, Sophia M.; Palmer, Jonathan M.; Prokkola, Jenni M.; Lilley, Thomas M.; Reeder, DeeAnn M.

2017-01-01

ABSTRACT White nose syndrome (WNS) is caused by the psychrophilic fungus Pseudogymnoascus destructans that can grow in the environment saprotrophically or parasitically by infecting hibernating bats. Infections are pathological in many species of North American bats, disrupting hibernation and causing mortality. To determine what fungal pathways are involved in infection of living tissue, we examined fungal gene expression using RNA-Seq. We compared P. destructans gene expression when grown in culture to that during infection of a North American bat species, Myotis lucifugus, that shows high WNS mortality. Cultured P. destructans was grown at 10 to 14 C and P. destructans growing in vivo was presumably exposed to temperatures ranging from 4 to 8 C during torpor and up to 37 C during periodic arousals. We found that when P. destructans is causing WNS, the most significant differentially expressed genes were involved in heat shock responses, cell wall remodeling, and micronutrient acquisition. These results indicate that this fungal pathogen responds to host-pathogen interactions by regulating gene expression in ways that may contribute to evasion of host responses. Alterations in fungal cell wall structures could allow P. destructans to avoid detection by host pattern recognition receptors and antibody responses. This study has also identified several fungal pathways upregulated during WNS infection that may be candidates for mitigating infection pathology. By identifying host-specific pathogen responses, these observations have important implications for host-pathogen evolutionary relationships in WNS and other fungal diseases. PMID:28614673

Pseudogymnoascus destructans transcriptome changes during white-nose syndrome infections.

PubMed

Reeder, Sophia M; Palmer, Jonathan M; Prokkola, Jenni M; Lilley, Thomas M; Reeder, DeeAnn M; Field, Kenneth A

2017-11-17

White nose syndrome (WNS) is caused by the psychrophilic fungus Pseudogymnoascus destructans that can grow in the environment saprotrophically or parasitically by infecting hibernating bats. Infections are pathological in many species of North American bats, disrupting hibernation and causing mortality. To determine what fungal pathways are involved in infection of living tissue, we examined fungal gene expression using RNA-Seq. We compared P. destructans gene expression when grown in culture to that during infection of a North American bat species, Myotis lucifugus, that shows high WNS mortality. Cultured P. destructans was grown at 10 to 14 C and P. destructans growing in vivo was presumably exposed to temperatures ranging from 4 to 8 C during torpor and up to 37 C during periodic arousals. We found that when P. destructans is causing WNS, the most significant differentially expressed genes were involved in heat shock responses, cell wall remodeling, and micronutrient acquisition. These results indicate that this fungal pathogen responds to host-pathogen interactions by regulating gene expression in ways that may contribute to evasion of host responses. Alterations in fungal cell wall structures could allow P. destructans to avoid detection by host pattern recognition receptors and antibody responses. This study has also identified several fungal pathways upregulated during WNS infection that may be candidates for mitigating infection pathology. By identifying host-specific pathogen responses, these observations have important implications for host-pathogen evolutionary relationships in WNS and other fungal diseases.

Use of an Artificial Neural Network to Construct a Model of Predicting Deep Fungal Infection in Lung Cancer Patients.

PubMed

Chen, Jian; Chen, Jie; Ding, Hong-Yan; Pan, Qin-Shi; Hong, Wan-Dong; Xu, Gang; Yu, Fang-You; Wang, Yu-Min

2015-01-01

The statistical methods to analyze and predict the related dangerous factors of deep fungal infection in lung cancer patients were several, such as logic regression analysis, meta-analysis, multivariate Cox proportional hazards model analysis, retrospective analysis, and so on, but the results are inconsistent. A total of 696 patients with lung cancer were enrolled. The factors were compared employing Student's t-test or the Mann-Whitney test or the Chi-square test and variables that were significantly related to the presence of deep fungal infection selected as candidates for input into the final artificial neural network analysis (ANN) model. The receiver operating characteristic (ROC) and area under curve (AUC) were used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of deep fungal infection from lung cancer in this entire study population was 32.04%(223/696), deep fungal infections occur in sputum specimens 44.05% (200/454). The ratio of candida albicans was 86.99% (194/223) in the total fungi. It was demonstrated that older (≥65 years), use of antibiotics, low serum albumin concentrations (≤37.18 g /L), radiotherapy, surgery, low hemoglobin hyperlipidemia (≤93.67 g /L), long time of hospitalization (≥14 days) were apt to deep fungal infection and the ANN model consisted of the seven factors. The AUC of ANN model (0.829±0.019) was higher than that of LR model (0.756±0.021). The artificial neural network model with variables consisting of age, use of antibiotics, serum albumin concentrations, received radiotherapy, received surgery, hemoglobin, time of hospitalization should be useful for predicting the deep fungal infection in lung cancer.

Prevalence and factors predictive of intraocular fungal infection in patients with fungemia at an academic urban tertiary care center.

PubMed

Geraymovych, Elena; Conduff, Joseph H; Braich, Puneet S; Leffler, Christopher T; Brar, Vikram S

2015-01-01

To report the prevalence and to identify factors predictive of intraocular infection in patients with fungemia receiving prophylactic antifungal therapy. A retrospective review of patients who received prophylactic antifungal therapy and a dilated fundus examination at an academic urban tertiary care center from 2000 to 2007. Basic demographic information, fungal species grown, antifungal agent(s) used, number of positive blood culture specimens, visual acuity, visual symptoms, and known risks of disseminated candidiasis were noted. Logistic regression analysis was used to determine the factors significantly associated with intraocular fungal infection. A total of 132 patients with positive fungemia culture were requested to have ophthalmology consults. The prevalence of ocular infection was 6.9% (N=9). All nine patients were infected with Candida species. Undergoing gastrointestinal (GI) surgery within the prior 6 months was significantly related to developing intraocular infection, with an odds ratio of 18.5 (95% confidence interval, 15.1-24.3; P=0.002). Having ≥3 positive fungal blood cultures was also a significant risk factor, with an odds ratio of 2.6 (95% confidence interval, 1.8-3.7; P=0.03). Among 40 patients having GI surgery, eight (20.0%) had intraocular fungal disease, compared with one of 92 patients (1.1%) not having GI surgery. Among 125 patients with a negative baseline examination result, two of 32 patients (6.3%), who had recent GI surgery, subsequently developed fungal ocular disease, compared with 0 of 93 patients (0%), who did not have recent GI surgery. Recent GI surgery and higher numbers of positive fungal blood culture specimens may be predictive of candida ocular infections. Normal baseline fundoscopy examination results in patients with such risks may require repeat evaluations to detect delayed manifestations.

A randomized, multicenter, double-blind, vehicle-controlled study evaluating the efficacy and safety of luliconazole cream 1% once daily for 7 days in patients aged ≥ 12 years with tinea cruris.

PubMed

Jones, Terry M; Jarratt, Michael T; Mendez-Moguel, Ines; Paz, Nelly; Grekin, Steven K; Cognata Smith, Christina; Kaur, Mandeep

2014-01-01

Tinea cruris, a pruritic superficial fungal infection of the groin, is the second most common clinical presentation for dermatophytosis. This phase 3 study evaluated the safety and efficacy of topical luliconazole cream 1% in patients with tinea cruris. 483 patients were enrolled and 256 male and female patients aged ≥12 years with clinically evident tinea cruris and eligible for modified intent-to-treat analysis were randomized 2:1 to receive luliconazole cream 1% (n=165) or vehicle (n=91) once daily for 7 days. Efficacy was evaluated at baseline and at days 7, 14, 21, and 28 based on mycology (potassium hydroxide, fungal culture) and clinical signs (erythema, scaling, pruritus). The primary outcome was complete clearance at day 28 (21 days posttreatment). Safety evaluations included adverse events and laboratory assessments. Complete clearance was obtained in 21.2% (35/165) of patients treated with luliconazole cream 1% compared with 4.4% (4/91) treated with vehicle (P<0.001). The safety profile of luliconazole cream 1% was similar to vehicle. The study was conducted under controlled conditions in a relatively small population. Luliconazole cream 1% applied once daily for 7 days is more effective than vehicle and well tolerated in patients with tinea cruris.

Estimated burden of fungal infections in Kenya.

PubMed

Guto, John Abuga; Bii, Christine C; Denning, David W

2016-08-31

Kenya is a developing country with a high rate of tuberculosis (TB) and a moderate HIV infection burden. No estimate of the burden of fungal diseases in Kenya is published. We used specific populations at risk and fungal infection frequencies from the literature to estimate national incidence or prevalence of serious fungal infections. Used sources were: 2010 WHO TB statistics, Kenya Acquired Immunodeficiency Syndrome (AIDS) Epidemic Update 2012, Kenya Facts and figures 2012, Kenya Demographic and Health Survey 2008-2009. Of Kenya's population of ~40 million, 43% are under 15 years old and approximately 594,660 Kenyan women get >4 episodes Candida vulvovaginitis annually (2,988/100,000). The HIV/AIDS population at risk of opportunistic infections (OI) is 480,000 and the OI estimates include 306,000 patients with oral thrush (768/100,000), 114,000 with oesophageal candidiasis (286/100,000), 11,900 with cryptococcal meningitis (29/100,000) and 17,000 patients with Pneumocystis pneumonia (42/100,000). Chronic pulmonary aspergillosis following TB has a prevalence of 10,848 cases (32/100,000). The adult asthma prevalence is 3.1% and assuming 2.5% have allergic bronchopulmonary aspergillosis then 17,696 (44/100,000) are affected.  Invasive aspergillosis, candidaemia and Candida peritonitis are probably uncommon. Tinea capitis infects 9.6% of children in Kenya, while fungal keratitis and otomycoses are difficult to estimate. At any one time, about 7% of the Kenyan population suffers from a significant fungal infection, with recurrent vaginitis and tinea capitis accounting for 82% of the infections. These estimates require further epidemiological studies for validation.

Sulfur fertilization and fungal infections affect the exchange of H(2)S and COS from agricultural crops.

PubMed

Bloem, Elke; Haneklaus, Silvia; Kesselmeier, Jürgen; Schnug, Ewald

2012-08-08

The emission of gaseous sulfur (S) compounds by plants is related to several factors, such as the plant S status or fungal infection. Hydrogen sulfide (H(2)S) is either released or taken up by the plant depending on the ambient air concentration and the plant demand for S. On the contrary, carbonyl sulfide (COS) is normally taken up by plants. In a greenhouse experiment, the dependence of H(2)S and COS exchange with ambient air on the S status of oilseed rape (Brassica napus L.) and on fungal infection with Sclerotinia sclerotiorum was investigated. Thiol contents were determined to understand their influence on the exchange of gaseous S compounds. The experiment revealed that H(2)S emissions were closely related to pathogen infections as well as to S nutrition. S fertilization caused a change from H(2)S consumption by S-deficient oilseed rape plants to a H(2)S release of 41 pg g(-1) (dw) min(-1) after the addition of 250 mg of S per pot. Fungal infection caused an even stronger increase of H(2)S emissions with a maximum of 1842 pg g(-1) (dw) min(-1) 2 days after infection. Healthy oilseed rape plants acted as a sink for COS. Fungal infection caused a shift from COS uptake to COS releases. The release of S-containing gases thus seems to be part of the response to fungal infection. The roles the S-containing gases may play in this response are discussed.

May one-stage exchange for Candida albicans peri-prosthetic infection be successful?

PubMed

Jenny, J-Y; Goukodadja, O; Boeri, C; Gaudias, J

2016-02-01

Fungal infection of a total joint arthroplasty has a low incidence but is generally considered as more difficult to cure than bacterial infection. As for bacterial infection, two-stage exchange is considered as the gold standard of treatment. We report two cases of one-stage total joint exchange for fungal peri-prosthetic infection with Candida albicans, where the responsible pathogens was only identified on intraoperative samples. This situation can be considered as a one-stage exchange for fungal peri-prosthetic infection without preoperative identification of the responsible organism, which is considered as having a poor prognosis. Both cases were free of infection after two years. One-stage revision has several potential advantages over two-stage revision, including shorter hospital stay and rehabilitation, no interim period with significant functional impairment, shorter antibiotic treatment, better functional outcome and probably lower costs. We suggest that one-stage revision for C. albicans peri-prosthetic infection may be successful even without preoperative fungal identification. Level IV-Historical cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Infection Unit Density as an Index of Infection Potential of Arbuscular Mycorrhizal Fungi.

PubMed

Ohtomo, Ryo; Kobae, Yoshihiro; Morimoto, Sho; Oka, Norikuni

2018-03-29

The effective use of arbuscular mycorrhizal (AM) fungal function to promote host plant phosphate uptake in agricultural practice requires the accurate quantitative evaluation of AM fungal infection potential in field soil or AM fungal inoculation material. The number of infection units (IUs), intraradical fungal structures derived from single root entries formed after a short cultivation period, may reflect the number of propagules in soil when pot soil is completely permeated by the host root. However, the original IU method, in which all AM propagules in a pot are counted, requires the fine tuning of plant growing conditions and is considered to be laborious. The objective of the present study was to test whether IU density, not the total count of IU, but the number of IUs per unit root length, reflects the density of AM fungal propagules in soil. IU density assessed after 12 d of host plant cultivation and 3,3'-diaminobenzidine (DAB) staining showed a stronger linear correlation with propagule density than the mean infection percentage (MIP). In addition, IU density was affected less by the host plant species than MIP. We suggest that IU density provides a more rapid and reliable quantitation of the propagule density of AM fungi than MIP or the original IU method. Thus, IU density may be a more robust index of AM fungal infection potential for research and practical applications.

Analysis of Whitefly Transcriptional Responses to Beauveria bassiana Infection Reveals New Insights into Insect-Fungus Interactions

PubMed Central

Zhang, Shan; Li, Fang-Fang; Feng, Ming-Guang; Wang, Xiao-Wei; Liu, Shu-Sheng

2013-01-01

Background The fungal pathogen, Beauveria bassiana, is an efficient biocontrol agent against a variety of agricultural pests. A thorough understanding of the basic principles of insect-fungus interactions may enable the genetic modification of Beauveria bassiana to enhance its virulence. However, the molecular mechanism of insect response to Beauveria bassiana infection is poorly understood, let alone the identification of fungal virulent factors involved in pathogenesis. Methodology/Principal Findings Here, next generation sequencing technology was applied to examine the expression of whitefly (Bemisia tabaci) genes in response to the infection of Beauveria bassiana. Results showed that, compared to control, 654 and 1,681genes were differentially expressed at 48 hours and 72 hours post-infected whiteflies, respectively. Functional and enrichment analyses indicated that the DNA damage stimulus response and drug metabolism were important anti-fungi strategies of the whitefly. Mitogen-activated protein kinase (MAPK) pathway was also likely involved in the whitefly defense responses. Furthermore, the notable suppression of general metabolism and ion transport genes observed in 72 hours post-infected B. tabaci might be manipulated by fungal secreted effectors. By mapping the sequencing tags to B. bassiana genome, we also identified a number of differentially expressed fungal genes between the early and late infection stages. These genes are generally associated with fungal cell wall synthesis and energy metabolism. The expression of fungal cell wall protein genes might play an important role in fungal pathogenesis and the dramatically up-regulated enzymes of carbon metabolism indicate the increasing usage of energy during the fungal infection. Conclusions/Significance To our knowledge, this is the first report on the molecular mechanism of fungus-whitefly interactions. Our results provide a road map for future investigations on insect-pathogen interactions and genetically modifying the fungus to enhance its efficiency in whitefly control. PMID:23861870

Non-destructive techniques for the detection of fungal infection in cereal grains.

PubMed

Orina, Irene; Manley, Marena; Williams, Paul J

2017-10-01

Infection of cereal grains by fungi is a serious problem worldwide. Depending on the environmental conditions, cereal grains may be colonised by different species of fungi. These fungi cause reduction in yield, quality and nutritional value of the grain; and of major concern is their production of mycotoxins which are harmful to both humans and animals. Early detection of fungal contamination is an essential control measure for ensuring storage longevity and food safety. Conventional methods for detection of fungal infection, such as culture and colony techniques or immunological methods are either slow, labour intensive or difficult to automate. In recent years, there has been an increasing need to develop simple, rapid, non-destructive methods for early detection of fungal infection and mycotoxins contamination in cereal grains. Methods such as near infrared (NIR) spectroscopy, NIR hyperspectral imaging, and electronic nose were evaluated for these purposes. This paper reviews the different non-destructive techniques that have been considered thus far for detection of fungal infection and mycotoxins in cereal grains, including their principles, application and limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Enhanced microscopic diagnosis of oesophageal candidiasis through additional cytospin analysis of the fixative of oesophageal biopsies].

PubMed

Schröder, Sören; Günther, Thomas

2018-05-09

To confirm or to refute the diagnosis of candida oesophagitis as the most common infectious disease of the oesophagus is a standard diagnostic procedure in histopathology. The fungal hyphae colonise mainly the superficial layers of the oesophageal squamous mucosa. Tangentially cut sections of oesophageal biopsies in the paraffin block might lead to a false negative result concerning mycotic infection. The aim of this study was to investigate whether cytospin analysis of the formalin fixative in which the biopsies were stored and transported would be a tool to close the diagnostic gap.Oesophageal biopsies from 150 consecutive patients with the clinical diagnosis or question "candida" or "candida oesophagitis" have been investigated. The biopsies were routinely processed and stained with haematoxylin and eosin and periodic acid-Schiff reaction. In parallel, the fixative fluid, usually disposed of after use, was processed by using a cytospin centrifuge and prepared for cytological proof of fungal hyphae. The cytology slides were also stained with periodic acid-Schiff reaction. In this blind study, the pathologist investigating the results of one procedure was unaware of the results of the second procedure.Out of 89 positive cytology cases, 64 cases (71,9 %) also showed a positive histology result. In the remaining 25 cases (28,1 %), fungal hyphae were seen only after re-evaluation of the original histology slides (n = 6) or in further serial sections using the complete tissue in the block (n = 5). In 14 cases, no hyphae could be detected histologically. Only in one of the 61 cytospin-negative cases was candida seen in histology.Our results show that diagnosing oesophageal candidiasis can be improved by more than one quarter using the formalin fixative for cytospin cytology. © Georg Thieme Verlag KG Stuttgart · New York.

Long-distance endosome trafficking drives fungal effector production during plant infection

PubMed Central

Bielska, Ewa; Higuchi, Yujiro; Schuster, Martin; Steinberg, Natascha; Kilaru, Sreedhar; Talbot, Nicholas J.; Steinberg, Gero

2014-01-01

To cause plant disease, pathogenic fungi can secrete effector proteins into plant cells to suppress plant immunity and facilitate fungal infection. Most fungal pathogens infect plants using very long strand-like cells, called hyphae, that secrete effectors from their tips into host tissue. How fungi undergo long-distance cell signalling to regulate effector production during infection is not known. Here we show that long-distance retrograde motility of early endosomes (EEs) is necessary to trigger transcription of effector-encoding genes during plant infection by the pathogenic fungus Ustilago maydis. We demonstrate that motor-dependent retrograde EE motility is necessary for regulation of effector production and secretion during host cell invasion. We further show that retrograde signalling involves the mitogen-activated kinase Crk1 that travels on EEs and participates in control of effector production. Fungal pathogens therefore undergo long-range signalling to orchestrate host invasion. PMID:25283249

Long-distance endosome trafficking drives fungal effector production during plant infection.

PubMed

Bielska, Ewa; Higuchi, Yujiro; Schuster, Martin; Steinberg, Natascha; Kilaru, Sreedhar; Talbot, Nicholas J; Steinberg, Gero

2014-10-06

To cause plant disease, pathogenic fungi can secrete effector proteins into plant cells to suppress plant immunity and facilitate fungal infection. Most fungal pathogens infect plants using very long strand-like cells, called hyphae, that secrete effectors from their tips into host tissue. How fungi undergo long-distance cell signalling to regulate effector production during infection is not known. Here we show that long-distance retrograde motility of early endosomes (EEs) is necessary to trigger transcription of effector-encoding genes during plant infection by the pathogenic fungus Ustilago maydis. We demonstrate that motor-dependent retrograde EE motility is necessary for regulation of effector production and secretion during host cell invasion. We further show that retrograde signalling involves the mitogen-activated kinase Crk1 that travels on EEs and participates in control of effector production. Fungal pathogens therefore undergo long-range signalling to orchestrate host invasion.

Detection of fungal DNA in human body fluids and tissues during a multistate outbreak of fungal meningitis and other infections.

PubMed

Gade, Lalitha; Scheel, Christina M; Pham, Cau D; Lindsley, Mark D; Iqbal, Naureen; Cleveland, Angela Ahlquist; Whitney, Anne M; Lockhart, Shawn R; Brandt, Mary E; Litvintseva, Anastasia P

2013-05-01

Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak.

Fusarium musae as cause of superficial and deep-seated human infections.

PubMed

Esposto, M C; Prigitano, A; Tortorano, A M

2016-12-01

BLAST analysis in GenBank of 60 Fusarium verticillioides clinical isolates using the sequence of translation elongation factor 1-alpha allowed the identification of four F. musae confirming that this species is not a rare etiology of superficial and deep infections and that its habitat is not restricted to banana fruits. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Burden of serious fungal infections in the Czech Republic.

PubMed

Chrdle, Aleš; Mallátová, Nad'a; Vašáková, Martina; Haber, Jan; Denning, David W

2015-10-01

We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care. © 2015 Blackwell Verlag GmbH.

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation.

PubMed

Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

2018-01-01

Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA's phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans . We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis. PPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation.

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

PubMed Central

Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

2018-01-01

Background Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. Results A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans. We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis. Conclusion PPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation. PMID:29692614

Prophylactic Saccharomyces boulardii versus nystatin for the prevention of fungal colonization and invasive fungal infection in premature infants.

PubMed

Demirel, Gamze; Celik, Istemi Han; Erdeve, Omer; Saygan, Sibel; Dilmen, Ugur; Canpolat, Fuat Emre

2013-10-01

This study aims to compare the efficacy of orally administered Saccharomyces boulardii versus nystatin in prevention of fungal colonization and invasive fungal infections in very low birth weight infants. A prospective, randomized comparative study was conducted in preterm infants with a gestational age of ≤ 32 weeks and birth weight of ≤ 1,500 g. They were randomized into two groups, to receive S. boulardii or nystatin. Skin and stool cultures were performed for colonization and blood cultures for invasive infections, weekly. A total of 181 infants were enrolled (S. boulardii group, n = 91; nystatin group, n = 90). Fungal colonization of the skin (15.4 vs 18.9 %, p = 0.532) and the stool (32.2 vs 27 %, p = 0.441) were not different between the probiotic and nystatin groups. Two patients had Candida-positive blood culture in the nystatin group whereas none in the probiotic group. Feeding intolerance, clinical sepsis, and number of sepsis attacks were significantly lower in the probiotics group than in the nystatin group. Prophylactic S. boulardii supplementation is as effective as nystatin in reducing fungal colonization and invasive fungal infection, more effective in reducing the incidence of clinical sepsis and number of sepsis attacks and has favorable effect on feeding intolerance.

Highly Discriminatory Variable-Number Tandem-Repeat Markers for Genotyping of Trichophyton interdigitale Strains

PubMed Central

Drira, Ines; Hadrich, Ines; Neji, Sourour; Mahfouth, Nedia; Trabelsi, Houaida; Sellami, Hayet; Makni, Fattouma

2014-01-01

Trichophyton interdigitale is the second most frequent cause of superficial fungal infections of various parts of the human body. Studying the population structure and genotype differentiation of T. interdigitale strains may lead to significant improvements in clinical practice. The present study aimed to develop and select suitable variable-number tandem-repeat (VNTR) markers for 92 clinical strains of T. interdigitale. On the basis of an analysis of four VNTR markers, four to eight distinct alleles were detected for each marker. The marker with the highest discriminatory power had eight alleles and a D value of 0.802. The combination of all four markers yielded a D value of 0.969 with 29 distinct multilocus genotypes. VNTR typing revealed the genetic diversity of the strains, identifying three populations according to their colonization sites. A correlation between phenotypic characteristics and multilocus genotypes was observed. Seven patients harbored T. interdigitale strains with different genotypes. Typing of clinical T. interdigitale samples by VNTR markers displayed excellent discriminatory power and 100% reproducibility. PMID:24989614

Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood.

PubMed

Prauße, Maria T E; Lehnert, Teresa; Timme, Sandra; Hünniger, Kerstin; Leonhardt, Ines; Kurzai, Oliver; Figge, Marc Thilo

2018-01-01

Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata . However, differences between the immune-evasion models could be observed for the infection outcome under neutropenic conditions with respect to the distribution of fungal cells across the immune cells. Based on these predictions, we suggested specific experimental studies that might allow for the validation or rejection of the proposed immune-evasion mechanism.

Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood

PubMed Central

Prauße, Maria T. E.; Lehnert, Teresa; Timme, Sandra; Hünniger, Kerstin; Leonhardt, Ines; Kurzai, Oliver; Figge, Marc Thilo

2018-01-01

Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata. However, differences between the immune-evasion models could be observed for the infection outcome under neutropenic conditions with respect to the distribution of fungal cells across the immune cells. Based on these predictions, we suggested specific experimental studies that might allow for the validation or rejection of the proposed immune-evasion mechanism. PMID:29619027

Invasive filamentous fungal infections associated with renal transplant tourism.

PubMed

Shoham, S; Hinestrosa, F; Moore, J; O'Donnell, S; Ruiz, M; Light, J

2010-08-01

'Transplant tourism,' the practice of traveling abroad to acquire an organ, has emerged as an issue in kidney transplantation. We treated a patient who developed invasive aspergillosis of the allograft vascular anastomosis after receiving a kidney transplant in Pakistan, prompting us to review the literature of invasive mycoses among commercial organ transplant recipients. We reviewed all published cases of infections in solid organ transplant recipients who bought their organs abroad and analyzed these reports for invasive fungal infections. Including the new case reported here, 19 cases of invasive fungal infections post commercial kidney transplant occurring in 17 patients were analyzed. Infecting organisms were Aspergillus species (12/19; 63%), Zygomycetes (5/19; 26%), and other fungi (2/19; 5%). Invasive mold infections were present at the transplanted graft in 6/17 patients (35%) with graft loss or death in 13/17 (76%) of patients and overall mortality (10/17) 59%. Invasive fungal infections, frequently originating at the graft site, have emerged as a devastating complication of commercial renal transplant and are associated with high rates of graft loss and death.

Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen Mucor circinelloides in Innate Granulomas In Vivo

PubMed Central

2018-01-01

ABSTRACT Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modeled by a combined in silico modeling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivo. In silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo. Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients. PMID:29588406

[Risk factors of invasive fungal infections in patients admitted to non- hematological oncology department and pediatric intensive care unit].

PubMed

Zhao, Cheng-song; Zhao, Shun-ying; Liu, Gang; Xi-Wei, Xu

2013-08-01

To determine risk factors of invasive fungal infections (IFI) in patients admitted to non-hematological oncology department and pediatric intensive care unit (PICU), in order to improve diagnostic level of invasive fungal infections. We retrospectively assessed 85 hospitalized pediatric patients with invasive fungal infections in Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2007 to Nov.2012. All the cases were either from non-hematological oncology department or the PICU.We reviewed risk factors of invasive fungal infections. Among 85 patients, 42 had invasive candida infection, 20 invasive aspergillus infection, 21 cryptococcus infection, 1 Histoplasma capsulatum infection and 1 Mucor mucedo infection.In the 42 patients with invasive candida infection, 5 were young infants, 3 had combined immunodeficiency, 1 cellular immunodeficiency, 25 secondary infection due to long term use of corticosteroids and/or combined use of more than 2 kinds of antibiotics with primary disease, 5 prior intestinal tract surgery or chronic diarrheal disease, 1 reflux gastritis.In the 20 patients with invasive aspergillosis infection, 10 patients had chronic granulomatous disease, 5 long term use of corticosteroids ≥ 1 month, 3 long term use of corticosteroids and combined use of more than 2 kinds of antibiotics, 2 had no apparent host factors.In the 21 patients with cryptococcus infection, 2 patients had used corticosteroids ≥ 1 month, 2 had immunodeficiency mainly for lack of antibodies, while others had no apparent host factors. The child with Mucor mucedo infection had diabetes mellitus. And the one with Histoplasma capsulatum infection had immunodeficiency. High risk factors for IFI in patients admitted to non-hematological oncology department and PICU are primary immunodeficiency disease and long term use of corticosteroids and/or long term combined use of more than 2 kinds of antibiotics. Besides, young infant is also a high risk factor for invasive candida infection. Most of the cryptococcus infections and certain aspergillosis had no obvious host factors.

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

PubMed

Imataki, O; Kami, M; Kim, S-W; Gotoh, M; Komaba, S; Kasai, M; Hashino, S; Naito, K; Masuda, M; Anan, K; Teshima, H; Togitani, K; Inoue, T; Nishimura, M; Adachi, Y; Fukuhara, T; Yamashita, T; Uike, N; Kobayashi, Y; Hamaguchi, M; Higuchi, M; Kawakami, K; Takaue, Y

2004-06-01

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Molecular detection of fungal pathogens in clinical specimens by 18S rDNA high-throughput screening in comparison to ITS PCR and culture.

PubMed

Wagner, K; Springer, B; Pires, V P; Keller, P M

2018-05-03

The rising incidence of invasive fungal infections and the expanding spectrum of fungal pathogens makes early and accurate identification of the causative pathogen a daunting task. Diagnostics using molecular markers enable rapid identification of fungi, offer new insights into infectious disease dynamics, and open new possibilities for infectious disease control and prevention. We performed a retrospective study using clinical specimens (N = 233) from patients with suspected fungal infection previously subjected to culture and/or internal transcribed spacer (ITS) PCR. We used these specimens to evaluate a high-throughput screening method for fungal detection using automated DNA extraction (QIASymphony), fungal ribosomal small subunit (18S) rDNA RT-PCR and amplicon sequencing. Fungal sequences were compared with sequences from the curated, commercially available SmartGene IDNS database for pathogen identification. Concordance between 18S rDNA RT-PCR and culture results was 91%, and congruence between 18S rDNA RT-PCR and ITS PCR results was 94%. In addition, 18S rDNA RT-PCR and Sanger sequencing detected fungal pathogens in culture negative (N = 13) and ITS PCR negative specimens (N = 12) from patients with a clinically confirmed fungal infection. Our results support the use of the 18S rDNA RT-PCR diagnostic workflow for rapid and accurate identification of fungal pathogens in clinical specimens.

[Liposomal-amphotericin B efficacy and safety].

PubMed

Hamada, Yukihiro; Komatsu, Toshiaki; Seto, Yoshinori; Matsubara, Hajime; Kume, Hikaru; Sunakawa, Keisuke; Yago, Kazuo

2010-03-01

Liposomal amphotericin B (L-AMB), a lipid-based amphotericin B formulation, has been used in Japan since June 2006 to treat fungal infection. In the 3 years since L-AMB was launched, few reports have been made on its status. To ensure its appropriate use, we restrospectively reviewed its efficacy and safety in treating fungal infections. 25 subjects with fungal infection treated with L-AMB from April 2007 until February 2008. Of those, 16 showed clinical improvement. Elevated serum creatinine occurred in 1 and decreased serum potassium in 6. We found a positive relationship between the serum potassium decrease and L-AMB dose. Logistic regression analysis of this relationship showed that serum potassium tended to fall on day 5 to 6 of L-AMB administration. While L-AMB appears highly effective in fungal infection, it requires serum potassium monitoring to ensure patient safety.

Tinea pedis and onychomycosis frequency in diabetes mellitus patients and diabetic foot ulcers. A cross sectional - observational study.

PubMed

Akkus, Gamze; Evran, Mehtap; Gungor, Dilek; Karakas, Mehmet; Sert, Murat; Tetiker, Tamer

2016-01-01

Impaired cellular immunity and reduced phagocytic function of polymorphonuclear leukocytes facilitate the development of skin fungal and bacterial infections due to uncontrolled hyperglycemia in diabetic patients. In our study, we aimed to assess onychomycosis and/or tinea pedis frequency in diabetic patients, and effects on the development of chronic complications, particularly foot ulcer. We included 227 diabetic patients in the study. Forty-three patients had diabetic foot ulcer. We screened and recorded demographic characteristics, HbA1c levels of patients, and presence of complications We examined patients dermatologically, and collected samples by scalpel from skin between toes, and from sole, toe nail, and area surrounding nails from suspected to have fungal infection. Native positivity between toes was higher in men compared to women (p<0.05). We obtained significant relation between HbA1c elevation and native positivity between toes (p<0.05). Fungal infection between toes, at sole and toe nail significantly increased in patients with diabetic foot ulcer compared to patients without diabetic foot ulcer (p<0.05). Moreover, native positivity in patients with diabetic foot ulcer correlated with presence of fungal infection examination findings (p<0.05). Fungal infections were more frequently observed in the presence of poor glycemic control and peripheral vascular disease in diabetic patients in compliance with the literature, and the presence of fungal infection may also responsible for the development of foot ulcers.

Tinea pedis and onychomycosis frequency in diabetes mellitus patients and diabetic foot ulcers. A cross sectional – observational study

PubMed Central

Akkus, Gamze; Evran, Mehtap; Gungor, Dilek; Karakas, Mehmet; Sert, Murat; Tetiker, Tamer

2016-01-01

Objective: Impaired cellular immunity and reduced phagocytic function of polymorphonuclear leukocytes facilitate the development of skin fungal and bacterial infections due to uncontrolled hyperglycemia in diabetic patients. In our study, we aimed to assess onychomycosis and/or tinea pedis frequency in diabetic patients, and effects on the development of chronic complications, particularly foot ulcer. Methods: We included 227 diabetic patients in the study. Forty-three patients had diabetic foot ulcer. We screened and recorded demographic characteristics, HbA1c levels of patients, and presence of complications We examined patients dermatologically, and collected samples by scalpel from skin between toes, and from sole, toe nail, and area surrounding nails from suspected to have fungal infection. Results: Native positivity between toes was higher in men compared to women (p<0.05). We obtained significant relation between HbA1c elevation and native positivity between toes (p<0.05). Fungal infection between toes, at sole and toe nail significantly increased in patients with diabetic foot ulcer compared to patients without diabetic foot ulcer (p<0.05). Moreover, native positivity in patients with diabetic foot ulcer correlated with presence of fungal infection examination findings (p<0.05). Conclusion: Fungal infections were more frequently observed in the presence of poor glycemic control and peripheral vascular disease in diabetic patients in compliance with the literature, and the presence of fungal infection may also responsible for the development of foot ulcers. PMID:27648034

From Biology to Drug Development: New Approaches to Combat the Threat of Fungal Biofilms

PubMed Central

Pierce, Christopher G.; Srinivasan, Anand; Ramasubramanian, Anand K.; López-Ribot, José L.

2015-01-01

Fungal infections constitute a major threat to an escalating number of critically ill patients. Fungi are eukaryotic organisms and, as such, there is a limited armamentarium of antifungal drugs, leading to high mortality rates. Moreover, fungal infections are often associated with the formation of biofilms, which contribute to virulence and further complicate treatment due to the high level of antifungal drug resistance displayed by sessile cells within these microbial communities. Thus, the treatment of fungal infections associated with a biofilm aetiology represents a formidable and unmet clinical challenge. The increasing importance and awareness of fungal biofilms is reflected by the fact that this is now an area of very active research. Studies in the last decade have provided important insights into fungal biofilm biology, physiology and pathology, as well as into the molecular basis of biofilm resistance. Here we discuss how this accumulated knowledge may inform the development of new anti-biofilm strategies and therapeutics that are urgently needed. PMID:26185082

Optimizing Prevention of Healthcare-Acquired Infections After Cardiac Surgery (HAI)_2

ClinicalTrials.gov

2017-10-24

Cardiovascular Disease; Healthcare Associated Infectious Disease; Sternal Superficial Wound Infection; Deep Sternal Infection; Mediastinitis; Thoracotomy; Conduit Harvest or Cannulation Site; Sepsis; Pneumonia

Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit.

PubMed

Aydemir, Cumhur; Onay, Huseyin; Oguz, Serife Suna; Ozdemir, Taha Resid; Erdeve, Omer; Ozkinay, Ferda; Dilmen, Ugur

2011-09-01

Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%). In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections

PubMed Central

Mackie, Joanna; Ballou, Elizabeth R.; Childers, Delma S.; MacCallum, Donna M.; Feldmann, Joerg; Brown, Alistair J. P.

2016-01-01

Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits—metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease. PMID:27362522

Mixed infections reveal virulence differences between host-specific bee pathogens.

PubMed

Klinger, Ellen G; Vojvodic, Svjetlana; DeGrandi-Hoffman, Gloria; Welker, Dennis L; James, Rosalind R

2015-07-01

Dynamics of host-pathogen interactions are complex, often influencing the ecology, evolution and behavior of both the host and pathogen. In the natural world, infections with multiple pathogens are common, yet due to their complexity, interactions can be difficult to predict and study. Mathematical models help facilitate our understanding of these evolutionary processes, but empirical data are needed to test model assumptions and predictions. We used two common theoretical models regarding mixed infections (superinfection and co-infection) to determine which model assumptions best described a group of fungal pathogens closely associated with bees. We tested three fungal species, Ascosphaera apis, Ascosphaera aggregata and Ascosphaera larvis, in two bee hosts (Apis mellifera and Megachile rotundata). Bee survival was not significantly different in mixed infections vs. solo infections with the most virulent pathogen for either host, but fungal growth within the host was significantly altered by mixed infections. In the host A. mellifera, only the most virulent pathogen was present in the host post-infection (indicating superinfective properties). In M. rotundata, the most virulent pathogen co-existed with the lesser-virulent one (indicating co-infective properties). We demonstrated that the competitive outcomes of mixed infections were host-specific, indicating strong host specificity among these fungal bee pathogens. Published by Elsevier Inc.

Epidemiological Study of Fusarium Species Causing Invasive and Superficial Fusariosis in Japan.

PubMed

Muraosa, Yasunori; Oguchi, Misato; Yahiro, Maki; Watanabe, Akira; Yaguchi, Takashi; Kamei, Katsuhiko

2017-01-01

In Japan, Fusarium species are known etiological agents of human fungal infection; however, there has been no report of a large-scale epidemiological study on the etiological agents of fusariosis. A total of 73 Fusarium isolates from patients with invasive fusariosis (IF, n= 36) or superficial fusariosis (SF, n= 37), which were obtained at hospitals located in 28 prefectures in Japan between 1998 and 2015, were used for this study. Fusarium isolates were identified using Fusarium- and Fusarium solani species complex (FSSC) -specific real-time PCR and partial DNA sequences of the elongation factor-1 alpha (EF-1α) gene and the nuclear ribosomal internal transcribed spacer (ITS) region. FSSC was predominately isolated from both patients with IF and SF (IF, 77.8% and SF, 67.6%). Distribution of the phylogenetic species of FSSC isolates from patients with IF and SF exhibited different spectra; specifically, F. keratoplasticum (FSSC 2) (25.0%) was the most frequent isolate from patients with IF, whereas F. falciforme (FSSC 3+4) (32.4%) was the most frequent isolate from patients with SF. Fusarium sp. (FSSC 5) was the second most frequent isolate from both patients with IF and SF (IF, 22.2% and SF, 24.3%). Notably, F. petroliphilum (FSSC 1) was isolated only from patients with IF. Each species was isolated from a broad geographic area, and an epidemic was not observed. This is the first epidemiological study of Fusarium species causing IF and SF in Japan.

Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?

PubMed

Parkes-Ratanshi, R; Achan, B; Kwizera, R; Kambugu, A; Meya, D; Denning, D W

2015-10-01

The HIV epidemic in Uganda has highlighted Cryptococcus and Candida infections as important opportunistic fungal infections. However, the burden of other fungal diseases is not well described. We aimed to estimate the burden of fungal infections in Uganda. All epidemiological papers of fungal diseases in Uganda were reviewed. Where there is no Ugandan data, global or East African data were used. Recurrent vaginal candidiasis is estimated to occur in 375 540 Uganda women per year; Candida in pregnant women affects up to 651,600 women per year. There are around 45,000 HIV-related oral and oesophageal candidosis cases per year. There are up to 3000 cases per year of post-TB chronic pulmonary aspergillosis. There are an estimated 40,392 people with asthma-related fungal conditions. An estimated 1,300,000 cases of tinea capitis occur in school children yearly in Uganda. There are approximately 800 HIV-positive adults with Pneumocystis jirovecii pneumonia (PJP) annually and up to 42 000 children with PJP per year. There are an estimated 4000 cryptococcal cases annually. There are an estimated 2.5 million fungal infections per year in Uganda. Cryptococcus and PJP cause around 28,000 deaths in adults and children per year. We propose replicating the model of research around cryptococcal disease to investigate and development management strategies for other fungal diseases in Uganda. © 2015 Blackwell Verlag GmbH.

Clash of kingdoms or why Drosophila larvae positively respond to fungal competitors.

PubMed

Rohlfs, Marko

2005-01-27

BACKGROUND: Competition with filamentous fungi has been demonstrated to be an important cause of mortality for the vast group of insects that depend on ephemeral resources (e.g. fruit, dung, carrion). Recent data suggest that the well-known aggregation of Drosophila larvae across decaying fruit yields a competitive advantage over mould, by which the larvae achieve a higher survival probability in larger groups compared with smaller ones. Feeding and locomotor behaviour of larger larval groups is assumed to cause disruption of fungal hyphae, leading to suppression of fungal growth, which in turn improves the chances of larval survival to the adult stage. Given the relationship between larval density, mould suppression and larval survival, the present study has tested whether fungal-infected food patches elicit communal foraging behaviour on mould-infected sites by which larvae might hamper mould growth more efficiently. RESULTS: Based on laboratory experiments in which Drosophila larvae were offered the choice between fungal-infected and uninfected food patches, larvae significantly aggregated on patches containing young fungal colonies. Grouping behaviour was also visible when larvae were offered only fungal-infected or only uninfected patches; however, larval aggregation was less strong under these conditions than in a heterogeneous environment (infected and uninfected patches). CONCLUSION: Because filamentous fungi can be deadly competitors for insect larvae on ephemeral resources, social attraction of Drosophila larvae to fungal-infected sites leading to suppression of mould growth may reflect an adaptive behavioural response that increases insect larval fitness and can thus be discussed as an anti-competitor behaviour. These observations support the hypothesis that adverse environmental conditions operate in favour of social behaviour. In a search for the underlying mechanisms of communal behaviour in Drosophila, this study highlights the necessity of investigating the role of inter-kingdom competition as a potential driving force in the evolution of spatial behaviour in insects.

Detection of Candida species by nested PCR method in one-humped camels (Camelus dromedarius).

PubMed

Parin, Ugur; Erbas, Goksel; Kirkan, Sukru; Savasan, Serap; Tugba Yuksel, H; Balat, Gamze

2018-02-01

Systemic fungal diseases are the infections caused by false treatment protocols and generally are not taken into consideration especially in the veterinary field. One-humped camels are found in the western side of the Aegean region of our country and bred for wrestling. The aim of this study is the application of diagnosing systemic fungi infection from camel blood samples by the PCR method. In this study, specific primers for DNA topoisomerase II gene sequences were used. As a result, a systemic fungal infection was detected by the nested PCR method from 10 (20%) out of 50 DNA samples taken from camels located on the western side of the Aegean region. In this study, 3 (30%) samples were identified as Candida albicans, 3 (30%) samples were identified as C. glabrata, and 4 (40%) samples were identified as C. parapsilosis. In conclusion, the 20% positive systemic fungal infection rate in one-humped camels observed in the present study showed that the systemic fungal infections are not taken into considerations in veterinary medicine. Further studies are suggested in order to obtain and to maintain extensive data for systemic fungal diseases in our country for one-humped camels.

Fungal Infections: The Stubborn Cases

PubMed Central

Adam, John E.

1982-01-01

Despite development of numerous antifungal preparations, mycotic infections persist, because of inaccurate diagnosis leading to inappropriate therapy, drug failure, non-compliance or resistance of the organism to antifungal medication. Direct KOH examination is the simplest method of proving the existence of a fungus. Fungal infections tend to be overdiagnosed; disorders which do not improve with three to four weeks of treatment should be reassessed before being labelled ‘stubborn’. Griseofulvin is effective treatment for all dermatophytes, but has certain side effects. Newer topical antifungals are also effective, but no single drug cures all fungal infections. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:20469387

Anatomy of the fasciae and fascial spaces of the maxillofacial and the anterior neck regions.

PubMed

Kitamura, Seiichiro

2018-01-01

This review provides an overview of comprehensive knowledge regarding the anatomy of the fasciae and fascial spaces of the maxillofacial and the anterior neck regions, principally from the standpoint of oral surgery, whose descriptions have long been puzzling and descriptively much too complex. The maxillofacial and the anterior neck regions are divided into four portions: the portions superficial and deep to the superficial layer of the deep cervical fascia (SfDCF) including its rostral extension to the face, the intermediate portion sandwiched by the splitting SfDCF, and the superficial portion peculiar to the face where the deep structures open on the body surface to form the oral cavity. Different fascial spaces are contained in each of the portions, although the spaces belonging to the portion of the same depth communicate freely with each other. The spaces of the superficial portions are adjacent to the oral cavity and constitute the starting point of deep infections from that cavity. The spaces of the intermediate portion lie around the mandible and occupy the position connecting the superficial and deep portions. Among these spaces, the submandibular and prestyloid spaces play an important role as relay stations conveying the infections into the deep portion. The spaces of the deep portion lie near the cervical viscera and communicate inferiorly with the superior mediastinum, among which the poststyloid space plays a role as a reception center of the infections and conveys the infections into the superior mediastinum particularly by way of the retrovisceral space and the carotid sheath.

Role of pathogen-associated molecular patterns (PAMPS) in immune responses to fungal infections.

PubMed

Taghavi, Mehdi; Khosravi, Alireza; Mortaz, Esmaeil; Nikaein, Donya; Athari, Seyyed Shamsadin

2017-08-05

Recent years have seen the rise of invasive fungal infections, which are mostly due to the increase in patients. Three major opportunistic fungal species in human are Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans that pose the biggest concern for these immunocompromised patients' mortality. The growing occurrence of opportunistic fungal infections has sparked the interest to understand defense mechanisms against pathogenic fungi. Toll-like receptors (TLRs), as a part of innate immune system, play an important role for recognizing the invading microorganisms and initiating sufficient immune responses. Recent studies have revealed an integrated role for TLR, signaling inactivating immune defense mechanisms against exact fungi. Among TLRs, TLR2 and TLR4 are the major participants in fungi recognition. The present paper highlights the role of TLR participants in fungal recognition as well as their mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Percutaneous Management of Systemic Fungal Infection Presenting As Bilateral Renal Fungal Ball

PubMed Central

Shukla, Abhishek; Shrivastava, Nitin; Singh, Chirom Amit

2016-01-01

Abstract Background: Zygomycoses are uncommon, frequently fatal diseases caused by fungi of the class Zygomycetes. The majority of human cases are caused by Mucorales (genus—rhizopus, mucor, and absidia) fungi. Renal involvement is uncommon and urine microscopy, pottasium hydroxide mount, and fungal cultures are frequently negative. Case Presentation: A twenty-one-year-old young unmarried lady presented to our emergency department with bilateral flank pain, fever, nausea, and decreased urine output of one-month duration. She was found to have azotemia with sepsis with bilateral hydronephrosis with a left renal pelvic obstructing stone. Even after nephrostomy drainage and broad spectrum antibiotics, her condition worsened. She developed disseminated fungal infection, and timely systemic antifungal followed by bilateral nephroscopic clearance saved the patient. Conclusion: Although renal fungal infections are uncommon, a high index of suspicion and early antifungal and surgical intervention can give favorable outcomes. PMID:27704055

Percutaneous Management of Systemic Fungal Infection Presenting As Bilateral Renal Fungal Ball.

PubMed

Shukla, Abhishek; Shrivastava, Nitin; Singh, Chirom Amit; Nayak, Brusabhanu

2016-01-01

Background: Zygomycoses are uncommon, frequently fatal diseases caused by fungi of the class Zygomycetes. The majority of human cases are caused by Mucorales (genus-rhizopus, mucor, and absidia) fungi. Renal involvement is uncommon and urine microscopy, pottasium hydroxide mount, and fungal cultures are frequently negative. Case Presentation: A twenty-one-year-old young unmarried lady presented to our emergency department with bilateral flank pain, fever, nausea, and decreased urine output of one-month duration. She was found to have azotemia with sepsis with bilateral hydronephrosis with a left renal pelvic obstructing stone. Even after nephrostomy drainage and broad spectrum antibiotics, her condition worsened. She developed disseminated fungal infection, and timely systemic antifungal followed by bilateral nephroscopic clearance saved the patient. Conclusion: Although renal fungal infections are uncommon, a high index of suspicion and early antifungal and surgical intervention can give favorable outcomes.

Neuroinfections caused by fungi.

PubMed

Góralska, Katarzyna; Blaszkowska, Joanna; Dzikowiec, Magdalena

2018-05-21

Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.

NUTRIENT COMPOSITION DEGRADATION OF DAPHNIA PULICARIA BY A HIGHLY PREVALENT CHYTRIDIOMYCETE FUNGAL PATHOGEN (POLYCARYUM LEAVE) DURING NATURALLY OCCURRING LAKE-WIDE EPIDEMICS.

EPA Science Inventory

Despite evidence illustrating that chytridiomycete fungal infection can be highly prevalent in Daphnia (>80%) and that infected individuals are preferentially consumed by fish, no studies have measured the nutritional consequences of using chytrid-infected Daphnia as a food sourc...

Ustilago echinata: Infection in a Mixed Martial Artist Following an Open Fracture.

PubMed

Stewart, Ethan; Waldman, Sarah; Sutton, Deanna A; Sanders, Carmita; Lindner, Jonathan; Fan, Hongxin; Wiederhold, Nathan P; Thompson, George R

2016-04-01

Ustilago, a common fungal parasite of grains, is infrequently isolated as a pathogen in humans. We describe a case of Ustilago echinata infection following an open distal tibia fracture, review the current literature of this genus as a cause of invasive fungal infection in humans, and discuss management issues.

Fungal endocarditis in paediatrics: a review of 192 cases (1971-2016).

PubMed

Ganesan, Vithiya; Ponnusamy, Shunmuga Sundaram; Sundaramurthy, Raja

2017-10-01

The aims of this article were to review the published literature on fungal endocarditis in children and to discuss the aetiology and diagnosis, with emphasis on non-invasive methods and various treatment regimes. We systematically reviewed published cases and case series of fungal endocarditis in children. We searched the literature, including PubMed and individual references for publications of original articles, single cases, or case series of paediatric fungal endocarditis, with the following keywords: "fungal endocarditis", "neonates", "infants", "child", and "cardiac vegetation". There have been 192 documented cases of fungal endocarditis in paediatrics. The highest number of cases was reported in infants (93/192, 48%) including 60 in neonates. Of the neonatal cases, 57 were premature with a median gestational age of 27 weeks and median birth weight of 860 g. Overall, 120 yeast - fungus that grows as a single cell - infections and 43 mould - fungus that grows in multicellular filaments, hyphae - infections were reported. With increasing age, there was an increased infection rate with moulds. All the yeast infections were detected by blood culture. In cases with mould infection, diagnosis was mainly established by culture or histology of emboli or infected valves after invasive surgical procedures. There have been a few recent cases of successful early diagnosis by non-invasive methods such as blood polymerase chain reaction (PCR) for moulds. The overall mortality for paediatric fungal endocarditis was 56.25%. The most important cause of death was cardiac complications due to heart failure. Among the various treatment regimens used, none of them was significantly associated with better outcome. Non-invasive methods such as PCR tests can be used to improve the chances of detecting and identifying the aetiological agent in a timely manner. Delays in the diagnosis of these infections may result in high mortality and morbidity. No significant difference was noted between combined surgical and medical therapy over exclusively combined medical therapy.

Prevalence and factors predictive of intraocular fungal infection in patients with fungemia at an academic urban tertiary care center

PubMed Central

Geraymovych, Elena; Conduff, Joseph H; Braich, Puneet S; Leffler, Christopher T; Brar, Vikram S

2015-01-01

Objective To report the prevalence and to identify factors predictive of intraocular infection in patients with fungemia receiving prophylactic antifungal therapy. Methods A retrospective review of patients who received prophylactic antifungal therapy and a dilated fundus examination at an academic urban tertiary care center from 2000 to 2007. Basic demographic information, fungal species grown, antifungal agent(s) used, number of positive blood culture specimens, visual acuity, visual symptoms, and known risks of disseminated candidiasis were noted. Logistic regression analysis was used to determine the factors significantly associated with intraocular fungal infection. Results A total of 132 patients with positive fungemia culture were requested to have ophthalmology consults. The prevalence of ocular infection was 6.9% (N=9). All nine patients were infected with Candida species. Undergoing gastrointestinal (GI) surgery within the prior 6 months was significantly related to developing intraocular infection, with an odds ratio of 18.5 (95% confidence interval, 15.1–24.3; P=0.002). Having ≥3 positive fungal blood cultures was also a significant risk factor, with an odds ratio of 2.6 (95% confidence interval, 1.8–3.7; P=0.03). Among 40 patients having GI surgery, eight (20.0%) had intraocular fungal disease, compared with one of 92 patients (1.1%) not having GI surgery. Among 125 patients with a negative baseline examination result, two of 32 patients (6.3%), who had recent GI surgery, subsequently developed fungal ocular disease, compared with 0 of 93 patients (0%), who did not have recent GI surgery. Conclusion Recent GI surgery and higher numbers of positive fungal blood culture specimens may be predictive of candida ocular infections. Normal baseline fundoscopy examination results in patients with such risks may require repeat evaluations to detect delayed manifestations. PMID:26491246

Deep Invasive Fungal Infection of the Hand in a Child Mimicking a Local Gigantism.

PubMed

Chatterjee, Anirban; Chatterjee, Shamita

2018-04-01

Subcutaneous and deep fungal infections in the hand are rare among children. These are usually found in immunocompromised adults or in persons engaged in soil handling activities, due to direct exposure, especially in the tropics. Delay in diagnosis is usual because pyogenic and other granulomatous infections are considered first. The authors present the case of a healthy, immunocompetent 2½-year-old child who presented with progressive swelling of the right hand mimicking a localized gigantism of the entire hand. Multiple operative drainage procedures done previously had failed to resolve the condition. A biopsy established the presence of fungal hyphae, thus confirming the diagnosis of deep fungal infection of the hand and guided proper therapeutic intervention. A strong index of suspicion needs to be maintained in cases not responding to conventional antibacterial therapy, and both microbiologic and histopathologic samples need to be obtained to establish the diagnosis.

Developing collaborative works for faster progress on fungal respiratory infections in cystic fibrosis.

PubMed

Schwarz, Carsten; Vandeputte, Patrick; Rougeron, Amandine; Giraud, Sandrine; Dugé de Bernonville, Thomas; Duvaux, Ludovic; Gastebois, Amandine; Alastruey-Izquierdo, Ana; Martín-Gomez, Maria Teresa; Mazuelos, Estrella Martin; Sole, Amparo; Cano, Josep; Pemán, Javier; Quindos, Guillermo; Botterel, Françoise; Bougnoux, Marie-Elisabeth; Chen, Sharon; Delhaès, Laurence; Favennec, Loïc; Ranque, Stéphane; Sedlacek, Ludwig; Steinmann, Joerg; Vazquez, Jose; Williams, Craig; Meyer, Wieland; Le Gal, Solène; Nevez, Gilles; Fleury, Maxime; Papon, Nicolas; Symoens, Françoise; Bouchara, Jean-Philippe

2018-04-01

Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.

Knowing your neighbourhood—the effects of Epichloë endophytes on foliar fungal assemblages in perennial ryegrass in dependence of season and land-use intensity

PubMed Central

Guerreiro, Marco Alexandre; Peršoh, Derek; Begerow, Dominik; Krauss, Jochen

2018-01-01

Epichloë endophytes associated with cool-season grass species can protect their hosts from herbivory and can suppress mycorrhizal colonization of the hosts’ roots. However, little is known about whether or not Epichloë endophyte infection can also change the foliar fungal assemblages of the host. We tested 52 grassland study sites along a land-use intensity gradient in three study regions over two seasons (spring vs. summer) to determine whether Epichloë infection of the host grass Lolium perenne changes the fungal community structure in leaves. Foliar fungal communities were assessed by Next Generation Sequencing of the ITS rRNA gene region. Fungal community structure was strongly affected by study region and season in our study, while land-use intensity and infection with Epichloë endophytes had no significant effects. We conclude that effects on non-systemic endophytes resulting from land use practices and Epichloë infection reported in other studies were masked by local and seasonal variability in this study’s grassland sites. PMID:29780665

Genome‐wide gene expression dynamics of the fungal pathogen Dothistroma septosporum throughout its infection cycle of the gymnosperm host Pinus radiata

PubMed Central

Guo, Yanan; Sim, Andre D.; Kabir, M. Shahjahan; Chettri, Pranav; Ozturk, Ibrahim K.; Hunziker, Lukas; Ganley, Rebecca J.; Cox, Murray P.

2015-01-01

Summary We present genome‐wide gene expression patterns as a time series through the infection cycle of the fungal pine needle blight pathogen, Dothistroma septosporum, as it invades its gymnosperm host, Pinus radiata. We determined the molecular changes at three stages of the disease cycle: epiphytic/biotrophic (early), initial necrosis (mid) and mature sporulating lesion (late). Over 1.7 billion combined plant and fungal reads were sequenced to obtain 3.2 million fungal‐specific reads, which comprised as little as 0.1% of the sample reads early in infection. This enriched dataset shows that the initial biotrophic stage is characterized by the up‐regulation of genes encoding fungal cell wall‐modifying enzymes and signalling proteins. Later necrotrophic stages show the up‐regulation of genes for secondary metabolism, putative effectors, oxidoreductases, transporters and starch degradation. This in‐depth through‐time transcriptomic study provides our first snapshot of the gene expression dynamics that characterize infection by this fungal pathogen in its gymnosperm host. PMID:25919703

The place for itraconazole in treatment.

PubMed

Maertens, Johan; Boogaerts, Marc

2005-09-01

The incidence of systemic fungal infections has risen sharply in the last two decades, reflecting a rise in the number of patients who are predisposed to these diseases because they are immunosuppressed or immunocompromised. The growing use of intensive chemotherapy to treat cancer, highly immunosuppressive drug regimens (not only in transplant recipients), widespread prophylactic or empirical broad-spectrum antibiotics, prolonged parenteral nutrition, long-term indwelling lines, improved survival in neonatal and other intensive care units, together with the AIDS epidemic have led to an upsurge in the number of patients at risk. In addition, there have been changes in the epidemiology of systemic fungal infections, with Aspergillus spp. and Candida spp. other than Candida albicans becoming increasingly common causes. These changes have affected the selection of drugs for first-line or prophylactic use, as not all agents have the critical spectrum of activity required. The management of systemic fungal infections can be divided into four main strategies: prophylaxis, early empirical use, pre-emptive and definite therapy. Antifungal prophylaxis is given based on the patient risk factors, but in the absence of infection. Empirical antifungal therapy is given in patients at risk with signs of infection of unclear aetiology (usually persistent fever) but of possible fungal origin. Therapy is given pre-emptively in patients at risk with additional evidence for the presence of an infective agent in a way predisposing for infection (e.g. Aspergillus colonization; high Candida colonization index). Finally, definite treatment is used in patients with confirmed fungal infection. The distinction between risk-adapted prophylaxis, early empirical therapy, and pre-emptive use of antifungals often becomes unclear and clinical decision making depends largely on local epidemiology and resistance patterns, adequate definition of patient risk categories, early diagnosis and the calculation of cost-benefit ratios. This article addresses the use of itraconazole in the treatment of invasive fungal infections in the haematology patient.

Fungal infections in adult patients on extracorporeal life support.

PubMed

Cavayas, Yiorgos Alexandros; Yusuff, Hakeem; Porter, Richard

2018-04-17

Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit. They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction. These factors are thought to predispose them to fungal infections. We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO. We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers. We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture. Our study comprised 2129 adult patients (10.8%) with fungal colonization or infection. Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge. There were 245 patients (1.2%) with Candida invasive bloodstream infection, with 35.9% survival. Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p < 0.001), and influenza infection (OR 2.48; p < 0.001). Risk factors for candidemia included sepsis (OR 1.60; p = 0.005) and renal replacement therapy (OR 1.55; p = 0.007). In multivariable analysis, Aspergillus involvement (OR 0.40; p < 0.001) and candidemia (OR 0.47; p < 0.001) were both independently associated with decreased survival. The prevalence of Aspergillus involvement and Candida invasive bloodstream infection were not higher in patients on ECMO than what has been reported in the general intensive care population. Both were independently associated with a reduced survival. Aspergillus involvement was strongly associated with ECMO for respiratory support and influenza.

Comparison of Non-Culture-Based Methods for Detection of Systemic Fungal Infections, with an Emphasis on Invasive Candida Infections

PubMed Central

White, P. Lewis; Archer, Alice E.; Barnes, Rosemary A.

2005-01-01

The accepted limitations associated with classic culture techniques for the diagnosis of invasive fungal infections have lead to the emergence of many non-culture-based methods. With superior sensitivities and quicker turnaround times, non-culture-based methods may aid the diagnosis of invasive fungal infections. In this review of the diagnostic service, we assessed the performances of two antigen detection techniques (enzyme-linked immunosorbent assay [ELISA] and latex agglutination) with a molecular method for the detection of invasive Candida infection and invasive aspergillosis. The specificities for all three assays were high (≥97%), although the Candida PCR method had enhanced sensitivity over both ELISA and latex agglutination with values of 95%, 75%, and 25%, respectively. However, calculating significant sensitivity values for the Aspergillus detection methods was not feasible due to a low number of proven/probable cases. Despite enhanced sensitivity, the PCR method failed to detect nucleic acid in a probable case of invasive Candida infection that was detected by ELISA. In conclusion, both PCR and ELISA techniques should be used in unison to aid the detection of invasive fungal infections. PMID:15872239

Bacterial diseases of the skin.

PubMed

Edlich, Richard F; Winters, Kathryne L; Britt, L D; Long, William B

2005-01-01

When considering common bacterial diseases of the skin, rather distinct clinical responses to a variety of bacterial infections have been identified. In these cases, it is the specific site of infection and the attendant inflammatory responses that provide the characteristic clinical picture. When the pyoderma extends just below the stratum corneum, it is called impetigo. Nonbullous impetigo is the most common pediatric skin infection. It usually starts in a traumatized area. The typical lesion begins as an erythematous papule, after which it becomes a unilocular vesicle. When the subcorneal vesicle becomes pustular, it ruptures and eventually becomes a yellow, golden crust that is a hallmark of the disease process. Bullous impetigo is a less common form of impetigo, accounting for fewer than 30% of all impetigo cases. It occurs in infants and is characterized by rapid progression of vesicles to the formation of bullae measuring larger than 5 mm in diameter in previously untraumatized skin. Treatment of nonbullous impetigo must include intervention against the pathogen as well as improvements in the hygiene and living conditions of the patient. A fundamental tenet is to debride the crust (scab) from the wound surface using poloxamer 188. If the lesions are not widespread, topical mupirocin is the treatment of choice. Treatment of bullous impetigo is similar, except that the local cleansing and topical antibiotic must be complemented by systemic antibiotics if there is evidence of disseminating infections. Ecthyma is usually a consequence of failure to treat effectively impetigo. The untreated infection extends deep into the tissue in shallow ulcerations that often heal without scar. Treatment for ecthyma usually requires systemic antibiotics against either staphylococcus or streptococcus. Folliculitis is a pyoderma located within a hair follicle, secondary to follicular occlusion by keratin, overhydration, or either bacterial or fungal infection. Folliculitis may be divided into either a deep or a superficial type. In the superficial type, the pustule is located at the opening of the hair follicle. In the deep form, the infection may extend beyond the confines of the hair follicle, becoming a furuncle or boil. Carbuncles are aggregates of interconnected furuncles that drain through multiple openings of the skin. Treatment of folliculitis must include searching for and avoiding any factors predisposing to infection. If topical antibiotic therapy is ineffective in controlling the infection, surgical drainage of the infected skin abscess will be necessary. Paronychia is the most common bacterial infection of the hand, which often requires surgical incisional drainage. Similarly, a felon that is an infection of the distal pulp of a finger usually requires surgical drainage. Finally, cellulitis is an acute inflammatory reaction involving the skin and underlying subcutaneous tissue. It usually starts as erysipelas and may advance to lymphangitis, lymphadenitis, or gangrene,which will respond to life-saving interventions in the hospital that usually include systemic antibiotic treatment as well as surgical intervention.

Burden of fungal infections in Algeria.

PubMed

Chekiri-Talbi, M; Denning, D W

2017-06-01

We report for the first time in Algeria and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the National Office of Statistics (Office National des Statistiques: ONS), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants, and probably at least 568,900 (1.41%) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems, as there are over 1 million adult asthmatics. Candidaemia is estimated in 2,020 people, invasive aspergillosis in 2,865 people, and intra-abdominal candidiasis in 303 people; these are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer including 1,500 in children), nor is COPD (an estimated 317,762 patients, of whom 20.3% are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria.

The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida albicans Cells

PubMed Central

Degani, Genny; Fonzi, William A.

2017-01-01

Candida albicans is an opportunistic microorganism that can become a pathogen causing mild superficial mycosis or more severe invasive infections that can be life-threatening for debilitated patients. In the etiology of invasive infections, key factors are the adaptability of C. albicans to the different niches of the human body and the transition from a yeast form to hypha. Hyphal morphology confers high adhesiveness to the host cells, as well as the ability to penetrate into organs. The cell wall plays a crucial role in the morphological changes C. albicans undergoes in response to specific environmental cues. Among the different categories of enzymes involved in the formation of the fungal cell wall, the GH72 family of transglycosylases plays an important assembly role. These enzymes cut and religate β-(1,3)-glucan, the major determinant of cell shape. In C. albicans, the PHR family encodes GH72 enzymes, some of which work in specific environmental conditions. In this review, we will summarize the work from the initial discovery of PHR genes to the study of the pH-dependent expression of PHR1 and PHR2, from the characterization of the gene products to the recent findings concerning the stress response generated by the lack of GH72 activity in C. albicans hyphae. PMID:29371575

[Clinically documented fungal infections].

PubMed

Kakeya, Hiroshi; Kohno, Shigeru

2008-12-01

Proven fungal infections are diagnosed by histological/microbiological evidence of fungi at the site of infection and positive blood culture (fungemia). However, invasive diagnosing examinations are not always applied for all of immunocompromised patients. Clinically documented invasive fungal infections are diagnosed by typical radiological findings such as halo sign on chest CT plus positive serological/molecular evidence of fungi. Serological tests of Aspergillus galactomannan antigen and beta-glucan for aspergillosis and cryptococcal glucuronoxylomannan antigen for cryptococcosis are useful. Hence, none of reliable serological tests for zygomycosis are available so far. In this article, risk factors, sign and symptoms, and diagnostic methods for clinically documented cases of invasive aspergillosis, pulmonary cryptococcosis, and zygomycosis with diabates, are reviewed.

Evaluation of Novel Antimicrobial Peptides as Topical Anti-Infectives with Broad Spectrum Activity Against Combat-Related Bacterial and Fungal Wound Infections

DTIC Science & Technology

2016-10-01

absence of topical antibiotics, are immediately colonized by gram -positive skin flora, such as Staphylococcus aureus. Gram -negative bacteria such as...complications. Silver sulfadiazine is not active against fungal infections,4 and its side effects include staining of the treated burn wound, allergic

Behavior Performance of Diuraphis noxia (Homoptera: Aphididae) on Fungal Endophyte-Infected and Uninfected Perennial Ryegrass

Treesearch

S.L. Clement; D.G. Lester; A. Dan Wilson; K.S. Pike

1992-01-01

The behavior and performance of the Russian wheat aphid, Diuraphis noxia (Mordvilko), on fungal endophyte-infected and endophyte-free perennial ryegrass, Lolium perenne L., was investigated in the laboratory and field. Aphids did not select endophyte-free over endophyte-infected leaf sheaths and stem segments in petri dish preference tests....

Terbinafine

MedlinePlus

... to treat fungal infections of the scalp. Terbinafine tablets are used to treat fungal infections of the ... Terbinafine comes as granules and as a tablet to take by mouth. Terbinafine granules are usually taken with a soft food once a day for 6 weeks. Terbinafine tablets are usually ...

The Arabidopsis miR396 mediates pathogen-associated molecular pattern-triggered immune responses against fungal pathogens

PubMed Central

Soto-Suárez, Mauricio; Baldrich, Patricia; Weigel, Detlef; Rubio-Somoza, Ignacio; San Segundo, Blanca

2017-01-01

MicroRNAs (miRNAs) play a pivotal role in regulating gene expression during plant development. Although a substantial fraction of plant miRNAs has proven responsive to pathogen infection, their role in disease resistance remains largely unknown, especially during fungal infections. In this study, we screened Arabidopsis thaliana lines in which miRNA activity has been reduced using artificial miRNA target mimics (MIM lines) for their response to fungal pathogens. Reduced activity of miR396 (MIM396 plants) was found to confer broad resistance to necrotrophic and hemibiotrophic fungal pathogens. MiR396 levels gradually decreased during fungal infection, thus, enabling its GRF (GROWTH-REGULATING FACTOR) transcription factor target genes to trigger host reprogramming. Pathogen resistance in MIM396 plants is based on a superactivation of defense responses consistent with a priming event during pathogen infection. Notably, low levels of miR396 are not translated in developmental defects in absence of pathogen challenge. Our findings support a role of miR396 in regulating plant immunity, and broaden our knowledge about the molecular players and processes that sustain defense priming. That miR396 modulates innate immunity without growth costs also suggests fine-tuning of miR396 levels as an effective biotechnological means for protection against pathogen infection. PMID:28332603

Life histories of hosts and pathogens predict patterns in tropical fungal plant diseases.

PubMed

García-Guzmán, Graciela; Heil, Martin

2014-03-01

Plant pathogens affect the fitness of their hosts and maintain biodiversity. However, we lack theories to predict the type and intensity of infections in wild plants. Here we demonstrate using fungal pathogens of tropical plants that an examination of the life histories of hosts and pathogens can reveal general patterns in their interactions. Fungal infections were more commonly reported for light-demanding than for shade-tolerant species and for evergreen rather than for deciduous hosts. Both patterns are consistent with classical defence theory, which predicts lower resistance in fast-growing species and suggests that the deciduous habit can reduce enemy populations. In our literature survey, necrotrophs were found mainly to infect shade-tolerant woody species whereas biotrophs dominated in light-demanding herbaceous hosts. Far-red signalling and its inhibitory effects on jasmonic acid signalling are likely to explain this phenomenon. Multiple changes between the necrotrophic and the symptomless endophytic lifestyle at the ecological and evolutionary scale indicate that endophytes should be considered when trying to understand large-scale patterns in the fungal infections of plants. Combining knowledge about the molecular mechanisms of pathogen resistance with classical defence theory enables the formulation of testable predictions concerning general patterns in the infections of wild plants by fungal pathogens. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Think fungus NOT just a crypto-meningitis in AIDS!

PubMed

Badiye, Amit; Patnaik, Mrinal; Deshpande, Alaka; Rajendran, C; Chandrashekara, K V

2012-12-01

Extrapulmonary cryptococcosis has been defined as AIDS defining illness in HIV infected people. Cryptococcal meningitis is the commonest meningitis with advanced immune deficiency. Therefore clinicians ask for tests only for detection of cryptococci which may be misleading. A prospective study of suspected fungal meningitis with CSF fungal culture is carried out. 70 ART naive cases of suspected fungal meningitis in HIV cases were subjected to CSF cytochemistry, smear exam and CSF fungal culture. The CSF culture was positive in 75.6% cases of these 21 were C. Neoformans as against 28 of Rhodotorula. In addition candida, aspergillus, geotrichum, trichosporon were isolated. Apart from c. neoformans, other fungi also cause meningitis. Each case of suspected fungal meningitis, may be subjected for CSF fungal culture for proper and adequate management. If facility for fungal culture is not available and if CSF smear shows evidence of fungal infection then standard therapy with Amphotericin may be instituted earlier to reduce mortality. This is the largest series isolating Rhodotorula from CSF in AIDS patients.

Discrimination of fungal infections on grape berries via spectral signatures

NASA Astrophysics Data System (ADS)

Molitor, Daniel; Griesser, Michaela; Schütz, Erich; Khuen, Marie-Therese; Schefbeck, Christa; Ronellenfitsch, Franz Kai; Schlerf, Martin; Beyer, Marco; Schoedl-Hummel, Katharina; Anhalt, Ulrike; Forneck, Astrid

2016-04-01

The fungal pathogens Botrytis cinerea and Penicillium expansum are causing economic damages on grapevine worldwide. Especially the simultaneous occurrence of both often results in off-flavours highly threatening wine quality. For the classification of grape quality as well as for the determination of targeted enological treatments, the knowledge of the level of fungal attack is of highest interest. However, visual assessment and pathogen discrimination are cost-intensive. Consequently, a pilot laboratory study aimed at (i) detecting differences in spectral signatures between grape berry lots with different levels of infected berries (B. cinerea and/or P. expansum) and (ii) detecting links between spectral signatures and biochemical as well as quantitative molecular markers for fungal attack. To this end, defined percentages (infection levels) of table grape berries were inoculated with fungal spore suspensions. Spectral measurements were taken using a FieldSpec 3 Max spectroradiometer (ASD Inc., Boulder/Colorado, USA) in regular intervals after inoculation. In addition, fungal attack was determined enzymatically) and quantitatively (real-time PCR). In addition, gluconic acid concentrations (as a potential markers for fungal attack) were determined photometrically. Results indicate that based on spectral signatures, a discrimination of P. expansum and B. cinerea infections as well as of different B. cinerea infection levels is possible. Real-time PCR analyses, detecting DNA levels of both fungi, showed yet a low detection level. Whereas the gluconic acid concentrations turned out to be specific for the two fungi tested (B. cinerea vs. P. expansum) and thus may serve as a differentiating biochemical marker. Correlation analyses between spectral measurements and biological data (gluconic acid concentrations, fungi DNA) as well as further common field and laboratory trials are targeted.

Heat-Killed Yeast as a Pan-Fungal Vaccine.

PubMed

Martinez, Marife; Clemons, Karl V; Stevens, David A

2017-01-01

Fungal infections continue to rise worldwide. Antifungal therapy has long been a mainstay for the treatment of these infections, but often can fail for a number of reasons. These include acquired or innate drug resistance of the causative agent, poor drug penetration into the affected tissues, lack of cidal activity of the drug and drug toxicities that limit therapy. In some instances, such as coccidioidal meningitis, therapy is life-long. In addition, few new antifungal drugs are under development. In light of this information a preventative vaccine is highly desirable. Although numerous investigators have worked toward the development of fungal vaccines, none have become commercially available for use in humans. In the course of our studies, we have discovered that heat-killed yeast (HKY) of Saccharomyces cerevisiae can be used as a vaccine and have shown that it has efficacy in the prevention and reduction of five different fungal infections when used experimentally in mice, which raises the possibility of a pan-fungal vaccine preparation. In our studies we grow S. cerevisiae in broth and heat-kill the organism at 70 ° C for 3 h. The number of dead yeast cells is adjusted and mice are vaccinated subcutaneously beginning 3-7 weeks prior to infection. After infection, efficacy is assessed on the basis of survival and residual burden of the fungus in the target organs. Alternatively, efficacy can be assessed solely on fungal burden at a predetermined time postinfection. Although itself it is unlikely to be moved toward commercialization, HKY can be used a positive control vaccine for studies on specific molecular entities as vaccines, and as a guidepost for the key elements of potential, more purified, pan-fungal vaccine preparations.

Identification of Putative Coffee Rust Mycoparasites via Single-Molecule DNA Sequencing of Infected Pustules

PubMed Central

Marino, John A.; Perfecto, Ivette; Vandermeer, John

2015-01-01

The interaction of crop pests with their natural enemies is a fundament to their control. Natural enemies of fungal pathogens of crops are poorly known relative to those of insect pests, despite the diversity of fungal pathogens and their economic importance. Currently, many regions across Latin America are experiencing unprecedented epidemics of coffee rust (Hemileia vastatrix). Identification of natural enemies of coffee rust could aid in developing management strategies or in pinpointing species that could be used for biocontrol. In the present study, we characterized fungal communities associated with coffee rust lesions by single-molecule DNA sequencing of fungal rRNA gene bar codes from leaf discs (≈28 mm2) containing rust lesions and control discs with no rust lesions. The leaf disc communities were hyperdiverse in terms of fungi, with up to 69 operational taxonomic units (putative species) per control disc, and the diversity was only slightly reduced in rust-infected discs, with up to 63 putative species. However, geography had a greater influence on the fungal community than whether the disc was infected by coffee rust. Through comparisons between control and rust-infected leaf discs, as well as taxonomic criteria, we identified 15 putative mycoparasitic fungi. These fungi are concentrated in the fungal family Cordycipitaceae and the order Tremellales. These data emphasize the complexity of diverse fungi of unknown ecological function within a leaf that might influence plant disease epidemics or lead to the development of species for biocontrol of fungal disease. PMID:26567299

Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick

PubMed Central

de Groot, Piet W. J.; Bader, Oliver; de Boer, Albert D.; Weig, Michael

2013-01-01

Understanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host tissue or abiotic medical devices are critical for colonization leading to invasion and damage of host tissue. Here, with a main focus on pathogenic Candida species, we summarize recent progress made in the field of adhesins in human fungal pathogens and underscore the importance of these proteins in establishment of fungal diseases. PMID:23397570

Sterile compounding: clinical, legal, and regulatory implications for patient safety.

PubMed

Qureshi, Nabeel; Wesolowicz, Laurie; Stievater, Trish; Lin, Alexandra Tungol

2014-12-01

Poor compounding practices by the New England Compounding Center resulted in the 2012-2013 fungal infections outbreak. Contaminated injectable methylprednisolone led to the diagnosis of fungal infections in 751 patients and 64 deaths. In the United States, pharmacy compounding has traditionally been regulated by state boards of pharmacy rather than the FDA. To minimize safety risks related to pharmacy compounding, the Drug Quality and Security Act (DQSA) was signed into law November 27, 2013, to improve regulation of compounding pharmacies. To (a) review the literature regarding clinical, legal, and regulatory implications of pharmacy compounding for patient safety during the 2012-2013 fungal infections outbreak and (b) discuss strategies that managed care organizations (MCOs) can use to promote safe compounding practices.  A literature search was conducted via PubMed for original articles on fungal infections related to drug compounding published October 2012 to March 2014. Specific search terms included "drug compounding and fungal infection" and "fungal meningitis outbreak." The FDA website was also utilized for material related to the Food, Drug, and Cosmetic Act and the DQSA.  Four articles met inclusion criteria. The 2012-2013 fungal infections outbreak was attributed to 3 lots of preservative-free methylprednisolone acetate, which comprised 17,675 vials distributed to 76 facilities across 23 states. Median incubation period (from time of last injection to initial diagnosis) was 47 days, ranging from 0 to 249 days. According to the FDA, a total of 30 recalls regarding compounded products were issued by pharmacies during March through December 2013. Pharmacy compounding has the potential for significant safety risks. The purpose of the DQSA is to improve regulation of compounding pharmacies. Since registration as an outsourcing facility is voluntary, uncertainty still remains regarding advancement in safe compounding practices. MCOs can employ multiple strategies to ensure patient safety and promote appropriate drug therapy.

Serious fungal infections in Ecuador.

PubMed

Zurita, J; Denning, D W; Paz-Y-Miño, A; Solís, M B; Arias, L M

2017-06-01

There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

Experimental infection of snakes with Ophidiomyces ophiodiicola causes pathological changes that typify snake fungal disease

USGS Publications Warehouse

Lorch, Jeffrey M.; Lankton, Julia S.; Werner, Katrien; Falendysz, Elizabeth A.; McCurley, Kevin; Blehert, David S.

2015-01-01

IMPORTANCE Skin infections in snakes, referred to as snake fungal disease (SFD), have been reported with increasing frequency in wild snakes in the eastern United States. While most of these infections are associated with the fungusOphidiomyces ophiodiicola, there has been no conclusive evidence to implicate this fungus as a primary pathogen. Furthermore, it is not understood why the infections affect different host populations differently. Our experiment demonstrates that O. ophiodiicola is the causative agent of SFD and can elicit pathological changes that likely impact fitness of wild snakes. This information, and the laboratory model we describe, will be essential in addressing unresolved questions regarding disease ecology and outcomes of O. ophiodiicola infection and helping to conserve snake populations threatened by the disease. The SFD model of infection also offers utility for exploring larger concepts related to comparative fungal virulence, host response, and host-pathogen evolution.

Polymeric Interventions for Microbial Infections: A Review.

PubMed

Hutnick, Melanie A; Pokorski, Jonathan K

2018-05-22

The world is facing a growing crisis of microbial infections, where resistant strains are rapidly outpacing the development of new therapeutics. In an effort to combat this, the polymer community is developing new ways to improve upon drug delivery, synthesizing novel antimicrobial polymers, and using polymer technology to harness combination therapies. This review focuses primarily on the use of polymers to treat both bacterial and fungal infections in recent years. A bevy of work has illustrated that polymer technologies can have a huge impact in treating bacterial infections. However, harnessing polymers to deliver antifungals or as stand-alone therapeutics lags far behind that of interventions for bacterial infections. Fungal infections can be crippling to both human health and the agricultural community, making this area ripe for drug delivery technologies. This review describes recent work and highlights opportunities for bacterial and fungal treatment using soft matter.

Hyperthyroidism secondary to disseminated mucormycosis in a child with acute lymphoblastic leukemia: case report and a review of published reports.

PubMed

Irga, Ninela; Kosiak, Wojciech; Jaworski, Radoslaw; Komarnicka, Jolanta; Birkholz, Dorota

2013-02-01

Thyroiditis due to fungal infection is an extremely rare cause of hyperthyroidism. The most common etiological factor of thyroiditis is Aspergillus. Infections due to members of the Mucorales have been an increasing clinical problem in recent years, and the prognosis in generalized infections due to those fungi is usually very poor. No hyperthyroidism in a child with thyroiditis due to mucormycosis has been reported in the literature so far. We describe a clinical course of generalized mucormycosis with thyroid involvement in a 12-year-old girl treated for acute lymphoblastic leukemia. The child underwent a hyperthyroidism connected with thyroid involvement due to a fungal process. The diagnosis was based on the clinical signs, laboratory findings and typical ultrasound scan; however, later attempt to amplify the fungi DNA from the tissue block has failed. The child died because of multiorgan failure due to general fungal infection 49 days after the invasive fungal infection was diagnosed. The generalized mucormycosis is always connected with poor prognosis and the mortality is high.

Fungal Biofilms: In vivo models for discovery of anti-biofilm drugs

PubMed Central

Nett, Jeniel E.; Andes, David

2015-01-01

SUMMARY During infection, fungi frequently transition to a biofilm lifestyle, proliferating as communities of surface-adherent aggregates of cells. Phenotypically, cells in a biofilm are distinct from free-floating cells. Their high tolerance of antifungals and ability to withstand host defenses are two characteristics that foster resilience. Biofilm infections are particularly difficult to eradicate and most available antifungals have minimal activity. Therefore, the discovery of novel compounds and innovative strategies to treat fungal biofilms is of great interest. Although many fungi have been observed to form biofilms, the most well-studied is Candida albicans. Animal models have been developed to simulate common Candida device-associated infections, including those involving vascular catheters, dentures, urinary catheters, and subcutaneous implants. Models have also reproduced the most common mucosal biofilm infections, oropharyngeal and vaginal candidiasis. These models incorporate the anatomical site, immune components, and fluid dynamics of clinical niches and have been instrumental in the study of drug resistance and investigation of novel therapies. This chapter describes the significance of fungal biofilm infections, the animal models developed for biofilm study, and how these models have contributed to development of new strategies for eradication of fungal biofilm infections. PMID:26397003

Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients. Multicentre Study Group.

PubMed

Presterl, E; Graninger, W

1994-04-01

In a non-comparative multicentre trial 51 patients aged 24 days to 17 years received treatment with intravenous or oral fluconazole for suspected systemic fungal infections. Twenty-seven patients had confirmed infections, 26 being confirmed mycologically and 1 histologically. All isolates were Candida species. Of the 43 clinically assessed patients, 30 were considered cured, 7 improved and 6 experienced failure of therapy. Of 27 patients with confirmed fungal infections, 25 were assessed mycologically and all but one were considered cured. Of the six patients experiencing clinical failure, two had a confirmed infection and only one of these experienced mycological failure. This patient had a primary diagnosis of candidemia with persistence of Candida albicans and Candida parapsilosis. All 51 patients were evaluable for safety. No treatment-related adverse events required termination of treatment. Treatment-related side effects (diarrhea, vomiting, deafness) were reported by three of 51 patients, three patients had laboratory test abnormalities possibly related to fluconazole treatment, including elevation of liver enzyme levels and of the eosinophil count. Results of this study confirm the efficacy and safety of fluconazole in the treatment of pediatric patients with severe fungal infection.

Fungal Biofilms: In Vivo Models for Discovery of Anti-Biofilm Drugs.

PubMed

Nett, Jeniel E; Andes, David R

2015-06-01

During infection, fungi frequently transition to a biofilm lifestyle, proliferating as communities of surface-adherent aggregates of cells. Phenotypically, cells in a biofilm are distinct from free-floating cells. Their high tolerance of antifungals and ability to withstand host defenses are two characteristics that foster resilience. Biofilm infections are particularly difficult to eradicate, and most available antifungals have minimal activity. Therefore, the discovery of novel compounds and innovative strategies to treat fungal biofilms is of great interest. Although many fungi have been observed to form biofilms, the most well-studied is Candida albicans. Animal models have been developed to simulate common Candida device-associated infections, including those involving vascular catheters, dentures, urinary catheters, and subcutaneous implants. Models have also reproduced the most common mucosal biofilm infections: oropharyngeal and vaginal candidiasis. These models incorporate the anatomical site, immune components, and fluid dynamics of clinical niches and have been instrumental in the study of drug resistance and investigation of novel therapies. This chapter describes the significance of fungal biofilm infections, the animal models developed for biofilm study, and how these models have contributed to the development of new strategies for the eradication of fungal biofilm infections.

Animal models: an important tool in mycology.

PubMed

Capilla, Javier; Clemons, Karl V; Stevens, David A

2007-12-01

Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.

Incidence and Outcomes of Positive Donor Corneoscleral Rim Fungal Cultures after Keratoplasty.

PubMed

Vislisel, Jesse M; Goins, Kenneth M; Wagoner, Michael D; Schmidt, Gregory A; Aldrich, Benjamin T; Skeie, Jessica M; Reed, Cynthia R; Zimmerman, M Bridget; Greiner, Mark A

2017-01-01

To determine the incidence of positive corneoscleral donor rim fungal cultures after keratoplasty and to report clinical outcomes of grafts with culture-positive donor rims. Retrospective cohort study. Consecutive donor corneas and keratoplasty recipients at a single tertiary referral center over 20 years. Patient charts were reviewed to determine the incidence of positive donor rim fungal cultures and clinical outcomes of all grafts using contaminated tissue. The primary outcome measures were positive donor rim fungal culture results and the development of postkeratoplasty fungal infection using corresponding corneal tissue. The secondary outcome measure was the impact of postoperative prophylaxis on donor tissue-associated infections. A total of 3414 keratoplasty cases were included in the statistical analysis. Seventy-one cases (2.1%) were associated with a fungal culture-positive donor rim. Candida species were cultured in 40 cases (56.3%). There was a higher incidence of positive rim cultures over the last 5 years of the analytic period compared with the first 15 years (P = 0.018). Fungal keratitis developed in 4 cases (5.6%), and all patients required further surgical intervention to achieve cure. There were no cases of fungal endophthalmitis. Empiric antimycotic prophylaxis initiated at the time of positive culture result reduced the incidence of keratitis from 15.8% in untreated cases to 1.9% in treated cases (P = 0.056). Positive donor rim fungal cultures are uncommon, but carry an unacceptably high risk of postoperative fungal infection. This risk may be reduced with prophylactic antimycotic therapy when culture-positive donor rims are identified. Copyright © 2016 American Academy of Ophthalmology. All rights reserved.

Neonatal sepsis due to vertical transmission from maternal genital tract.

PubMed

Ayengar, V; Madhulika; Vani, S N

1991-01-01

High vaginal swabs (HVS) of 1792 expectant mothers were sent for culture at the time of delivery, prior to first vaginal examination. The newborns were followed-up for development of superficial or deep infections. Appropriate cultures of the babies who developed infections were sent. Bacterial growth of predominantly gram-ve organisms was obtained in 1026 (57%) HVS. Infection developed in 48 (27%) babies in 1st 72 hours of life, of which 28 had deep infection while the rest had superficial infection. Vertical transmission of organisms was documented in 24 (1.3%) mother-baby dyads and the same was 72% in newborns who were at risk of developing sepsis by septicemia scoring, showing a significantly higher incidence of vertical transmission and subsequent sepsis in high risk newborns.

Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

PubMed Central

Parente-Rocha, Juliana Alves; Bailão, Alexandre Melo; Amaral, André Correa; Paccez, Juliano Domiraci; Borges, Clayton Luiz

2017-01-01

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs. PMID:28694566

Skin problems after a tsunami.

PubMed

Lee, S H; Choi, C P; Eun, H C; Kwon, O S

2006-08-01

On December 26, 2004, the biggest earthquake for 40 years, measuring 9.0 on the Richter scale, triggered a tsunami that pounded the coastal areas of South Asia and East Africa. The effects of the tsunami on skin conditions have not been evaluated. To determine the influence of the tsunami on skin conditions by evaluating the skin problems of patients presenting at hospitals after the tsunami. Between 5 and 25 January 2005, two dermatologists evaluated patients who complained of skin problems at an outpatient clinic and emergency room of a general hospital in Banda Aceh, Aceh Province, Indonesia. The total number of patients that presented during the study period was 235 (131 males and 104 females), and they had a total of 265 skin problems. In terms of age distribution, most subjects were in their fourth decade (23.0%), followed by the third (22.6%) and fifth decade (16.6%). The most prevalent skin problems were infections-infestations (32.5%), followed by eczemas (29.8%) and traumatic skin disorders (29.4%). In males, traumatic skin disorders were most common. The great majority of infection-infestation cases involved superficial fungal infections. Contact dermatitis accounted for three-quarters of eczema cases, and mainly involved the arms (40.0%) and legs (27.1%). The majority of traumatic skin disorders were lacerations, punctures and penetrations, and the feet (44.7%) and hands (18.8%) were most frequently affected. Unhygienic conditions, exposure to a hazardous environment and contact with various objects during and after the tsunami probably increased the prevalence of infections-infestations, traumatic skin disorders and contact dermatitis. To prevent these problems and associated secondary bacterial infections, health-related education and early medical management are required.

Environment, host, and fungal traits predict continental-scale white-nose syndrome in bats

USGS Publications Warehouse

Hayman, David T.S.; Pulliam, Juliet R.C.; Marshall, Jonathan C.; Cryan, Paul M.; Webb, Colleen T.

2016-01-01

White-nose syndrome is a fungal disease killing bats in eastern North America, but disease is not seen in European bats and is less severe in some North American species. We show that how bats use energy during hibernation and fungal growth rates under different environmental conditions can explain how some bats are able to survive winter with infection and others are not. Our study shows how simple but nonlinear interactions between fungal growth and bat energetics result in decreased survival times at more humid hibernation sites; however, differences between species such as body size and metabolic rates determine the impact of fungal infection on bat survival, allowing European bat species to survive, whereas North American species can experience dramatic decline.

Environment, host, and fungal traits predict continental-scale white-nose syndrome in bats.

PubMed

Hayman, David T S; Pulliam, Juliet R C; Marshall, Jonathan C; Cryan, Paul M; Webb, Colleen T

2016-01-01

White-nose syndrome is a fungal disease killing bats in eastern North America, but disease is not seen in European bats and is less severe in some North American species. We show that how bats use energy during hibernation and fungal growth rates under different environmental conditions can explain how some bats are able to survive winter with infection and others are not. Our study shows how simple but nonlinear interactions between fungal growth and bat energetics result in decreased survival times at more humid hibernation sites; however, differences between species such as body size and metabolic rates determine the impact of fungal infection on bat survival, allowing European bat species to survive, whereas North American species can experience dramatic decline.

A double-stranded RNA mycovirus confers hypovirulence-associated traits to Botrytis cinerea.

PubMed

Castro, Miguel; Kramer, Kurt; Valdivia, Lorena; Ortiz, Sylvia; Castillo, Antonio

2003-11-07

Botrytis cinerea CCg425 contains a 33-nm isometric mycovirus whose genome is a 6.8-kb double-stranded RNA (dsRNA) molecule. Virulence bioassays, performed by direct plug mycelial inoculation on bean plant leaves, showed that B. cinerea CCg425 displays less fungal aggressivity than B. cinerea CKg54, a virulent fungal strain that is not infected by dsRNA mycoviruses. B. cinerea CCg425 also showed lower laccase activity and conidiation rate than B. cinerea CKg54. Furthermore, infection of B. cinerea CKg54 with viral particles purified from B. cinerea CCg425 resulted in diminished virulence of the infected fungus. Collectively, our results indicate that mycovirus infection confers hypovirulence to the fungal host.

Support of the Laboratory in the Diagnosis of Fungal Ocular Infections

PubMed Central

Vanzzini Zago, Virginia; Alcantara Castro, Marino; Naranjo Tackman, Ramon

2012-01-01

This is a retrospective, and descriptive study about the support that the laboratory of microbiology aids can provide in the diagnosis of ocular infections in patients whom were attended a tertiary-care hospital in México City in a 10-year-time period. We describe the microbiological diagnosis in palpebral mycose; in keratitis caused by Fusarium, Aspergillus, Candida, and melanized fungi; endophthalmitis; one Histoplasma scleritis and one mucormycosis. Nowadays, ocular fungal infections are more often diagnosed, because there is more clinical suspicion and there are easy laboratory confirmations. Correct diagnosis is important because an early medical treatment gives a better prognosis for visual acuity. In some cases, fungal infections are misdiagnosed and the antifungal treatment is delayed. PMID:22518339

Insect pathogenic fungus interacts with the gut microbiota to accelerate mosquito mortality

PubMed Central

Wei, Ge; Lai, Yiling; Wang, Guandong; Chen, Huan; Li, Fang

2017-01-01

The insect gut microbiota plays crucial roles in modulating the interactions between the host and intestinal pathogens. Unlike viruses, bacteria, and parasites, which need to be ingested to cause disease, entomopathogenic fungi infect insects through the cuticle and proliferate in the hemolymph. However, interactions between the gut microbiota and entomopathogenic fungi are unknown. Here we show that the pathogenic fungus Beauveria bassiana interacts with the gut microbiota to accelerate mosquito death. After topical fungal infection, mosquitoes with gut microbiota die significantly faster than mosquitoes without microbiota. Furthermore, fungal infection causes dysbiosis of mosquito gut microbiota with a significant increase in gut bacterial load and a significant decrease in bacterial diversity. In particular, the opportunistic pathogenic bacterium Serratia marcescens overgrows in the midgut and translocates to the hemocoel, which promotes fungal killing of mosquitoes. We further reveal that fungal infection down-regulates antimicrobial peptide and dual oxidase expression in the midgut. Duox down-regulation in the midgut is mediated by secretion of the toxin oosporein from B. bassiana. Our findings reveal the important contribution of the gut microbiota in B. bassiana-killing activity, providing new insights into the mechanisms of fungal pathogenesis in insects. PMID:28533370

White-nose syndrome without borders: Pseudogymnoascus destructans infection tolerated in Europe and Palearctic Asia but not in North America.

PubMed

Zukal, Jan; Bandouchova, Hana; Brichta, Jiri; Cmokova, Adela; Jaron, Kamil S; Kolarik, Miroslav; Kovacova, Veronika; Kubátová, Alena; Nováková, Alena; Orlov, Oleg; Pikula, Jiri; Presetnik, Primož; Šuba, Jurģis; Zahradníková, Alexandra; Martínková, Natália

2016-01-29

A striking feature of white-nose syndrome, a fungal infection of hibernating bats, is the difference in infection outcome between North America and Europe. Here we show high WNS prevalence both in Europe and on the West Siberian Plain in Asia. Palearctic bat communities tolerate similar fungal loads of Pseudogymnoascus destructans infection as their Nearctic counterparts and histopathology indicates equal focal skin tissue invasiveness pathognomonic for WNS lesions. Fungal load positively correlates with disease intensity and it reaches highest values at intermediate latitudes. Prevalence and fungal load dynamics in Palearctic bats remained persistent and high between 2012 and 2014. Dominant haplotypes of five genes are widespread in North America, Europe and Asia, expanding the source region of white-nose syndrome to non-European hibernacula. Our data provides evidence for both endemicity and tolerance to this persistent virulent fungus in the Palearctic, suggesting that host-pathogen interaction equilibrium has been established.

White-nose syndrome without borders: Pseudogymnoascus destructans infection tolerated in Europe and Palearctic Asia but not in North America

PubMed Central

Zukal, Jan; Bandouchova, Hana; Brichta, Jiri; Cmokova, Adela; Jaron, Kamil S.; Kolarik, Miroslav; Kovacova, Veronika; Kubátová, Alena; Nováková, Alena; Orlov, Oleg; Pikula, Jiri; Presetnik, Primož; Šuba, Jurģis; Zahradníková Jr., Alexandra; Martínková, Natália

2016-01-01

A striking feature of white-nose syndrome, a fungal infection of hibernating bats, is the difference in infection outcome between North America and Europe. Here we show high WNS prevalence both in Europe and on the West Siberian Plain in Asia. Palearctic bat communities tolerate similar fungal loads of Pseudogymnoascus destructans infection as their Nearctic counterparts and histopathology indicates equal focal skin tissue invasiveness pathognomonic for WNS lesions. Fungal load positively correlates with disease intensity and it reaches highest values at intermediate latitudes. Prevalence and fungal load dynamics in Palearctic bats remained persistent and high between 2012 and 2014. Dominant haplotypes of five genes are widespread in North America, Europe and Asia, expanding the source region of white-nose syndrome to non-European hibernacula. Our data provides evidence for both endemicity and tolerance to this persistent virulent fungus in the Palearctic, suggesting that host-pathogen interaction equilibrium has been established. PMID:26821755

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives▿

PubMed Central

Burger-Kentischer, Anke; Finkelmeier, Doris; Keller, Petra; Bauer, Jörg; Eickhoff, Holger; Kleymann, Gerald; Abu Rayyan, Walid; Singh, Anurag; Schröppel, Klaus; Lemuth, Karin; Wiesmüller, Karl-Heinz; Rupp, Steffen

2011-01-01

Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (S)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic Candida yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules. PMID:21746957

Pathology of fungal infections of the central nervous system: 17 years' experience from Southern India.

PubMed

Sundaram, C; Umabala, P; Laxmi, V; Purohit, A K; Prasad, V S S V; Panigrahi, M; Sahu, B P; Sarathi, M V; Kaul, S; Borghain, R; Meena, A K; Jayalakshmi, S S; Suvarna, A; Mohandas, S; Murthy, J M K

2006-10-01

To describe the pathology of central nervous system (CNS) fungal infections with particular reference to India. This was a retrospective study from 1988 to 2004 constituting 130 cases. The diagnosis was based on morphology of biopsy/autopsy material. These included aspergillosis (n=73), zygomycosis (n=40), cryptococcosis (n=2), rhodotorulosis (n=1), candidiasis (n=5), maduramycosis (n=1), pheohyphomycosis (n=3) and mixed infections (n=5). Predisposing risk factors were present in 49 (38%) patients only. The majority of the patients were immunocompetent. The commonest risk factor was diabetes mellitus, the commonest route of infection was from a contiguous site and the commonest pathology was granuloma. Culture positivity was seen in only 31%. Environmental factors in tropical countries such as India play a significant role in the pathogenesis of CNS fungal infections.

Fungal Infections of the Spine.

PubMed

Ganesh, Devin; Gottlieb, Jonathan; Chan, Sherilynn; Martinez, Octavio; Eismont, Frank

2015-06-15

Review of the literature. To retrospectively examine the frequency of published fungal infections by species and the treatment algorithms used to eradicate the disease. Fungal infections of the spine present unique challenges to the modern multispecialty treatment team. Although rare in comparison with bacterial infections, fungal infections have been increasing in incidence over the past several decades. Evidences-based practice is limited to referencing smaller case series. MEDLINE, Scopus, and EMBASE searches were carried out by one of the authors as well as by the research desk at the University of Miami/Calder Memorial Library. We included peer-reviewed articles published between 1948 and September 2010; case reports, series, and reviews were all examined and compiled into a database. A total of 130 articles, representing 157 cases, were included in the review. Aspergillus (60 cases, 38.2% of the total) and Candida species (36 cases, 22.9% of the total) were the 2 most common organisms. Surgery was associated with a greater survival rate than medical management alone in patients with Aspergillus (26.9% mortality in surgical patients; 60% in medically treated patients) and Candida (0% vs. 28.6%). Overall mortality was 19.3%. The overall recurrence rate was 7.4%. Amphotericin use was associated with a higher mortality rate than azoles. Aspergillus is the most common published pathogen in fungal infections of the spine. Recent publications depicting the use of newer antifungal medications such as azoles report higher survival rates. Surgically treated patients in combination with antifungal therapy showed highest frequencies of patient survival in Aspergillus and Candida infections. 3.

Papillary necrosis with invasive fungal infections: a case series of 29 patients

PubMed Central

Gupta, Krishan L.; Muthukumar, Thangamani; Joshi, Kusum; Chakrbarti, Arunaloke; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

2013-01-01

Background Renal papillary necrosis (RPN) is associated with a number of comorbid conditions. However, it has been rarely reported in patients with fungal infections of the kidney. Methods We analyzed medical records of our hospital for the last two decades and identified 29 patients with fungal infections and RPN. Results Among the 29 patients, there were 24 men and 5 women. The median (range) age at presentation was 31.2 years (2 days–73 years). Three patients (10%) were kidney transplant recipients. The remaining had varied co-existing medical conditions that included diabetes mellitus in 16 (55%) and septicemia in 4 (14%). Clinical features at presentation were fever and oliguric kidney failure in 17 patients and loin pain accompanied by passage of fleshy material per urethra in 11 (38%). Diagnosis was made ante-mortem in 17 (59%) patients. Twenty patients (69%) had infection limited to the kidneys, while in the rest, it was disseminated. Kidney involvement was bilateral in 17 patients (59%). Urinalysis showed pyuria in 23 (79%) and microhematuria in 8 (28%) patients. Fungal infections included candidiasis (69%), aspergillosis (21%) and zygomycosis (10%). Of the 17 patients in whom the diagnoses was made ante-mortem, 12 survived and 5 died. Overall mortality was observed in 48% of cases. Conclusions We herein report a series of patients with RPN associated with fungal infections of the kidney. Presentation varies from asymptomatic urinary tract infection to severe kidney failure with poor outcome. High index of suspicion is necessary to reduce the associated high mortality in these patients. PMID:27293566

Proteomics of survival structures of fungal pathogens.

PubMed

Loginov, Dmitry; Šebela, Marek

2016-09-25

Fungal pathogens are causal agents of numerous human, animal, and plant diseases. They employ various infection modes to overcome host defense systems. Infection mechanisms of different fungi have been subjected to many comprehensive studies. These investigations have been facilitated by the development of various '-omics' techniques, and proteomics has one of the leading roles in this regard. Fungal conidia and sclerotia could be considered the most important structures for pathogenesis as their germination is one of the first steps towards a host infection. They represent interesting objects for proteomic studies because of the presence of unique proteins with unexplored biotechnological potential required for pathogen viability, development and the subsequent host infection. Proteomic peculiarities of survival structures of different fungi, including those of biotechnological significance (e.g., Asperillus fumigatus, A. nidulans, Metarhizium anisopliae), in a dormant state, as well as changes in the protein production during early stages of fungal development are the subjects of the present review. We focused on biological aspects of proteomic studies of fungal survival structures rather than on an evaluation of proteomic approaches. For that reason, proteins that have been identified in this context are discussed from the point of view of their involvement in different biological processes and possible functions assigned to them. This is the first review paper summarizing recent advances in proteomics of fungal survival structures. Copyright © 2016 Elsevier B.V. All rights reserved.

TNF-α and CD8+ T Cells Mediate the Beneficial Effects of Nitric Oxide Synthase-2 Deficiency in Pulmonary Paracoccidioidomycosis

PubMed Central

Bernardino, Simone; Pina, Adriana; Felonato, Maíra; Costa, Tânia A.; Frank de Araújo, Eliseu; Feriotti, Cláudia; Bazan, Silvia Boschi; Keller, Alexandre C.; Leite, Katia R. M.; Calich, Vera L. G.

2013-01-01

Background Nitric oxide (NO), a key antimicrobial molecule, was previously shown to exert a dual role in paracoccidioidomycosis, an endemic fungal infection in Latin America. In the intravenous and peritoneal models of infection, NO production was associated with efficient fungal clearance but also with non-organized granulomatous lesions. Because paracoccidioidomycosis is a pulmonary infection, we aimed to characterize the role of NO in a pulmonary model of infection. Methodology/Principal Findings C57Bl/6 wild type (WT) and iNOS−/− mice were i.t. infected with 1×106 Paracoccidioides brasiliensis yeasts and studied at several post-infection periods. Unexpectedly, at week 2 of infection, iNOS−/− mice showed decreased pulmonary fungal burdens associated with an M2-like macrophage profile, which expressed high levels of TGF-β impaired ability of ingesting fungal cells. This early decreased fungal loads were concomitant with increased DTH reactions, enhanced TNF-α synthesis and intense migration of activated macrophages, CD4+ and CD8+ T cells into the lungs. By week 10, iNOS−/− mice showed increased fungal burdens circumscribed, however, by compact granulomas containing elevated numbers of activated CD4+ T cells. Importantly, the enhanced immunological reactivity of iNOS−/− mice resulted in decreased mortality rates. In both mouse strains, depletion of TNF-α led to non-organized lesions and excessive influx of inflammatory cells into the lungs, but only the iNOS−/− mice showed increased mortality rates. In addition, depletion of CD8+ cells abolished the increased migration of inflammatory cells and decreased the number of TNF-α and IFN-γ CD4+ and CD8+ T cells into the lungs of iNOS−/− mice. Conclusions/Significance Our study demonstrated that NO plays a deleterious role in pulmonary paracoccidioidomycosis due to its suppressive action on TNF-α production, T cell immunity and organization of lesions resulting in precocious mortality of mice. It was also revealed that uncontrolled fungal growth can be overcome by an efficient immune response. PMID:23936574

Reducing fungal infections and testing tag loss in juvenile Pacific lampreys implanted with passive integrated transponders.

USGS Publications Warehouse

Christiansen, H.E.; Gee, L.P.; Mesa, M.G.

2012-01-01

Pacific lamprey Entosphenus tridentatus are facing severe population declines, yet little is known about juvenile lamprey passage, life history, or adult return rates because until now, these small fish could not be tagged for unique identification of live individuals. Previously, we developed a simple and effective method for tagging juvenile lampreys with passive integrated transponder (PIT) tags and showed that tagging per se did not affect survival. Mortality in tagged and untagged control fish, however, was frequently associated with fungal infection. In this study, we addressed two outstanding issues related to handling and tagging juvenile lampreys. First, we tried to mitigate freshwater fungal infections by reducing irritation and stress from anesthesia and by treating tagged fish briefly with a prophylactic immediately after tagging. We tested four anesthetics at three concentrations each and determined that 100 mg/L MS-222 and 60 mg/L BENZOAK® (benzocaine) were the most effective for anesthetizing juvenile lampreys to handleable while minimizing irritation. We also showed that fish anesthetized with BENZOAK® may have lower rates of fungal infection than those anesthetized with MS-222 or AQUI-S® 20E (eugenol). When fish anesthetized with MS-222 or BENZOAK® were given a 30 min prophylactic treatment with Stress Coat®, hydrogen peroxide, or salt immediately after tagging, few fish presented with fungal infections. However, untreated, tagged control fish also showed few fungal infections, making it difficult to determine if the prophylactic treatments were successful. The second question we addressed was whether activity would increase tag loss in PIT-tagged lampreys. We found that active swimming did not cause tag loss if fish were first held for 20–24 h after tagging. Therefore, we recommend anesthesia with MS-222 or BENZOAK® and then tagging with a 20–24 h recovery period followed by immediate release. If field studies show that lampreys are not reaching salt water (where fungal infections are mitigated) within 1–2 weeks after release, further study of prophylactic treatments may be warranted.

Jávea consensus guidelines for the treatment of Candida peritonitis and other intra-abdominal fungal infections in non-neutropenic critically ill adult patients.

PubMed

Pemán, Javier; Aguilar, Gerardo; Valía, Juan Carlos; Salavert, Miguel; Navarro, David; Zaragoza, Rafael

Although the management of the invasive candidiasis has improved in the last decade, controversial issues yet remain, especially in the diagnostic and therapeutic approaches to Candida peritonitis and other forms of intra-abdominal fungal infections. We sought to identify core clinical knowledge about intra-abdominal fungal infections and to achieve high-agreement recommendations required to care for critically ill adult patients with Candida peritonitis and other forms of intra-abdominal fungal infection. A biregional Spanish survey, to elucidate the consensus about the already mentioned fungal infections by means of the Delphi technique, was conducted anonymously by e-mail with 29 multidisciplinary experts in invasive fungal infections from 14 hospitals in the Valencia and Murcia communities during 2014. Respondents included intensivists, anesthesiologists, microbiologists, pharmacologists, and infectious disease specialists, who answered 31 questions prepared by a coordination group after a strict review of the literature from the 5 previous years. The educational objectives spanned 6 categories: epidemiology, microbiological diagnosis, clinical diagnosis, antifungal treatment, de-escalation therapy, and special situations. The agreement required among the panelists for each item to be selected had to be higher than 70%. After extracting the recommendations from the selected items, a meeting at which the experts were asked to validate the previously selected recommendations in a second round of scoring took place. After the second round, 36 recommendations were validated according to the following distribution: epidemiology (5), microbiological diagnosis (4), clinical diagnosis (4), antifungal treatment (3), de-escalation therapy (4), and special situations (16). Treatment of Candida peritonitis and other forms of intra-abdominal fungal infections in ICU patients requires a broad range of knowledge application and skills that our recommendations address. Based on the DELPHI methodology, these recommendations might help to optimize the therapeutic management of these patients in special situations and in various scenarios to improve their outcome. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Ultraviolet-C Light for Treatment of Candida albicans Burn Infection in Mice

PubMed Central

Dai, Tianhong; Kharkwal, Gitika B; Zhao, Jie; St. Denis, Tyler G; Wu, Qiuhe; Xia, Yumin; Huang, Liyi; Sharma, Sulbha K; d’Enfert, Christophe; Hamblin, Michael R

2011-01-01

Burn patients are at high risk of invasive fungal infections, which are a leading cause of morbidity, mortality, and related expense exacerbated by the emergence of drug resistant fungal strains. In this study, we investigated the use of UVC light (254-nm) for the treatment of Candida albicans infection in mouse third degree burns. In-vitro studies demonstrated that UVC could selectively kill the pathogenic yeast C. albicans compared to a normal keratinocyte cell line in a light exposure dependent manner. A mouse model of chronic C. albicans infection in non-lethal 3rd degree burns was developed. The C. albicans strain was stably transformed with a version of the Gaussia princeps luciferase gene that allowed real-time bioluminescence imaging of the progression of C. albicans infection. UVC treatment with a single exposure carried out on day 0 (30 minutes post-infection) gave an average 2.16-log10-unit (99.2%) loss of fungal luminescence when 2.92 J/cm2 UVC had been delivered, while UVC 24-hours post-infection gave 1.94-log10-unit (95.8%) reduction of fungal luminescence after 6.48 J/cm2. Statistical analysis demonstrated that UVC treatment carried out both on both day 0 and day 1 significantly reduced the fungal bioburden of infected burns. UVC was found to be superior to a topical antifungal drug, nystatin cream. UVC was tested on normal mouse skin and no gross damage was observed 24 hours after 6.48 J/cm2. DNA lesions (cyclobutane pyrimidine dimers) were observed by immunofluorescence in normal mouse skin immediately after a 6.48 J/cm2 UVC exposure, but the lesions were extensively repaired at 24-hours after UVC exposure. PMID:21208209

Fungal DNA virus infects a mycophagous insect and utilizes it as a transmission vector

PubMed Central

Liu, Si; Xie, Jiatao; Cheng, Jiasen; Li, Bo; Chen, Tao; Fu, Yanping; Li, Guoqing; Wang, Manqun; Jin, Huanan; Wan, Hu; Jiang, Daohong

2016-01-01

Mycoviruses are usually transmitted horizontally via hyphal anastomosis and vertically via sexual/asexual spores. Previously, we reported that a gemycircularvirus, Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1 (SsHADV-1), could infect its fungal host extracellularly. Here, we discovered that SsHADV-1 could infect a mycophagous insect, Lycoriella ingenua, and use it as a transmission vector. Virus acquired by larvae feeding on colonies of a virus-infected strain of S. sclerotiorum was replicated and retained in larvae, pupae, adults, and eggs. Virus could be transmitted to insect offspring when larvae were injected with virus particles and allowed to feed on a nonhost fungus. Virus replication in insect cells was further confirmed by inoculating Spodoptera frugiperda cells with virus particles and analyzing with RT-PCR, Northern blot, immunofluorescence, and flow cytometry assays. Larvae could transmit virus once they acquired virus by feeding on virus-infected fungal colony. Offspring larvae hatched from viruliferous eggs were virus carriers and could also successfully transmit virus. Virus transmission between insect and fungus also occurred on rapeseed plants. Virus-infected isolates produced less repellent volatile substances to attract adults of L. ingenua. Furthermore, L. ingenua was easily observed on Sclerotinia lesions in rapeseed fields, and viruliferous adults were captured from fields either sprayed with a virus-infected fungal strain or nonsprayed. Our findings may facilitate the exploration of mycoviruses for control of fungal diseases and enhance our understanding of the ecology of SsHADV-1 and other newly emerging SsHADV-1–like viruses, which were recently found to be widespread in various niches including human HIV-infected blood, human and animal feces, insects, plants, and even sewage. PMID:27791095

A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts.

PubMed

Gerwien, Franziska; Safyan, Abu; Wisgott, Stephanie; Hille, Fabrice; Kaemmer, Philipp; Linde, Jörg; Brunke, Sascha; Kasper, Lydia; Hube, Bernhard

2016-10-18

Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism Saccharomyces cerevisiae, which employs an evolutionarily derived system. Here, we show that C. glabrata uses a regulation network largely consisting of components of the S. cerevisiae regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker's yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with S. cerevisiae, a Sef1 ortholog is required for full growth under iron limitation conditions, making C. glabrata an evolutionary intermediate to SEF1-dependent fungal pathogens. Therefore, C. glabrata has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi. The fungus Candida glabrata represents an evolutionarily close relative of the well-studied and benign baker's yeast and model organism Saccharomyces cerevisiae On the other hand, C. glabrata is an important opportunistic human pathogen causing both superficial and systemic infections. The ability to acquire trace metals, in particular, iron, and to tightly regulate this process during infection is considered an important virulence attribute of a variety of pathogens. Importantly, S. cerevisiae uses a highly derivative regulatory system distinct from those of other fungi. Until now, the regulatory mechanism of iron homeostasis in C. glabrata has been mostly unknown. Our study revealed a hybrid iron regulation network that is unique to C. glabrata and is placed at an evolutionary midpoint between those of S. cerevisiae and related fungal pathogens. We thereby show that, in the host, even a successful human pathogen can rely largely on a strategy normally found in nonpathogenic fungi from a terrestrial environment. Copyright © 2016 Gerwien et al.

Thermal behaviour of Anopheles stephensi in response to infection with malaria and fungal entomopathogens

PubMed Central

Blanford, Simon; Read, Andrew F; Thomas, Matthew B

2009-01-01

Background Temperature is a critical determinant of the development of malaria parasites in mosquitoes, and hence the geographic distribution of malaria risk, but little is known about the thermal preferences of Anopheles. A number of other insects modify their thermal behaviour in response to infection. These alterations can be beneficial for the insect or for the infectious agent. Given current interest in developing fungal biopesticides for control of mosquitoes, Anopheles stephensi were examined to test whether mosquitoes showed thermally-mediated behaviour in response to infection with fungal entomopathogens and the rodent malaria, Plasmodium yoelii. Methods Over two experiments, groups of An. stephensi were infected with one of three entomopathogenic fungi, and/or P. yoelii. Infected and uninfected mosquitoes were released on to a thermal gradient (14 – 38°C) for "snapshot" assessments of thermal preference during the first five days post-infection. Mosquito survival was monitored for eight days and, where appropriate, oocyst prevalence and intensity was assessed. Results and conclusion Both infected and uninfected An. stephensi showed a non-random distribution on the gradient, indicating some capacity to behaviourally thermoregulate. However, chosen resting temperatures were not altered by any of the infections. There is thus no evidence that thermally-mediated behaviours play a role in determining malaria prevalence or that they will influence the performance of fungal biopesticides against adult Anopheles. PMID:19379519

Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

PubMed Central

Lee, Pamela P.; Lau, Yu-Lung

2017-01-01

The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and geographical regions. PMID:28702025

Ontogenetic changes in immunity and susceptibility to fungal infection in Mormon crickets Anabrus simplex

USDA-ARS?s Scientific Manuscript database

Insects have innate immunity that may be weakened by resource allocation to growth. I measured enzymatic immunity, encapsulation response, and susceptibility to fungal infection in Mormon crickets of known age. Although the concentrations of circulating spontaneous and total phenoloxidase (PO) incr...

Optical Coherence Tomography Findings in Endogenous Fungal Chorioretinitis, Retinitis, and Endophthalmitis.

PubMed

Stephens, John D; Adam, Murtaza K; Todorich, Bohzo; Faia, Lisa J; Garg, Sunir; Dunn, James P; Mehta, Sonia

2017-11-01

To describe spectral-domain optical coherence tomography (SD-OCT) findings in eyes with endogenous fungal chorioretinitis and endophthalmitis. Retrospective, observational case series of subjects at Wills Eye Hospital and William Beaumont Hospital were identified by screening OCT billing data and cross-referencing with patient charts. Clinical and imaging data were collected for each patient and reviewed. Twelve eyes of seven consecutive patients were identified, demonstrating two patterns of posterior ocular involvement: chorioretinal infiltration and superficial retinal/retinal vascular infiltration without choroidal involvement. Six of 12 eyes had follow-up imaging performed after antifungal treatment, which demonstrated decreased size of choroidal and/or retinal infiltrates. All patients with follow-up imaging had anatomic improvement by OCT of the lesions with treatment. In the future, OCT imaging may provide a method to assess therapeutic response and prognosis for visual recovery in patients with endogenous fungal ocular disease. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:894-901.]. Copyright 2017, SLACK Incorporated.

Estimating the Burden of Serious Fungal Infections in Uruguay

PubMed Central

Macedo-Viñas, Marina

2018-01-01

We aimed to estimate for the first time the burden of fungal infections in Uruguay. Data on population characteristics and underlying conditions were extracted from the National Statistics Institute, the World Bank, national registries, and published articles. When no data existed, risk populations were used to estimate frequencies extrapolating from the literature. Population structure (inhabitants): total 3,444,006; 73% adults; 35% women younger than 50 years. Size of populations at risk (total cases per year): HIV infected 12,000; acute myeloid leukemia 126; hematopoietic stem cell transplantation 30; solid organ transplants 134; COPD 272,006; asthma in adults 223,431; cystic fibrosis in adults 48; tuberculosis 613; lung cancer 1400. Annual incidence estimations per 100,000: invasive aspergillosis, 22.4; candidemia, 16.4; Candida peritonitis, 3.7; Pneumocystis jirovecii pneumonia, 1.62; cryptococcosis, 0.75; severe asthma with fungal sensitization, 217; allergic bronchopulmonary aspergillosis, 165; recurrent Candida vaginitis, 6323; oral candidiasis, 74.5; and esophageal candidiasis, 25.7. Although some under and overestimations could have been made, we expect that at least 127,525 people suffer from serious fungal infections each year. Sporothrichosis, histoplasmosis, paracoccidioidomycosis, and dermatophytosis are known to be frequent but no data are available to make accurate estimations. Given the magnitude of the burden of fungal infections in Uruguay, efforts should be made to improve surveillance, strengthen laboratory diagnosis, and warrant access to first line antifungals. PMID:29562641

Identification of Putative Coffee Rust Mycoparasites via Single-Molecule DNA Sequencing of Infected Pustules.

PubMed

James, Timothy Y; Marino, John A; Perfecto, Ivette; Vandermeer, John

2016-01-15

The interaction of crop pests with their natural enemies is a fundament to their control. Natural enemies of fungal pathogens of crops are poorly known relative to those of insect pests, despite the diversity of fungal pathogens and their economic importance. Currently, many regions across Latin America are experiencing unprecedented epidemics of coffee rust (Hemileia vastatrix). Identification of natural enemies of coffee rust could aid in developing management strategies or in pinpointing species that could be used for biocontrol. In the present study, we characterized fungal communities associated with coffee rust lesions by single-molecule DNA sequencing of fungal rRNA gene bar codes from leaf discs (≈28 mm(2)) containing rust lesions and control discs with no rust lesions. The leaf disc communities were hyperdiverse in terms of fungi, with up to 69 operational taxonomic units (putative species) per control disc, and the diversity was only slightly reduced in rust-infected discs, with up to 63 putative species. However, geography had a greater influence on the fungal community than whether the disc was infected by coffee rust. Through comparisons between control and rust-infected leaf discs, as well as taxonomic criteria, we identified 15 putative mycoparasitic fungi. These fungi are concentrated in the fungal family Cordycipitaceae and the order Tremellales. These data emphasize the complexity of diverse fungi of unknown ecological function within a leaf that might influence plant disease epidemics or lead to the development of species for biocontrol of fungal disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Interface between Fungal Biofilms and Innate Immunity.

PubMed

Kernien, John F; Snarr, Brendan D; Sheppard, Donald C; Nett, Jeniel E

2017-01-01

Fungal biofilms are communities of adherent cells surrounded by an extracellular matrix. These biofilms are commonly found during infection caused by a variety of fungal pathogens. Clinically, biofilm infections can be extremely difficult to eradicate due to their resistance to antifungals and host defenses. Biofilm formation can protect fungal pathogens from many aspects of the innate immune system, including killing by neutrophils and monocytes. Altered immune recognition during this phase of growth is also evident by changes in the cytokine profiles of monocytes and macrophages exposed to biofilm. In this manuscript, we review the host response to fungal biofilms, focusing on how these structures are recognized by the innate immune system. Biofilms formed by Candida, Aspergillus , and Cryptococcus have received the most attention and are highlighted. We describe common themes involved in the resilience of fungal biofilms to host immunity and give examples of biofilm defenses that are pathogen-specific.

Metabolism in Fungal Pathogenesis

PubMed Central

Ene, Iuliana V.; Brunke, Sascha; Brown, Alistair J.P.; Hube, Bernhard

2014-01-01

Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host–fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. PMID:25190251

Impact of pretransplant rifaximin therapy on early post-liver transplant infections.

PubMed

Esfeh, Jamak Modaresi; Hanouneh, Ibrahim A; Koval, Christine E; Kovacs, Christopher; Dalal, Deepan S; Ansari-Gilani, Kianoush; Confer, Bradley D; Eghtesad, Bijan; Zein, Nizar N; Menon, K V Narayanan

2014-05-01

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. © 2014 American Association for the Study of Liver Diseases.

Fungal Biofilms, Drug Resistance, and Recurrent Infection

PubMed Central

Desai, Jigar V.; Mitchell, Aaron P.; Andes, David R.

2014-01-01

A biofilm is a surface-associated microbial community. Diverse fungi are capable of biofilm growth. The significance of this growth form for infection biology is that biofilm formation on implanted devices is a major cause of recurrent infection. Biofilms also have limited drug susceptibility, making device-associated infection extremely difficult to treat. Biofilm-like growth can occur during many kinds of infection, even when an implanted device is not present. Here we summarize the current understanding of fungal biofilm formation, its genetic control, and the basis for biofilm drug resistance. PMID:25274758

Nondestructive inspection of nuts for food quality and safety using NIRS (abstract)

USDA-ARS?s Scientific Manuscript database

Mold infection and insect infestation are significant postharvest problems for processors of nuts. Fungal disease causes direct loss of product or reduced value due to the lower-quality grade of the chest-nut lot. In most cases, fungal infection is not detectable using traditional sorting techniques...

Colored and white sectors of petunia flowers display differential resistance to insect herbivores

USDA-ARS?s Scientific Manuscript database

Insect herbivory of crops increases the probability of fungal infection in damaged tissues. Mycotoxins produced by some fungi are harmful to livestock and humans. Increasing plant resistance lowers the levels of fungal infection and mycotoxin levels. The Bt toxin successfully kills only a fractio...

Identifying differentially expressed genes in leaves of Glycine tomentella in the presence of the fungal pathogen Phakopsora pachyrhizi

USDA-ARS?s Scientific Manuscript database

Transcription profiles of Glycine tomentella genotypes having different responses to soybean rust, caused by the fungal pathogen Phakopsora pachyrhizi, were compared using suppression subtractive hybridization (SSH). Four cDNA libraries were constructed from infected and non-infected leaves of resis...

Infrared spectroscopy detection of fungal infections and mycotoxins for food safety concerns

USDA-ARS?s Scientific Manuscript database

Mycotoxins, which are toxins produced by fungi, can pose great danger to human health with their acute and chronic effects when contaminated foods (grains, fruits, meat, or milk) are ingested. Fungal infections in food crops are extremely common and many developed countries have set standards to mon...

Sporotrichosis outbreak and mouldy 
hay in NSW.

PubMed

Dhingra, Deeksha; Durrheim, David; Porigneaux, Philippe

2015-04-01

Sporotrichosis is a subacute/chronic fungal infection caused by Sporothrix schenckii. The fungus thrives on organic matter including hay, wood, moss, soil and plants. Zoonotic transmission has also been reported. Lesions present as superficial skin nodules that become purulent and ulcerate. Lymphocutaneous spread is common. Haematogenous spread is uncommon and case fatality is rare. The aim of this article is to describe an outbreak of sporotrichosis in New South Wales. A cluster of six cases was identified in the NSW mid-north coast area in the first half of 2013. Telephone interviews were conducted in an attempt to identify possible exposures. General practitioners were contacted to report on patients with chronic non-healing skin lesions. A batch of mouldy hay supplied by a local farmer was identified as the potential source of exposure. Despite effective treatment with oral antifungals, diagnosis of sporotrichosis is often delayed and prolonged courses of antibiotics are unnecessarily prescribed. Timely detection and management (including referral to a dermatologist or infectious diseases specialist) significantly reduces morbidity. Personal protection is the key to prevention.

Antifungal Wound Penetration of Amphotericin and Voriconazole in Combat-related Injuries: Case Report

DTIC Science & Technology

2015-04-15

trauma can have long and challenging recoveries , which may be complicated by infection. Invasive fungal infections are a rare but serious complication...and massive blood transfu- sion [6]. Inoculation of soil-dwelling molds into wounds is proposed to occur at the time of injury, with subsequent growth...microbiological assays in austere field hos- pitals, histopathological confirmation, and positive fungal culture. Thus, the median time from infection

Single-stage revision for fungal peri-prosthetic joint infection: a single-centre experience.

PubMed

Klatte, T O; Kendoff, D; Kamath, A F; Jonen, V; Rueger, J M; Frommelt, L; Gebauer, M; Gehrke, T

2014-04-01

Fungal peri-prosthetic infections of the knee and hip are rare but likely to result in devastating complications. In this study we evaluated the results of their management using a single-stage exchange technique. Between 2001 and 2011, 14 patients (ten hips, four knees) were treated for a peri-prosthetic fungal infection. One patient was excluded because revision surgery was not possible owing to a large acetabular defect. One patient developed a further infection two months post-operatively and was excluded from the analysis. Two patients died of unrelated causes. After a mean of seven years (3 to 11) a total of ten patients were available for follow-up. One patient, undergoing revision replacement of the hip, had a post-operative dislocation. Another patient, undergoing revision replacement of the knee, developed a wound infection and required revision 29 months post-operatively following a peri-prosthetic femoral fracture. The mean Harris hip score increased to 74 points (63 to 84; p < 0.02) in those undergoing revision replacement of the hip, and the mean Hospital for Special Surgery knee score increased to 75 points (70 to 80; p < 0.01) in those undergoing revision replacement of the knee. A single-stage revision following fungal peri-prosthetic infection is feasible, with an acceptable rate of a satisfactory outcome.

[Mixed invasive fungal infection due to Rhizomucor pusillus and Aspergillus niger in an immunocompetent patient].

PubMed

Pozo-Laderas, Juan Carlos; Pontes-Moreno, Antonio; Robles-Arista, Juan Carlos; Bautista-Rodriguez, M Dolores; Candau-Alvarez, Alberto; Caro-Cuenca, Maria Teresa; Linares-Sicilia, María José

2015-01-01

Mucormycosis infections are rare in immunocompetent patients, and very few cases of mucormycosis associated with aspergillosis in non-haematological patients have been reported. A 17-year-old male, immunocompetent and without any previously known risk factors, was admitted to hospital due to a seizure episode 11 days after a motorcycle accident. He had a complicated clinical course as he had a mixed invasive fungal infection with pulmonary involvement due to Aspergillus niger and disseminated mucormycosis due to Rhizomucor pusillus (histopathological and microbiological diagnosis in several non-contiguous sites). He was treated with liposomal amphotericin B for 7 weeks (total cumulative dose >10 g) and required several surgical operations. The patient survived and was discharged from ICU after 5 months and multiple complications. Treatment with liposomal amphotericin B and aggressive surgical management achieved the eradication of a mixed invasive fungal infection. However, we emphasise the need to maintain a higher level of clinical suspicion and to perform microbiological techniques for early diagnosis of invasive fungal infections in non-immunocompromised patients, in order to prevent spread of the disease and the poor prognosis associated with it. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Snake fungal disease: an emerging threat to wild snakes.

PubMed

Lorch, Jeffrey M; Knowles, Susan; Lankton, Julia S; Michell, Kathy; Edwards, Jaime L; Kapfer, Joshua M; Staffen, Richard A; Wild, Erik R; Schmidt, Katie Z; Ballmann, Anne E; Blodgett, Doug; Farrell, Terence M; Glorioso, Brad M; Last, Lisa A; Price, Steven J; Schuler, Krysten L; Smith, Christopher E; Wellehan, James F X; Blehert, David S

2016-12-05

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Author(s).

Snake fungal disease: an emerging threat to wild snakes

PubMed Central

Lorch, Jeffrey M.; Knowles, Susan; Lankton, Julia S.; Michell, Kathy; Edwards, Jaime L.; Kapfer, Joshua M.; Staffen, Richard A.; Wild, Erik R.; Schmidt, Katie Z.; Ballmann, Anne E.; Blodgett, Doug; Farrell, Terence M.; Glorioso, Brad M.; Last, Lisa A.; Price, Steven J.; Schuler, Krysten L.; Smith, Christopher E.; Wellehan, James F. X.; Blehert, David S.

2016-01-01

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080983

Yeast infection in a beached southern right whale (Eubalaena australis) neonate.

PubMed

Mouton, Marnel; Reeb, Desray; Botha, Alfred; Best, Peter

2009-07-01

A female southern right whale (Eubalaena australis) neonate was found stranded on the Western Cape coast of southern Africa. Skin samples were taken the same day from three different locations on the animal's body and stored at -20 C. Isolation through repetitive culture of these skin sections yielded a single yeast species, Candida zeylanoides. Total genomic DNA also was isolated directly from skin samples. Polymerase chain reaction analysis of the internal transcribed spacer region of the fungal ribosomal gene cluster revealed the presence of Filobasidiella neoformans var. neoformans, the teleomorphic state of Cryptococcus neoformans. Fungal infections in cetaceans seem to be limited when compared to infections caused by bacteria, viruses and parasites. However, Candida species appear to be the most common type of fungal infection associated with cetaceans. To our knowledge this is the first report of a C. zeylanoides infection in a mysticete, as well as the first report of a dual infection involving two opportunistic pathogenic yeast species in a cetacean.

Emerging infectious diseases with cutaneous manifestations: Fungal, helminthic, protozoan and ectoparasitic infections.

PubMed

Kollipara, Ramya; Peranteau, Andrew J; Nawas, Zeena Y; Tong, Yun; Woc-Colburn, Laila; Yan, Albert C; Lupi, Omar; Tyring, Stephen K

2016-07-01

Given increased international travel, immigration, changing climate conditions, and the increased incidence of iatrogenic immunosuppression, fungal, protozoan, helminthic, and ectoparasitic infections that were once uncommon are being seeing more frequently in the Western hemisphere. However, the diagnosis and management of these infections is fraught with a lack of consistency because there is a dearth of dermatology literature on the cutaneous manifestations of these infections. In addition, delays in the diagnosis and treatment of these diseases can lead to significant patient morbidity and mortality. We review the epidemiology, cutaneous manifestations, diagnostic modalities, and treatment options for emerging fungal, protozoan, helminthic, and ectoparasitic infections. It should be noted, however, that throughout this review we cite statistics documenting their increased incidence to back-up these infections as emerging, and although some of the diagnoses are clinical, others rely on newer laboratory tests, and the possibility exists that the increased incidence could be caused by better detection methods. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Invasive forms of Candida and Aspergillus in sputum samples of pulmonary tuberculosis patients attending the tuberculosis reference laboratory in Ghaemshahr, Northern Iran: An analysis of samples collected during the past 10years.

PubMed

Jabbari Amiri, Mohammad Reza; Aghili, Seyed Reza; Shokohi, Tahereh; Hedayati, Mohammad Taghi; Abastabar, Mahdi; Aliyali, Masoud; Jabbari Amiri, Masoumeh; Hasanpour, Hamid

2016-12-01

Tuberculosis (TB) continues to be a major public health problem worldwide. This is especially true in Northern Iran, which has high TB prevalence. The chronic nature of this disease is further exacerbated if it is accompanied by fungal infection, which usually remains undiagnosed and thus untreated. Thus, mycotic infections add fatal dimensions to pulmonary TB. Our objective was to determine the prevalence of invasive forms of fungal elements in sputum samples collected from patients with pulmonary TB at a reference laboratory in Ghaemshahr, Northern Iran, during the past 10years. In this retrospective study, sputum samples collected from 430 patients were examined. Pulmonary TB in patients was confirmed in our laboratory, and samples obtained during the period from March 2006 to February 2016 were analyzed. The sputum samples were subjected to biological (bacterial) staining (Ziehl-Neelsen and fluorochrome) and mycological investigation using KOH + Calcofluor White (Sigma-Aldrich, India) by fluorescent microscopy and fungal culture on Sabouraud dextrose agar (Sigma-Aldrich, India) and CHROMagar (Paris, France). Invasive forms of fungal pathogens were observed as co-infection with Mycobacterium tuberculosis in 28/430 cases (6.51%). The frequency of Aspergillus, both branching and dichotomous infection, accounted for 3.72% (16/430): Aspergillus flavus, 1.63%; Aspergillus fumigatus, 1.16%; Aspergillus niger, 0.69%; and Aspergillus oryzae, 0.23%, respectively. Blastoconidia and pseudohyphae forms of yeast were observed as co-infection with M. tuberculosis in 2.79% (12/430) of the cases: Candida albicans, 1.86%; Candida krusei, 0.46%; and other Candida species, 0.46%, respectively. Northern Iran is a critical region in the TB world and multidrug-resistant TB is a serious problem in this region. Although it is believed that there exists a commensal relationship between fungus and TB infections, the invasive forms of fungal pathogens and their co-infection can be caused by increasing disability and failure of treatment. Diagnosis of secondary or co-existing fungal infections in TB is most important for reducing the mortality and morbidity of these patients. Copyright © 2016.

Integrated genomics of Mucorales reveals novel therapeutic targets

USDA-ARS?s Scientific Manuscript database

Mucormycosis is a life-threatening infection caused by Mucorales fungi. We sequenced 30 fungal genomes and performed transcriptomics with three representative Rhizopus and Mucor strains with human airway epithelial cells during fungal invasion to reveal key host and fungal determinants contributing ...

A Model for Evaluating Topical Antimicrobial Efficacy against Methicillin-Resistant Staphylococcus aureus Biofilms in Superficial Murine Wounds

PubMed Central

Renick, Paul J.; Tetens, Shannon P.; Carson, Dennis L.

2012-01-01

A wound biofilm model was created by adapting a superficial infection model. Partial-thickness murine wounds were inoculated with methicillin-resistant Staphylococcus aureus (MRSA). Dense biofilm communities developed at the wound surface after 24 h as demonstrated by microscopy and quantitative microbiology. Common topical antimicrobial agents had reduced efficacy when treatment was initiated 24 h after inoculation compared to 4 h after inoculation. This model provides a rapid in vivo test for new agents to treat wound biofilm infections. PMID:22644024

Antifungal activity of a β-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

PubMed

Raman, Namrata; Lee, Myung-Ryul; Rodríguez López, Angélica de L; Palecek, Sean P; Lynn, David M

2016-10-01

Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of antifungal β-peptide-based mimetics of antimicrobial peptides (AMPs) to kill C. albicans and prevent biofilm formation in synthetic urine. Many α-peptide-based AMPs exhibit antifungal activities, but are unstable in high ionic strength media and are easily degraded by proteases-features that limit their use in urinary catheter applications. Here, we demonstrate that β-peptides designed to mimic the amphiphilic helical structures of AMPs retain 100% of their structural stability and exhibit antifungal and anti-biofilm activity against C. albicans in a synthetic medium that mimics the composition of urine. We demonstrate further that these agents can be loaded into and released from polymer-based multilayer coatings applied to polyurethane, polyethylene, and silicone tubing commonly used as urinary catheters. Our results reveal catheters coated with β-peptide-loaded multilayers to kill planktonic fungal cells for up to 21days of intermittent challenges with C. albicans and prevent biofilm formation on catheter walls for at least 48h. These new materials and approaches could lead to advances that reduce the occurrence of fungal CAUTI. Catheter-associated urinary tract infections are the most common type of hospital-acquired infection. The human pathogen Candida albicans is the leading cause of fungal urinary tract infections, and forms difficult to remove 'biofilms' on the surfaces of urinary catheters. We investigated synthetic β-peptide mimics of natural antimicrobial peptides as an approach to kill C. albicans and prevent biofilm formation in media that mimics the composition of urine. Our results reveal these mimics to retain structural stability and activity against C. albicans in synthetic urine. We also report polymer-based approaches to the local release of these agents within urinary catheter tubes. With further development, these materials-based approaches could lead to advances that reduce the occurrence of fungal urinary tract infections. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Fungal keratitis caused by Scedosporium apiospermum: first report from Turkey-comment].

PubMed

Atalay, Mustafa Altay; Koc, Ayşe Nedret

2014-04-01

Scedosporium apiospermum is a saprophytic fungus which is isolated worldwide in soil, fertilizers, polluted water, rotten vegetables, and other natural environments. It is the cause of mycetoma, a subcutaneous infection, characterized by granule formation. It may also cause severe local or diffuse infections in immunosuppressive patients. S.apiospermum-induced arthritis, endocarditis, keratitis, scleritis, endophthalmitis, meningitis, osteomyelitis, otomycosis, onychomycosis, chronic prostatitis, peritonitis, esophagitis, renal infection, and hepatosplenic abscess have been previously reported in the literature. Possible risk factors of fungal keratitis, one of the major causes of fungal ocular infection, include ocular injury, long-term therapy with topical or systemic steroids, immunosuppressive agents, and underlying diseases such as pre-existing corneal surface abnormality and diabetes mellitus, and wearing contact lenses. We paid great attention to the case report presented by Kalkan Akçay E et al. titled "Fungal keratitis caused by Scedosporium apiospermum: first report from Turkey", which was published in the October 2013 issue of Bulletin of Microbiology [Mikrobiyol Bul 2013; 47(4): 727-33]. Although it is deemed as the first case report of S.apiospermum-related fungal keratitis in Turkey, there were several previous case reports of ocular infections associated with this type of fungus in Turkey, including those of Yucel A titled "An eye mycosis caused by Scedosporium apiospermum (Monosporium apiospermum)" published in 1989, Kiratli et al. titled "Scedosporium apiospermum chorioretinitis" in 2001, Saracli et al. titled "Scedosporium apiospermum keratitis treated with itraconazole" in 2003 and Erdem et al. titled "Clinical follow up of a keratomycosis case with total corneal melting" in 2005. In conclusion, it should be highlighted that the report of Kalkan Akcay et al. is not the first case report of Scedosporium apiospermum-related fungal keratitis in Turkey. We believe, hence, that correction of this misinformation would be beneficial for further studies.

Natural Killer Cells in Antifungal Immunity.

PubMed

Schmidt, Stanislaw; Tramsen, Lars; Lehrnbecher, Thomas

2017-01-01

Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high. It is therefore of major interest to improve our understanding of the host-pathogen interaction to develop new therapeutic approaches such as adoptive immunotherapy. As experimental methodologies have improved and we now better understand the complex network of the immune system, the insight in the interaction of the host with the fungus has significantly increased. It has become clear that host resistance to fungal infections is not only associated with strong innate immunity but that adaptive immunity (e.g., T cells) also plays an important role. The antifungal activity of natural killer (NK) cells has been underestimated for a long time. In vitro studies demonstrated that NK cells from murine and human origin are able to attack fungi of different genera and species. NK cells exhibit not only a direct antifungal activity via cytotoxic molecules but also an indirect antifungal activity via cytokines. However, it has been show that fungi exert immunosuppressive effects on NK cells. Whereas clinical data are scarce, animal models have clearly demonstrated that NK cells play an important role in the host response against invasive fungal infections. In this review, we summarize clinical data as well as results from in vitro and animal studies on the impact of NK cells on fungal pathogens.

Polyphenols in ceratocystis minor infected Pinus Taeda: fungal metabolites, phloem, and xylem phenols

Treesearch

R.W. Hemingway; G.W. McGraw; S.J. Barras

1977-01-01

Since Ceratocystis minor is central to the death of pines infested by southern pine beetles, changes in polyphenols of infected loblolly pine were examined with regard to accumulation of fungal metabolites and changes in concentrations of fungitoxic and fungistatic phloem and xylem constitutents. C. minor grown in liquid culture...

Polyphenols in Ceratocystis minor infected Pinus taeda: fungal metabolites, phloem and xylem phenols

Treesearch

Richard W. Hemingway; Gerald W. McGraw; Stanley J. Barras

1977-01-01

Since Ceratocystis minor is central to the death of pines infested by southern pine beetles, changes in polyphenols of infected loblolly pine were examined with regard to accumulation of fungal metabolites and changes in concentrations of fungitoxic and fungistatic phloem and xylem constitutents. C. minor grown in liquid culture...

Low-dose gamma irradiation following hot water immersion of papaya (Carica papaya linn.) fruits provides additional control of postharvest fungal infection to extend shelf life

NASA Astrophysics Data System (ADS)

Rashid, M. H. A.; Grout, B. W. W.; Continella, A.; Mahmud, T. M. M.

2015-05-01

Low-dose gamma irradiation (0.08 kGy over 10 min), a level significantly below that required to satisfy the majority of international quarantine regulations, has been employed to provide a significant reduction in visible fungal infection on papaya fruit surfaces. This is appropriate for local and national markets in producer countries where levels of commercial acceptability can be retained despite surface lesions due to fungal infection. Irradiation alone and in combination with hot-water immersion (50 °C for 10 min) has been applied to papaya (Carica papaya L.) fruits at both the mature green and 1/3 yellow stages of maturity. The incidence and severity of surface fungal infections, including anthracnose, were significantly reduced by the combined treatment compared to irradiation or hot water treatment alone, extending storage at 11 °C by 13 days and retaining commercial acceptability. The combined treatment had no significant, negative impact on ripening, with quality characteristics such as surface and internal colour change, firmness, soluble solids, acidity and vitamin C maintained at acceptable levels.

Potential of novel drug delivery systems in the management of topical candidiasis.

PubMed

Mathur, Mahima; Devi, V Kusum

2017-09-01

High prevalence of topical fungal infections is perceived in majority of nations worldwide accounting for numerous serious systemic complications. Of several fungal infections, candidiasis is one of the widespread infections which is manifested due to localisation and proliferation of fungi. Present pharmacotherapy offers an effective treatment but possesses serious limitations like inadequate solubility, ineffectiveness in lowering diseased condition and patient incompliance. Several attempts to overcome these shortcomings and building suitable technology platforms for development of appropriate dosage forms which can enhance effectiveness, patient acceptability while maintaining safety, efficacy and affordability of drug delivery, have been made. Present review highlights on different types of fungal infections, its aetiology, pathophysiology, epidemiology and conventional formulations used. It also emphasises on applications of several novel approaches of anti-fungal drugs demonstrating advantages and limitations. Details regarding patterns of drug release and its site specificity with better patient compliance have been focussed. Etiology and pathogenesis of candidiasis should be understood clearly. Mentioned novel dosage forms should be explored to enhance therapeutic efficacy, subsequently investigating marketability and patentability. Nanoparticles seem to be a promising approach befitting all requirements.

Parasites and phytoplankton, with special emphasis on dinoflagellate infections.

PubMed

Park, Myung Gil; Yih, Wonho; Coats, D Wayne

2004-01-01

Planktonic members of most algal groups are known to harbor intracellular symbionts, including viruses, bacteria, fungi, and protozoa. Among the dinoflagellates, viral and bacterial associations were recognized a quarter century ago, yet their impact on host populations remains largely unresolved. By contrast, fungal and protozoan infections of dinoflagellates are well documented and generally viewed as playing major roles in host population dynamics. Our understanding of fungal parasites is largely based on studies for freshwater diatoms and dinoflagellates, although fungal infections are known for some marine phytoplankton. In freshwater systems, fungal chytrids have been linked to mass mortalities of host organisms, suppression or retardation of phytoplankton blooms, and selective effects on species composition leading to successional changes in plankton communities. Parasitic dinoflagellates of the genus Amoebophrya and the newly described Perkinsozoa, Parvilucifera infectans, are widely distributed in coastal waters of the world where they commonly infect photosynthetic and heterotrophic dinoflagellates. Recent work indicates that these parasites can have significant impacts on host physiology, behavior, and bloom dynamics. Thus, parasitism needs to be carefully considered in developing concepts about plankton dynamics and the flow of material in marine food webs.

Snake fungal disease: An emerging threat to wild snakes

USGS Publications Warehouse

Lorch, Jeffrey M.; Knowles, Susan N.; Lankton, Julia S.; Michell, Kathy; Edwards, Jaime L.; Kapfer, Joshua M.; Staffen, Richard A.; Wild, Erik R.; Schmidt, Katie Z.; Ballmann, Anne; Blodgett, Doug; Farrell, Terence M.; Glorioso, Brad M.; Last, Lisa A.; Price, Steven J.; Schuler, Krysten L.; Smith, Christopher; Wellehan, James F. X.; Blehert, David S.

2016-01-01

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused byOphidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts.

Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.

PubMed

Hopke, Alex; Brown, Alistair J P; Hall, Rebecca A; Wheeler, Robert T

2018-04-01

Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

First genomic survey of human skin fungal diversity

Cancer.gov

Fungal infections of the skin affect 29 million people in the United States. In the first study of human fungal skin diversity, National Institutes of Health researchers sequenced the DNA of fungi that thrive at different skin sites of healthy adults to d

Proposal for a new ISHAM Working group on Clinical Fusarium

USDA-ARS?s Scientific Manuscript database

Infections caused by Fusarium species can be classified in three classes: 1) Superficial infections of skin and nails; 2) Keratitis of the cornea; and 3) Deep and disseminated infections. Whereas the first two types of these opportunistic infections are generally seen in immunocompetent hosts, the d...

Biodiversity of complexes of mycotoxigenic fungal species associated with Fusarium ear rot of maize and Aspergillus rot of grape.

PubMed

Logrieco, A; Moretti, A; Perrone, G; Mulè, G

2007-10-20

Fusarium ear rot of maize and Aspergillus rot of grape are two examples of important plant diseases caused by complexes of species of mycotoxigenic fungi. These complexes of species tend to be closely related, produce different classes of mycotoxins, and can induce disease under different environmental conditions. The infection of maize and grape with multiple fungal species and the resulting production of large classes of mycotoxins is an example of mutual aggressiveness of microorganisms toward host species as well as to humans and animals that eat feed or food derived from the infected and contaminated plants. Infection of crop plant with a complex of microbial species certainly represents a greater threat to a crop plant and to human and animal health than infection of the plant with a single fungal species.

Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies.

PubMed

Al-Bader, Nadia; Sheppard, Donald C

2016-11-16

Invasive aspergillosis is a life-threatening infection caused by the opportunistic filamentous fungus Aspergillus fumigatus. Patients undergoing haematopoietic stem cell transplant (HSCT) for the treatment of hematological malignancy are at particularly high risk of developing this fatal infection. The susceptibility of HSCT patients to infection with A. fumigatus is a consequence of a complex interplay of both fungal and host factors. Here we review our understanding of the host-pathogen interactions underlying the susceptibility of the immunocompromised host to infection with A. fumigatus with a focus on the experimental validation of fungal and host factors relevant to HSCT patients. These include fungal factors such as secondary metabolites, cell wall constituents, and metabolic adaptations that facilitate immune evasion and survival within the host microenvironment, as well as the innate and adaptive immune responses involved in host defense against A. fumigatus.

Diagnosis and management of fungal urinary tract infection.

PubMed

Kauffman, Carol A

2014-03-01

When the terms funguria or fungal urinary tract infection are used, most physicians are referring to candiduria and urinary tract infections due to Candida species. Other fungi, including yeasts and molds can involve the kidney during the course of disseminated infection, but rarely cause symptoms referable to the urinary tract. Candida species appear to be unique in their ability to both colonize and cause invasive disease in the urinary tract. This overview focuses only on candiduria and Candida urinary tract infection because they are common and many times present perplexing management issues. Published by Elsevier Inc.

Plant Phenotypic and Transcriptional Changes Induced by Volatiles from the Fungal Root Pathogen Rhizoctonia solani

PubMed Central

Cordovez, Viviane; Mommer, Liesje; Moisan, Kay; Lucas-Barbosa, Dani; Pierik, Ronald; Mumm, Roland; Carrion, Victor J.; Raaijmakers, Jos M.

2017-01-01

Beneficial soil microorganisms can affect plant growth and resistance by the production of volatile organic compounds (VOCs). Yet, little is known on how VOCs from soil-borne plant pathogens affect plant growth and resistance. Here we show that VOCs released from mycelium and sclerotia of the fungal root pathogen Rhizoctonia solani enhance growth and accelerate development of Arabidopsis thaliana. Seedlings briefly exposed to the fungal VOCs showed similar phenotypes, suggesting that enhanced biomass and accelerated development are primed already at early developmental stages. Fungal VOCs did not affect plant resistance to infection by the VOC-producing pathogen itself but reduced aboveground resistance to the herbivore Mamestra brassicae. Transcriptomics of A. thaliana revealed that genes involved in auxin signaling were up-regulated, whereas ethylene and jasmonic acid signaling pathways were down-regulated by fungal VOCs. Mutants disrupted in these pathways showed similar VOC-mediated growth responses as the wild-type A. thaliana, suggesting that other yet unknown pathways play a more prominent role. We postulate that R. solani uses VOCs to predispose plants for infection from a distance by altering root architecture and enhancing root biomass. Alternatively, plants may use enhanced root growth upon fungal VOC perception to sacrifice part of the root biomass and accelerate development and reproduction to survive infection. PMID:28785271

Iron and copper as virulence modulators in human fungal pathogens.

PubMed

Ding, Chen; Festa, Richard A; Sun, Tian-Shu; Wang, Zhan-You

2014-07-01

Fungal pathogens have evolved sophisticated machinery to precisely balance the fine line between acquiring essential metals and defending against metal toxicity. Iron and copper are essential metals for many processes in both fungal pathogens and their mammalian hosts, but reduce viability when present in excess. However, during infection, the host uses these two metals differently. Fe has a long-standing history of influencing virulence in pathogenic fungi, mostly in regards to Fe acquisition. Numerous studies demonstrate the requirement of the Fe acquisition pathway of Candida, Cryptococcus and Aspergillus for successful systemic infection. Fe is not free in the host, but is associated with Fe-binding proteins, leading fungi to develop mechanisms to interact with and to acquire Fe from these Fe-bound proteins. Cu is also essential for cell growth and development. Essential Cu-binding proteins include Fe transporters, superoxide dismutase (SOD) and cytochrome c oxidase. Although Cu acquisition plays critical roles in fungal survival in the host, recent work has revealed that Cu detoxification is extremely important. Here, we review fungal responses to altered metal conditions presented by the host, contrast the roles of Fe and Cu during infection, and outline the critical roles of fungal metal homeostasis machinery at the host-pathogen axis. © 2014 John Wiley & Sons Ltd.

Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.

PubMed

Carreto-Binaghi, Laura Elena; Aliouat, El Moukhtar; Taylor, Maria Lucia

2016-06-01

Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host's lung immune response; they act as opsonins for different pathogens via a C-terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins' regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways.

Mast Cell Activation Protects Cornea by Promoting Neutrophil Infiltration via Stimulating ICAM-1 and Vascular Dilation in Fungal Keratitis.

PubMed

Xie, Yanting; Zhang, Hongmin; Liu, Susu; Chen, Guoming; He, Siyu; Li, Zhijie; Wang, Liya

2018-05-30

The role of mast cells (MCs) in fungal infection is largely unknown. This study was to explore a protective role and mechanism of MCs in fungal keratitis. Experimental fungal keratitis (FK) mouse model was developed. Mice untreated (UT) or receiving corneal wound without fungal infection (Mock) were used as controls. Large number of connective tissue MCs was found in normal mice. MC activation with degranulation was largely observed, and the percentage of degranulated/total cells was high in FK. Dilated limbal vasculature with increased permeability, as well as largely infiltrated neutrophils with stimulated ICAM-1 protein levels were observed in corneas of FK mice, when compared with Mock and UT mice. Interestingly, pretreatment with cromolyn sodium (Block) significantly blocked MC degranulation, dramatically suppressed vascular dilation and permeability, and markedly reduced neutrophil infiltration with lower ICAM-1 levels in FK mice at 6-24 hours. Furthermore, the Block mice manifested prolonged disease course, increased pathological damage, and vigorous fungus growth, with much higher corneal perforation rate than FK mice at 72 h. These findings reveal a novel phenomenon that MCs play a vital role in protecting cornea against fungal infection through degranulation that promotes neutrophil infiltration via stimulating ICAM-1 production and limbal vascular dilation and permeability.

Subcutaneous aspergillosis with coexisting atypical mycobacterial infection.

PubMed

Duraipandian, Jeyakumari; Rengasamy, Gopal; Madasamy, Balamurugan; Kulanthaivelu, Ambedkarraj; Subramanian, Girija

2010-01-01

A 60-year-old woman, a known diabetic and asthmatic, was admitted for acute exacerbation of chronic obstructive pulmonary disease. Physical examination revealed two soft nodules in the left infra axillary region. Fine needle aspiration cytology (FNAC) showed fungal granulomatous reaction suggestive of fungal infection. Periodic acid Schiff stain (PAS stain) revealed PAS positive, acutely branching, septate fungal hyphae. Wet mount of the aspirate revealed plenty of pus cells and branching septate hyphae. Ziehl-Neelsen (ZN) stain showed moderate numbers of acid fast bacilli. Culture yielded Aspergillus flavus and Mycobacterium fortuitum.

Emerging IL-12 family cytokines in the fight against fungal infections.

PubMed

Thompson, Aiysha; Orr, Selinda J

2018-05-21

Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses. Interleukin (IL)-12 family members (IL-12p70, IL-23, IL-27 and IL-35) link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-12 and IL-23 have established roles during anti-fungal immunity, whereas emerging roles for IL-27 and IL-35 have recently been reported. Here, we discuss the IL-12 family, focusing on IL-27 and IL-35 during anti-fungal immune responses to pathogens such as Candida and Aspergillus. Copyright © 2018. Published by Elsevier Ltd.

Breast augmentation, antibiotic prophylaxis, and infection: comparative analysis of 1,628 primary augmentation mammoplasties assessing the role and efficacy of antibiotics prophylaxis duration.

PubMed

Khan, Umar Daraz

2010-02-01

Infections after augmentation mammoplasty are not uncommon, and prophylactic antibiotics are routinely administered to minimize infection. However, there is paucity of information on the relationship between the length of prophylaxis cover and its benefits in primary augmentation mammoplasty. A retrospective analysis of different antibiotic cover regimens, their effectiveness in preventing infections, and the management of infection in established cases is reviewed. A retrospective chart analysis of periprosthetic infections in primary augmentation mammoplasties performed over the past 10 years was conducted. Periprosthetic infection was determined by the presence of pain, swelling, redness, and discharge. Each breast was taken as an individual unit in 1,628 patients, and data for 3,256 breasts were analyzed. The patients had their augmentation in the partial submuscular plane (214 breasts in 107 patients), the subglandular plane (1,548 breasts in 774 patients), and the muscle-splitting biplane (1,494 breasts in 747 patients). All the patients had soft round cohesive gel silicone implants. Of the 3,256 implants, 3,218 were textured, and 38 were smooth surfaced. The patients received antibiotics as a single intravenous dose of cephalosporin (474 breasts in 237 patients), a single intravenous dose plus an oral dose for 24 h (344 breasts in 172 patients), or a single intravenous dose plus an oral course for 5 days (2,438 breasts in 1,219 patients). Infection was recorded as superficial (e.g., wound breakdown, stitch extrusion, stitch abscess) or deep (periprosthetic). The patients with established periprosthetic infections, determined clinically by the presence of pain, discharge, swelling, and redness of the breasts, were managed either conservatively using antibiotics, passive wound drainage, and healing of the wound with secondary intention or by explantation and replacement after 3 to 4 months. In selected cases of periprosthetic infection, the implants were removed after a course of antibiotics and negative swab cultures. The cavity was washed thoroughly with betadine and saline, and new implants were simultaneously reimplanted. The incidence of infection was lowest with a single perioperative dose of intravenous antibiotic compared with a combination of intravenous and oral antibiotics. Superficial infection was seen in 38 breasts (all unilateral), with an incidence of 1.2%, and periprosthetic infection was observed in 17 breasts (13 unilateral and 2 bilateral), giving an infection incidence of 0.52% (p = 0.002). In patients with a single intravenous dose of antibiotic, superficial and periprosthetic infection was seen in four breasts (0.8%) and no breasts, respectively. The difference was not significant (p = 0.13). The patients receiving a single intravenous antibiotic and a 24-h oral antibiotic had superficial and periprosthetic infection rates of 2.3% (8 breasts) and 0.3% (1 breast), respectively, and the difference between the two sub-groups was significantly higher (p = 0.04). The patients receiving an intravenous antibiotic and 5 days of oral antibiotics had superficial and periprosthetic infection rates of 1.1% (26 breasts) and 0.65% (14 breasts), respectively. The difference between the two subgroups was not significant (p = 0.09). Of the 17 periprosthetic infections in 15 patients (13 unilateral and 2 bilateral), 11 breasts (1 bilateral and 9 unilateral) were treated conservatively using antibiotics, passive drainage, and wound healing with secondary intention. Capsular contracture developed in two of the conservatively treated breasts, requiring capsulotomies with change of implants. Of the six periprosthetic infections in six patients, requiring surgical intervention, two implants were treated using explantation with immediate replacement after a course of antibiotics and a negative culture, and two implants were explanted followed by reimplantation later. One patient had both implants removed after unilateral infection, and no reimplantation was performed. One patient had a bilateral infection. In this case, one implant was explanted and the other was treated conservatively. The patient had bilateral reimplantion 6 months later, and bilateral Baker 4 capsular contracture developed in both breasts within 6 months. No other complications were seen in the patients who underwent surgery. A single dose of intravenous antibiotic is adequate for prophylaxis in breast augmentation surgery, and the extra duration of antibiotic cover does not result in reduced superficial or periprosthetic infections. Infection can be managed in more than one way depending on the nature, degree, and extent of infection.

The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System

PubMed Central

Camilli, Giorgio; Tabouret, Guillaume; Quintin, Jessica

2018-01-01

β-glucan, the most abundant fungal cell wall polysaccharide, has gained much attention from the scientific community in the last few decades for its fascinating but not yet fully understood immunobiology. Study of this molecule has been motivated by its importance as a pathogen-associated molecular pattern upon fungal infection as well as by its promising clinical utility as biological response modifier for the treatment of cancer and infectious diseases. Its immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils, and natural killer cells. The characteristics of the immune responses generated depend on the cell types and receptors involved. Size and biochemical composition of β-glucans isolated from different sources affect their immunomodulatory properties. The variety of studies using crude extracts of fungal cell wall rather than purified β-glucans renders data difficult to interpret. A better understanding of the mechanisms of purified fungal β-glucan recognition, downstream signaling pathways, and subsequent immune regulation activated, is, therefore, essential not only to develop new antifungal therapy but also to evaluate β-glucan as a putative anti-infective and antitumor mediator. Here, we briefly review the complexity of interactions between fungal β-glucans and mononuclear phagocytes during fungal infections. Furthermore, we discuss and present available studies suggesting how different fungal β-glucans exhibit antitumor and antimicrobial activities by modulating the biologic responses of mononuclear phagocytes, which make them potential candidates as therapeutic agents. PMID:29755450

The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System.

PubMed

Camilli, Giorgio; Tabouret, Guillaume; Quintin, Jessica

2018-01-01

β-glucan, the most abundant fungal cell wall polysaccharide, has gained much attention from the scientific community in the last few decades for its fascinating but not yet fully understood immunobiology. Study of this molecule has been motivated by its importance as a pathogen-associated molecular pattern upon fungal infection as well as by its promising clinical utility as biological response modifier for the treatment of cancer and infectious diseases. Its immune effect is attributed to the ability to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes, macrophages, neutrophils, and natural killer cells. The characteristics of the immune responses generated depend on the cell types and receptors involved. Size and biochemical composition of β-glucans isolated from different sources affect their immunomodulatory properties. The variety of studies using crude extracts of fungal cell wall rather than purified β-glucans renders data difficult to interpret. A better understanding of the mechanisms of purified fungal β-glucan recognition, downstream signaling pathways, and subsequent immune regulation activated, is, therefore, essential not only to develop new antifungal therapy but also to evaluate β-glucan as a putative anti-infective and antitumor mediator. Here, we briefly review the complexity of interactions between fungal β-glucans and mononuclear phagocytes during fungal infections. Furthermore, we discuss and present available studies suggesting how different fungal β-glucans exhibit antitumor and antimicrobial activities by modulating the biologic responses of mononuclear phagocytes, which make them potential candidates as therapeutic agents.

Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy.

PubMed

Daróczy, Judit

2006-01-01

The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema. To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers. 63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection. Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%). Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas).

Banana infecting fungus, Fusarium musae, is also an opportunistic human pathogen: are bananas potential carriers and source of fusariosis?

PubMed

Triest, David; Stubbe, Dirk; De Cremer, Koen; Piérard, Denis; Detandt, Monique; Hendrickx, Marijke

2015-01-01

During re-identification of Fusarium strains in the BCCM™/IHEM fungal collection by multilocus sequence-analysis we observed that five strains, previously identified as Fusarium verticillioides, were Fusarium musae, a species described in 2011 from banana fruits. Four strains were isolated from blood samples or biopsies of immune-suppressed patients and one was isolated from the clinical environment, all originating from different hospitals in Belgium or France, 2001-2008. The F. musae identity of our isolates was confirmed by phylogenetic analysis using reference sequences of type material. Absence of the gene cluster necessary for fumonisin biosynthesis, characteristic to F. musae, was also the case for our isolates. In vitro antifungal susceptibility testing revealed no important differences in their susceptibility compared to clinical F. verticillioides strains and terbinafine was the most effective drug. Additional clinical F. musae strains were searched by performing BLAST queries in GenBank. Eight strains were found, of which six were keratitis cases from the U.S. multistate contact lens-associated outbreak in 2005 and 2006. The two other strains were also from the U.S., causing either a skin infection or sinusitis. This report is the first to describe F. musae as causative agent of superficial and opportunistic, disseminated infections in humans. Imported bananas might act as carriers of F. musae spores and be a potential source of infection with F. musae in humans. An alternative hypothesis is that the natural distribution of F. musae is geographically a lot broader than originally suspected and F. musae is present on different plant hosts. © 2015 by The Mycological Society of America.

Microbial Analysis of Donor Corneoscleral Rims and Storage Media.

PubMed

Tsui, Edmund; Luong, Preston M; Fogel, Jessa; Fogel, Erin S; Zegans, Michael E

2018-05-03

We aim to investigate bacterial and fungal cultures of hypothermic donor corneal storage media (Optisol-GS) and donor rims. All corneal transplants performed from January 1, 2015 to June 30, 2016 by a single surgeon at a single facility were retrospectively reviewed. Aerobic, anaerobic, and fungal cultures were routinely obtained from all donor rims and cornea storage media. Culture results and clinical courses were recorded. Eighty-four corneal transplants were performed. Five of 84 grafts (5.95%) had positive bacteria donor rim cultures. Fungal donor rim cultures were positive in 5/84 grafts (5.95%) of which two grew Candida spp. Storage media bacterial cultures were positive in 2/84 (2.4%) cultures. Storage media fungal cultures were positive in 1/84 (1.2%) cultures. No patients developed any evidence of clinical infection. Given the increasing rates of postkeratoplasty fungal infections, the identification of positive fungal cultures from donor rims and storage media warrants further evaluation of adding antifungals to storage media.

Fungal Mimicry of a Mammalian Aminopeptidase Disables Innate Immunity and Promotes Pathogenicity.

PubMed

Sterkel, Alana K; Lorenzini, Jenna L; Fites, J Scott; Subramanian Vignesh, Kavitha; Sullivan, Thomas D; Wuthrich, Marcel; Brandhorst, Tristan; Hernandez-Santos, Nydiaris; Deepe, George S; Klein, Bruce S

2016-03-09

Systemic fungal infections trigger marked immune-regulatory disturbances, but the mechanisms are poorly understood. We report that the pathogenic yeast of Blastomyces dermatitidis elaborates dipeptidyl-peptidase IVA (DppIVA), a close mimic of the mammalian ectopeptidase CD26, which modulates critical aspects of hematopoiesis. We show that, like the mammalian enzyme, fungal DppIVA cleaved C-C chemokines and GM-CSF. Yeast producing DppIVA crippled the recruitment and differentiation of monocytes and prevented phagocyte activation and ROS production. Silencing fungal DppIVA gene expression curtailed virulence and restored recruitment of CCR2(+) monocytes, generation of TipDC, and phagocyte killing of yeast. Pharmacological blockade of DppIVA restored leukocyte effector functions and stemmed infection, while addition of recombinant DppIVA to gene-silenced yeast enabled them to evade leukocyte defense. Thus, fungal DppIVA mediates immune-regulatory disturbances that underlie invasive fungal disease. These findings reveal a form of molecular piracy by a broadly conserved aminopeptidase during disease pathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Superficial Punctate Keratitis

MedlinePlus

... A viral infection A bacterial infection (including trachoma ) Dry eyes Strong chemicals splashed in the eye Exposure to ... lenses is temporarily discontinued. When the cause is dry eyes, ointments and artificial tears are effective. Artificial tears ...

Disseminated Nosocomial Fungal Infection by Aureobasidium pullulans var. melanigenum: a Case Report

PubMed Central

Bolignano, Giuseppe; Criseo, Giuseppe

2003-01-01

We report on a rare case of disseminated nosocomial fungal infection due to Aureobasidium pullulans var. melanigenum in a severely traumatized patient. Repeated blood and urine cultures yielded multicellular filamentous hyphal structures of varying size accompanied by budding yeast-like-cells of ellipsoidal morphology. The patient became asymptomatic after fluconazole therapy. PMID:12958301

Serious fungal infections in Egypt.

PubMed

Zaki, S M; Denning, D W

2017-06-01

We aimed to estimate the burden of serious fungal infections in Egypt, currently unknown, based on the size of the populations at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports with clearcut denominators. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. The population of Egypt in 2011 was ∼82,500,000; 31% children, and 8% women >60 years of age. Amongst about 21.8 million women aged 15-50 years, recurrent vulvovaginal candidiasis (≥4 episodes/year) is estimated to occur in 1.3 million (3,169/100,000 females). Using a low international average rate of 5/100,000, we estimate 4,127 cases of candidaemia, and 619 patients with intra-abdominal candidiasis. Amongst the survivors of pulmonary tuberculosis (TB) in Egypt in 2012, 319 new cases of chronic pulmonary aspergillosis (CPA) are likely, a prevalence of 1,005 post-TB and a total prevalence estimate of 3,015 CPA patients in all. Asthma is common in Egypt, affecting 9.4% of adults, 5.35 million, and so ABPA and SAFS were estimated in around 162/100,000 and 214/100,000 respectively. Invasive aspergillosis is estimated to affect 495 patients following leukaemia therapy, there are an estimated 37 cases in renal and liver transplant recipients, and an estimated 132 patients develop IA in the context of lung cancer. Amongst 641,000 COPD admissions to hospital each year, 8,337 patients develop IA. The total HIV-infected population is small, with an estimated 6,500 patients, 2,500 not on antiretroviral therapy. Amongst HIV-infected patients, 38 (0.6%) cases of cryptococcal meningitis and 125 (1.9%) cases of Pneumocystis pneumonia are estimated each year. Fungal keratitis is common, with 28-55% (mean 40%) of corneal infections being fungal, an estimated total of 11,550 cases. The present study indicates that 2% of the Egyptian population is affected by fungal infections. The estimates are certainly incomplete, and need further epidemiological and diagnostic studies.

Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature.

PubMed

Benedict, Kaitlin; Chiller, Tom M; Mody, Rajal K

2016-07-01

Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration.

21 CFR 524.1600a - Nystatin, neomycin, thiostrepton, and triamcinolone ointment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... superficial bacterial infections, and for dermatologic disorders characterized by inflammation and dry or... of acute and chronic otitis and interdigital cysts, and in dogs for anal gland infections. (3...

Ecophysiological responses of tall fescue genotypes to fungal endophyte infection and elevated temperature and precipitation

USDA-ARS?s Scientific Manuscript database

Tall fescue (Schedonorus arundinaceus) can form a symbiosis with the fungal endophyte, Epichloë coenophiala, whose presence can benefit the plant, depending on plant and fungal genetics and prevailing environmental conditions. Despite this symbiosis having agricultural, economic and ecological impor...

Biotechnological production of inducible defense-related proteins in edible radish (raphanus sativus) found in Nepal.

PubMed

Khanal, Praval; Karmacharya, Anil; Sharma, Shishir; Nepal, Ashwini K; Shrestha, Kanti

2014-01-01

Fungal infection in plant leads to use of many hazardous antifungal chemicals. Alternative to these chemicals, defense related antifungal proteins can be used in case of fungal diseases. An experiment was done in two varieties of edible radish (Raphanus sativus var. Pyuthane Raato and Raphanus sativus var. all season) with aims to produce defense protein within the plant, to identify and perform molecular characterization of those antifungal proteins. The next aim was to compare the antifungal property of those proteins with commercially available synthetic pesticides. Both varieties of radish were infected with fungi (Alternaria alternata and Fusarium oxysporum). Protein samples were isolated from leaves following the standard protocol as described for β-glucuronidase (GUS) assay and were run along with the standard protein marker of 10-250kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to identify and molecularly characterize them. An additional band in the range of 37-50kDa was observed in the fungal infected samples, which was not seen on uninfected samples. The antifungal assay was carried out for every sample in 96 wells microtitre plate. The extracted protein samples from fungal inoculated plants showed the significant inhibition of fungal growth compared to other samples. On the basis of molecular weight and their antifungal properties, the protein samples from the fungal infected plant were found to be PR2 (Glucanase) and PR3 (Chitinase). Defense related proteins were successfully produced in two varieties of radish found in Nepal. The use of such biologically produced proteins may reduce the use of biologically harmful synthetic pesticides.

Serious fungal infections in the Philippines.

PubMed

Batac, M C R; Denning, D

2017-06-01

The Philippines is a low middle-income, tropical country in Southeast Asia. Infectious diseases remain the main causes of morbidity, including tuberculosis. AIDS/HIV prevalence is still low at <1%, but is rapidly increasing. Fungal disease surveillance has not been done, and its burden has never been estimated. This becomes more important as the population of immunocompromised patients increases, drawn from patients with AIDS, TB, malignancies, and autoimmune diseases requiring chronic steroid use. Using the methodology of the LIFE program ( www.LIFE-worldwide.org ), estimates were derived from data gathered from WHO, UNAIDS, Philippine Health Statistics 2011, Philippine Dermatological Society Health Information System database, HIV/AIDS and ART registry of the Philippines, epidemiological studies such as The TREAT Asia HIV Observational Database 2005, and personal communication. Aspergillosis and candidiasis were the top causes of fungal infections in the Philippines. Chronic pulmonary aspergillosis (CPA), drawn from the number of tuberculosis patients, affects 77,172 people. Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) frequencies, which were derived from the number of asthmatic patients, affect 121,113 and 159,869 respectively. Recurrent vulvovaginal candidiasis (RVVC) affects 1,481,899 women. Other estimates were cryptococcal meningitis 84, Pneumocystis pneumonia 391, oral candidiasis 3,467, esophageal candidiasis 1,522 (all in HIV-infected people), invasive aspergillosis (IA) 3,085, candidemia 1,968, candida peritonitis 246, mucormycosis 20, fungal keratitis 358, tinea capitis 846 and mycetoma 97 annually. A total of 1,852,137 (1.9% of population) are afflicted with a serious fungal infection. Epidemiological studies are needed to validate these estimates, facilitating appropriate medical care of patients and proper prioritization of limited resources.

Escherichia coli pneumonia in combination with fungal sinusitis and meningitis in a tsunami survivor after the Great East Japan Earthquake.

PubMed

Igusa, Ryotaro; Narumi, Sodai; Murakami, Koji; Kitawaki, Yuko; Tamii, Toru; Kato, Masahiro; Sato, Mineshige; Tsuboi, Masahiro; Ota, Kozo

2012-07-01

Individuals who survive near drowning often suffer from complicated infections, including multi-organ and polymicrobial events. This pattern may be especially pronounced among patients exposed to infectious agents during catastrophic events like that of the Great East Japan Earthquake and the associated tsunami disaster. We report here on a patient who presented with Escherichia coli (E. coli) pneumonia in combination with fungal sinusitis and meningitis. A 73-year-old woman survived the tsunami that engulfed the Sanriku coast. By the time of hospital admission, the patient exhibited high fever, severe cough, and sputum production. Chest X-ray and CT scan showed consolidation in the left upper lobe. Administration of an antibacterial agent improved this pneumonia. However, the patient's consciousness was increasingly impaired. Brain CT showed the low-density lesions and partial high-density spot in the sinus, which suggests the fungal infection. MRI showed the inflammation in the sinus spread into the central nerve system. The examination of the cerebrospinal fluid showed the low glucose level, high mononuclear cell count, and highβ-D glucan level, the findings of which supported the diagnosis of fungal meningitis. Although the patient improved temporarily in response to combination treatment with anti-fungal agents, no further improvement was seen. In conclusion, this patient, who suffered from infections of pneumonia, sinusitis, and meningitis, presented a quite rare clinical progress. We propose that fungal infection should be taken into consideration in individuals who suffered near drowning, a profile expected to be frequent among tsunami survivors.

Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae from Arabidopsis leaves for stage-specific transcriptome analysis.

PubMed

Takahara, Hiroyuki; Dolf, Andreas; Endl, Elmar; O'Connell, Richard

2009-08-01

Generation of stage-specific cDNA libraries is a powerful approach to identify pathogen genes that are differentially expressed during plant infection. Biotrophic pathogens develop specialized infection structures inside living plant cells, but sampling the transcriptome of these structures is problematic due to the low ratio of fungal to plant RNA, and the lack of efficient methods to isolate them from infected plants. Here we established a method, based on fluorescence-activated cell sorting (FACS), to purify the intracellular biotrophic hyphae of Colletotrichum higginsianum from homogenates of infected Arabidopsis leaves. Specific selection of viable hyphae using a fluorescent vital marker provided intact RNA for cDNA library construction. Pilot-scale sequencing showed that the library was enriched with plant-induced and pathogenicity-related fungal genes, including some encoding small, soluble secreted proteins that represent candidate fungal effectors. The high purity of the hyphae (94%) prevented contamination of the library by sequences derived from host cells or other fungal cell types. RT-PCR confirmed that genes identified in the FACS-purified hyphae were also expressed in planta. The method has wide applicability for isolating the infection structures of other plant pathogens, and will facilitate cell-specific transcriptome analysis via deep sequencing and microarray hybridization, as well as proteomic analyses.

Evaluation of fluorescence in situ hybridisation (FISH) for the detection of fungi directly from blood cultures and cerebrospinal fluid from patients with suspected invasive mycoses.

PubMed

Da Silva, Roberto Moreira; Da Silva Neto, João Ricardo; Santos, Carla Silvana; Frickmann, Hagen; Poppert, Sven; Cruz, Kátia Santana; Koshikene, Daniela; De Souza, João Vicente Braga

2015-01-31

The aim of this study was to evaluate the diagnostic performance of in-house FISH (fluorescence in situ hybridisation) procedures for the direct identification of invasive fungal infections in blood cultures and cerebrospinal fluid (CSF) samples and to compare these FISH results with those obtained using traditional microbiological techniques and PCR targeting of the ITS1 region of the rRNA gene. In total, 112 CSF samples and 30 positive blood cultures were investigated by microscopic examination, culture, PCR-RFLP and FISH. The sensitivity of FISH for fungal infections in CSF proved to be slightly better than that of conventional microscopy (India ink) under the experimental conditions, detecting 48 (instead of 46) infections in 112 samples. The discriminatory powers of traditional microbiology, PCR-RFLP and FISH for fungal bloodstream infections were equivalent, with the detection of 14 fungal infections in 30 samples. However, the mean times to diagnosis after the detection of microbial growth by automated blood culture systems were 5 hours, 20 hours and 6 days for FISH, PCR-RFLP and traditional microbiology, respectively. The results demonstrate that FISH is a valuable tool for the identification of invasive mycoses that can be implemented in the diagnostic routine of hospital laboratories.

Neutrophil extracellular traps in fungal infection.

PubMed

Urban, Constantin F; Nett, Jeniel E

2018-04-03

Fungal infections are a continuously increasing problem in modern health care. Understanding the complex biology of the emerging pathogens and unraveling the mechanisms of host defense may form the basis for the development of more efficient diagnostic and therapeutic tools. Neutrophils play a pivotal role in the defense against fungal pathogens. These phagocytic hunters migrate towards invading fungal microorganisms and eradicate them by phagocytosis, oxidative burst and release of neutrophil extracellular traps (NETs). In the last decade, the process of NET formation has received unparalleled attention, with numerous studies revealing the relevance of this neutrophil function for control of various mycoses. Here, we describe NET formation and summarize its role as part of the innate immune defense against fungal pathogens. We highlight factors influencing the formation of these structures and molecular mechanisms employed by fungi to impair the formation of NETs or subvert their antifungal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

More than a colour change: insect melanism, disease resistance and fecundity.

PubMed

Dubovskiy, I M; Whitten, M M A; Kryukov, V Y; Yaroslavtseva, O N; Grizanova, E V; Greig, C; Mukherjee, K; Vilcinskas, A; Mitkovets, P V; Glupov, V V; Butt, T M

2013-07-22

A 'dark morph' melanic strain of the greater wax moth, Galleria mellonella, was studied for its atypical, heightened resistance to infection with the entomopathogenic fungus, Beauveria bassiana. We show that these insects exhibit multiple intraspecific immunity and physiological traits that distinguish them from a non-melanic, fungus-susceptible morph. The melanic and non-melanic morphs were geographical variants that had evolved different, independent defence strategies. Melanic morphs exhibit a thickened cuticle, higher basal expression of immunity- and stress-management-related genes, higher numbers of circulating haemocytes, upregulated cuticle phenoloxidase (PO) activity concomitant with conidial invasion, and an enhanced capacity to encapsulate fungal particles. These insects prioritize specific augmentations to those frontline defences that are most likely to encounter invading pathogens or to sustain damage. Other immune responses that target late-stage infection, such as haemolymph lysozyme and PO activities, do not contribute to fungal tolerance. The net effect is increased larval survival times, retarded cuticular fungal penetration and a lower propensity to develop haemolymph infections when challenged naturally (topically) and by injection. In the absence of fungal infection, however, the heavy defence investments made by melanic insects result in a lower biomass, decreased longevity and lower fecundity in comparison with their non-melanic counterparts. Although melanism is clearly correlated with increased fungal resistance, the costly mechanisms enabling this protective trait constitute more than just a colour change.

Successful Antibiotic Treatment of Severe Staphylococcal Infection of a Long Stent Graft in the Superficial Femoral Artery with Graft Preservation in the Long Term

DOE Office of Scientific and Technical Information (OSTI.GOV)

Treitl, Marcus, E-mail: Marcus.Treitl@med.uni-muenchen.de; Rademacher, Antje; Becker-Lienau, Johanna

2011-06-15

Introduction: Bacterial infection of endovascular stent grafts is a serious condition, regularly leading to graft replacement by open bypass surgery.Case ReportWe describe the case of a staphylococcal infection of a 150-mm covered stent graft (Gore Viabahn), placed in the superficial femoral artery. Stent graft infection was successfully treated by oral administration of penicillinase-resistant flucloxacillin and the lipopeptide daptomycin with complete graft preservation, not requiring surgical treatment. During 1-year follow-up, the graft infection did not reappear. However, the patient developed restenosis at the proximal margin of the stent with recurrence of mild claudication, so far treated conservatively. Conclusion: With the increasedmore » use of covered stent grafts in the peripheral vasculature, the frequency of graft infection will increase. We demonstrate that with newly developed antibiotics, it is possible to treat this severe complication conservatively, with complete graft preservation and without the need for bypass surgery in selected cases.« less

[Antifungal therapy for infants, children and adolescents with suspected or documented invasive fungal infection].

PubMed

Odio, C M

2010-04-01

Fungal nosocomial infections have gradually and consistently increased since the 90s.This increasing threat is closely related with the growing number of people with immune system disorders and their survival. It is also related with the destruction of their physical barriers against infection due to the use of cytotoxic drugs or invasive procedures, such is the case of cancer patients and bone marrow and solid organ transplant patients. Increased survival of patients with congenital or acquired immunodeficiency, premature babies and patients with complex congenital malformations, especially in the gastrointestinal tract, also add up to this scenario. The occurrence of yeast and filamentous fungi infections, especially of the Candida species, has been on the rise. Azole agents overuse, especially fluconazole, for the treatment and prophylaxis of fungal infections has put selective pressure on Candida spp. which resulted in an increase of non-albican species such as C. krusei, C. glabrata and C. famata, among others, as well as their growing resistance to these antifungal agents.

Mucormycosis: a rare fungal infection in tornado victims.

PubMed

Austin, Cindy L; Finley, Phillip J; Mikkelson, Debbie R; Tibbs, Brian

2014-01-01

This article reviews four immunocompetent patients who developed a rare fungal infection, mucormycosis, secondary to multiple traumatic injuries sustained during an EF-5 tornado in Joplin, MO. Commonly found in soil and decaying organic matter, mucorales are fungi associated with soft tissue and cutaneous infections. Onset of this fungal infection can occur without clinical signs, presenting several days to several weeks after injury, delaying diagnosis. A multidisciplinary treatment approach including aggressive antifungal therapy and aggressive surgical debridement is critical. This diagnosis should be considered in all patients presenting with injuries sustained from high-velocity embedment of debris such as natural disasters or explosions. We present four cases of mucormycosis, species Apophysomyces trapeziformis. Data reported includes predisposing factors, number of days between injury and diagnosis of mucormycosis, surgical treatment, antifungal therapy, outcomes, and potential risk factors that may have contributed to the development of mucormycosis.

[Invasive fungal disease due to Scedosporium, Fusarium and mucorales].

PubMed

Pemán, Javier; Salavert, Miguel

2014-01-01

The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. Copyright © 2014. Published by Elsevier Espana.

CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System

PubMed Central

Swamydas, Muthulekha; Rodriguez, Carlos A.; Lim, Jean K.; Mendez, Laura M.; Fink, Danielle L.; Hsu, Amy P.; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M.; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K.; Belhorn, Thomas H.; Weimer, Eric T.; Hernandez, Michelle L.; Hohl, Tobias M.; Kuhns, Douglas B.; Lionakis, Michail S.

2015-01-01

Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9 -/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9 -/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

Repurposing antipsychotic drugs into antifungal agents: Synergistic combinations of azoles and bromperidol derivatives in the treatment of various fungal infections.

PubMed

Holbrook, Selina Y L; Garzan, Atefeh; Dennis, Emily K; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

2017-10-20

As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles. Exploring combination therapy that involves the current azoles and another drug has been shown to be a promising strategy. Haloperidol and its derivative, bromperidol, were originally discovered as antipsychotics. Herein, we synthesize and report a series of bromperidol derivatives and their synergistic antifungal interactions in combination with a variety of current azole antifungals against a wide panel of fungal pathogens. We further select two representative combinations and confirm the antifungal synergy by performing time-kill assays. Furthermore, we evaluate the ability of selected combinations to destroy fungal biofilm. Finally, we perform mammalian cytotoxicity assays with the representative combinations against three mammalian cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Interaction of entomopathogenic fungi with the host immune system.

PubMed

Qu, Shuang; Wang, Sibao

2018-06-01

Entomopathogenic fungi can invade wide range of insect hosts in the natural world and have been used as environmentally friendly alternatives to chemical insecticides for pest control. Studies of host-pathogen interactions provide valuable insights into the coevolutionay arms race between fungal pathogens and their hosts. Entomopathogenic fungi have evolved a series of sophisticated strategies to counter insect immune defenses. In response to fungal infection, insect hosts rely on behavior avoidance, physical barrier and innate immune defenses in the fight against invading pathogens. The insect cuticle acts as the first physical barrier against pathogens. It is an inhospitable physiological environment that contains chemicals (e.g., antimicrobial peptides and reactive oxygen species), which inhibit fungal growth. In addition, innate immune responses, including cellular immunity and humoral immunity, play critical roles in preventing fungal infection. In this review, we outline the current state of our knowledge of insect defenses to fungal infection and discuss the strategies by which entomopathogenic fungi counter the host immune system. Increased knowledge regarding the molecular interactions between entomopathogenic fungi and the insect host could provide new strategies for pest management. Copyright © 2018 Elsevier Ltd. All rights reserved.

Morbidity associated with 30-day surgical site infection following nonshunt pediatric neurosurgery

PubMed Central

Sherrod, Brandon A.; Rocque, Brandon G.

2017-01-01

Objective Morbidity associated with surgical site infection (SSI) following nonshunt pediatric neurosurgical procedures is poorly understood. The purpose of this study was to analyze acute morbidity and mortality associated with SSI after nonshunt pediatric neurosurgery using a nationwide cohort. Methods The authors reviewed data from the American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-P) 2012–2014 database, including all neurosurgical procedures performed on pediatric patients. Procedures were categorized by Current Procedural Terminology (CPT) codes. CSF shunts were excluded. Deep and superficial SSIs occurring within 30 days of an index procedure were identified. Deep SSIs included deep wound infections, intracranial abscesses, meningitis, osteomyelitis, and ventriculitis. The following outcomes occurring within 30 days of an index procedure were analyzed, along with postoperative time to complication development: sepsis, wound disruption, length of postoperative stay, readmission, reoperation, and death. Results A total of 251 procedures associated with a 30-day SSI were identified (2.7% of 9296 procedures). Superficial SSIs were more common than deep SSIs (57.4% versus 42.6%). Deep SSIs occurred more frequently after epilepsy or intracranial tumor procedures. Superficial SSIs occurred more frequently after skin lesion, spine, Chiari decompression, craniofacial, and myelomeningocele closure procedures. The mean (± SD) postoperative length of stay for patients with any SSI was 9.6 ± 14.8 days (median 4 days). Post-SSI outcomes significantly associated with previous SSI included wound disruption (12.4%), sepsis (15.5%), readmission (36.7%), and reoperation (43.4%) (p < 0.001 for each). Post-SSI sepsis rates (6.3% vs 28.0% for superficial versus deep SSI, respectively; p < 0.001), wound disruption rates (4.9% vs 22.4%, p < 0.001), and reoperation rates (23.6% vs 70.1%, p < 0.001) were significantly greater for patients with deep SSIs. Postoperative length of stay in patients discharged before SSI development was not significantly different for deep versus superficial SSI (4.2 ± 2.7 vs 3.6 ± 2.4 days, p = 0.094). No patient with SSI died within the first 30 days after surgery. Conclusions Thirty-day SSI is associated with significant 30-day morbidity in pediatric patients undergoing nonshunt neurosurgery. Rates of SSI-associated complications are significantly lower in patients with superficial infection than in those with deep infection. There were no cases of SSI-related mortality within 30 days of the index procedure. PMID:28186474

Epidemiology of invasive fungal infections in patients with acquired immunodeficiency syndrome at a reference hospital for infectious diseases in Brazil.

PubMed

de Oliveira, Renata Buccheri; Atobe, Jane Harumi; Souza, Simone Aparecida; de Castro Lima Santos, Daniel Wagner

2014-08-01

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20-25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.

Vertebral Osteomyelitis and Acinetobacter Spp. Paravertebral Soft Tissue Infection in a 4-Year-Old Boy With X-Linked Chronic Granulomatous Disease.

PubMed

Vignesh, Pandiarajan; Bhattad, Sagar; Shandilya, Jitendra-Kumar; Vyas, Sameer; Garg, Rashi; Rawat, Amit

2016-09-01

Vertebral osteomyelitis is known to occur in chronic granulomatous disease, a phagocytic disorder and the etiology is usually a fungus. Indolent spread of fungal infection from lungs to adjacent ribs and vertebra often results in persistent pneumonia and vertebral deformities. We report a 4-year-old boy with chronic cough and kyphosis, who had a fungal vertebral osteomyelitis and Acinetobacter spp. paravertebral soft tissue infection related to X-linked chronic granulomatous disease.

Review article: fungal microbiota and digestive diseases.

PubMed

Wang, Z K; Yang, Y S; Stefka, A T; Sun, G; Peng, L H

2014-04-01

The role of the fungal microbiota in digestive diseases is poorly defined, but is becoming better understood due to advances in metagenomics. To review the gastrointestinal fungal microbiota and its relationship with digestive diseases. Search of the literature using PubMed and MEDLINE databases. Subject headings including 'fungal-bacterial interactions', 'mycotoxins', 'immunity to fungi', 'fungal infection', 'fungal microbiota', 'mycobiome' and 'digestive diseases' were used. The fungal microbiota is an integral part of the gastrointestinal microecosystem with up to 10(6) microorganisms per gram of faeces. Next-generation sequencing of the fungal 18S rRNA gene has allowed better characterisation of the gastrointestinal mycobiome. Numerous interactions between fungi and bacteria and the complex immune response to gastrointestinal commensal or pathogenic fungi all impact on the pathophysiology of inflammatory bowel disease and other gastrointestinal inflammatory entities such as peptic ulcers. Mycotoxins generated as fungal metabolites contribute to disturbances of gastrointestinal barrier and immune functions and are associated with chronic intestinal inflammatory conditions as well as hepatocellular and oesophagogastric cancer. Systemic and gastrointestinal disease can also lead to secondary fungal infections. Fungal genomic databases and methodologies need to be further developed and will allow a much better understanding of the diversity and function of the mycobiome in gastrointestinal inflammation, tumourigenesis, liver cirrhosis and transplantation, and its alteration as a consequence of antibiotic therapy and chemotherapy. The fungal microbiota and its metabolites impact gastrointestinal function and contribute to the pathogenesis of digestive diseases. Further metagenomic analyses of the gastrointestinal mycobiome in health and disease is needed. © 2014 John Wiley & Sons Ltd.

Histopathologic Diagnosis of Fungal Infections in the 21st Century

PubMed Central

Guarner, Jeannette; Brandt, Mary E.

2011-01-01

Summary: Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs. PMID:21482725

IMAGING MASS SPECTROMETRY OF A CORAL MICROBE INTERACTION WITH FUNGI

PubMed Central

ZHAO, XILING; LIU, WEI-TING; APARICIO, MARYSTELLA; ATENCIO, LIBRADA; BALLESTEROS, JAVIER; SÁNCHEZ, JOEL; GAVILÁN, RONNIE G.; GUTIÉRREZ, MARCELINO; DORRESTEIN, PIETER C.

2013-01-01

Fungal infections are increasing worldwide, including in the aquatic environment. Microbiota that coexist with marine life can provide protection against fungal infections by secretion of metabolites with antifungal properties. Our laboratory has developed mass spectrometric methodologies with the goal of improving our functional understanding of microbial metabolites and guiding the discovery process of anti-infective agents from natural sources. GA40, a Bacillus amyloliquefaciens strain isolated from an octocoral in Panama, displayed antifungal activity against various terrestrial and marine fungal strains. Using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), the molecular species produced by this microbe were visualized in a side-by-side interaction with two representative fungal strains, Aspergillus fumigatus and Aspergillus niger. The visualization was performed directly on the agar without the need for extraction. By comparison of spatial distributions, relative intensities and m/z values of GA40 secreted metabolites in the fungal interactions versus singly grown control colonies, we obtained insight into the antifungal activity of secreted metabolites. Annotation of GA40 metabolites observed in MALDI-IMS was facilitated by MS/MS networking analysis, a mass spectrometric technique that clusters metabolites with similar MS/MS fragmentation patterns. This analysis established that the predominant GA40 metabolites belong to the iturin family. In a fungal inhibition assay of A. fumigatus, the GA40 iturin metabolites were found to be responsible for the antifungal properties of this Bacillus strain. PMID:23881443

Infection with a Shoot-Specific Fungal Endophyte (Epichloë) Alters Tall Fescue Soil Microbial Communities.

PubMed

Rojas, Xavier; Guo, Jingqi; Leff, Jonathan W; McNear, David H; Fierer, Noah; McCulley, Rebecca L

2016-07-01

Tall fescue (Schedonorus arundinaceus) is a widespread grass that can form a symbiotic relationship with a shoot-specific fungal endophyte (Epichloë coenophiala). While the effects of fungal endophyte infection on fescue physiology and ecology have been relatively well studied, less attention has been given to how this relationship may impact the soil microbial community. We used high-throughput DNA sequencing and phospholipid fatty acid analysis to determine the structure and biomass of microbial communities in both bulk and rhizosphere soils from tall fescue stands that were either uninfected with E. coenophiala or were infected with the common toxic strain or one of several novel strains of the endophyte. We found that rhizosphere and bulk soils harbored distinct microbial communities. Endophyte presence, regardless of strain, significantly influenced soil fungal communities, but endophyte effects were less pronounced in prokaryotic communities. E. coenophiala presence did not change total fungal biomass but caused a shift in soil and rhizosphere fungal community composition, increasing the relative abundance of taxa within the Glomeromycota phylum and decreasing the relative abundance of genera in the Ascomycota phylum, including Lecanicillium, Volutella, Lipomyces, Pochonia, and Rhizoctonia. Our data suggests that tripartite interactions exist between the shoot endophyte E. coenophiala, tall fescue, and soil fungi that may have important implications for the functioning of soils, such as carbon storage, in fescue-dominated grasslands.

Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids.

PubMed

Mor, Visesato; Rella, Antonella; Farnoud, Amir M; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B; Wiederhold, Nathan P; Fothergill, Annette W; Kirkpatrick, William R; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L; Luberto, Chiara; Nimrichter, Leonardo; Del Poeta, Maurizio

2015-06-23

Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N'-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N'-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals. Copyright © 2015 Mor et al.

Pneumodissection for skin protection in image-guided cryoablation of superficial musculoskeletal tumours.

PubMed

Maybody, Majid; Tang, Peter Q; Moskowitz, Chaya S; Hsu, Meier; Yarmohammadi, Hooman; Boas, F Edward

2017-03-01

Pneumodissection is described as a simple method for preventing skin injury during cryoablation of superficial musculoskeletal tumours. Superficial tumour cryoablations performed from 2009 to 2015 were retrospectively reviewed. Pneumodissection was performed in 13 patients when the shortest tumour-skin distance was less than 25 mm. Indications were pain palliation (n = 9) and local tumour control (n = 4). Patients, target tumours, technical characteristics and complications up to 60 days post ablation were reviewed. The ice ball-skin distances with and without pneumodissection were compared by a paired t-test and further assessed for association with covariates using ANCOVA. Technical success for ablation was 12 of 13. The mean shortest tumour-skin distance was 15.0 mm (3.2-24.5 mm). The mean thickness of pneumodissection was 9.6 mm (5.2-16.6 mm) resulting in mean elevation of skin of 3.4 mm (1.2-5.3 mm). Mean shortest ice ball-skin distance after pneumodissection was 10.5 mm (4.2-19.7 mm). No infection or systemic air embolism was noted. No intraprocedural frostbite was observed. Pneumodissection is feasible, effective and safe in protecting the skin during image-guided cryoablation of superficial tumours. • Frostbite during image-guided cryoablation of superficial tumours is commonly under-reported. • Frostbites are painful and may introduce infection into the superficial ablation zone. • Warm compress, saline and CO 2 have shortcomings in protecting the skin. • Pneumodissection is free, readily available, easy to use and safe and effective.

Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

PubMed

Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

2016-02-01

Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

Fungal and Parasitic Infections of the Eye

PubMed Central

Klotz, Stephen A.; Penn, Christopher C.; Negvesky, Gerald J.; Butrus, Salim I.

2000-01-01

The unique structure of the human eye as well as exposure of the eye directly to the environment renders it vulnerable to a number of uncommon infectious diseases caused by fungi and parasites. Host defenses directed against these microorganisms, once anatomical barriers are breached, are often insufficient to prevent loss of vision. Therefore, the timely identification and treatment of the involved microorganisms are paramount. The anatomy of the eye and its surrounding structures is presented with an emphasis upon the association of the anatomy with specific infection of fungi and parasites. For example, filamentous fungal infections of the eye are usually due to penetrating trauma by objects contaminated by vegetable matter of the cornea or globe or, by extension, of infection from adjacent paranasal sinuses. Fungal endophthalmitis and chorioretinitis, on the other hand, are usually the result of antecedent fungemia seeding the ocular tissue. Candida spp. are the most common cause of endogenous endophthalmitis, although initial infection with the dimorphic fungi may lead to infection and scarring of the chorioretina. Contact lens wear is associated with keratitis caused by yeasts, filamentous fungi, and Acanthamoebae spp. Most parasitic infections of the eye, however, arise following bloodborne carriage of the microorganism to the eye or adjacent structures. PMID:11023963

Brief review on the effect of low-power laser irradiation on neutrophils with emphasis on emerging fungal infections

NASA Astrophysics Data System (ADS)

Sperandio, F. F.; Bani, G. M. A. C.; Mendes, A. C. S. C.; Brigagão, M. R. P. L.; Santos, G. B.; Malaquias, L. C. C.; Chavasco, J. K.; Verinaud, L. M.; Burger, E.

2015-03-01

Polymorphonuclear neutrophils (PMN) participate in an active way in the innate immunity developed after the fungal infection paracoccidioidomycosis (PCM). Nevertheless, the sole participation of neutrophils is not sufficient to eradicate PCM`s pathogenic fungus: Paracoccidioides brasiliensis (Pb). In that way, we aimed to develop a treatment capable of stimulating PMN to the site of injury through low-level laser therapy (LLLT). (LLLT) is safe to use and has not been linked to microorganism resistance so far; in addition, based on previous studies we understand that LLLT may be useful to treat several medical conditions through the stimulation and activation of certain types of cells. This brief review is based on the novel attempt of activating PMN against a fungal infection.

An age-structured model to evaluate the potential of novel malaria-control interventions: a case study of fungal biopesticide sprays

PubMed Central

Hancock, P.A; Thomas, M.B; Godfray, H.C.J

2008-01-01

It has recently been proposed that mosquito vectors of human diseases, particularly malaria, may be controlled by spraying with fungal biopesticides that increase the rate of adult mortality. Though fungal pathogens do not cause instantaneous mortality, they can kill mosquitoes before they are old enough to transmit disease. A model is developed (i) to explore the potential for fungal entomopathogens to reduce significantly infectious mosquito populations, (ii) to assess the relative value of the many different fungal strains that might be used, and (iii) to help guide the tactical design of vector-control programmes. The model follows the dynamics of different classes of adult mosquitoes with the risk of mortality due to the fungus being assumed to be a function of time since infection (modelled using the Weibull distribution). It is shown that substantial reductions in mosquito numbers are feasible for realistic assumptions about mosquito, fungus and malaria biology and moderate to low daily fungal infection probability. The choice of optimal fungal strain and spraying regime is shown to depend on local mosquito and malaria biology. Fungal pathogens may also influence the ability of mosquitoes to transmit malaria and such effects are shown to further reduce vectorial capacity. PMID:18765347

Systems Biology Approaches for Host–Fungal Interactions: An Expanding Multi-Omics Frontier

PubMed Central

Culibrk, Luka; Croft, Carys A.

2016-01-01

Abstract Opportunistic fungal infections are an increasing threat for global health, and for immunocompromised patients in particular. These infections are characterized by interaction between fungal pathogen and host cells. The exact mechanisms and the attendant variability in host and fungal pathogen interaction remain to be fully elucidated. The field of systems biology aims to characterize a biological system, and utilize this knowledge to predict the system's response to stimuli such as fungal exposures. A multi-omics approach, for example, combining data from genomics, proteomics, metabolomics, would allow a more comprehensive and pan-optic “two systems” biology of both the host and the fungal pathogen. In this review and literature analysis, we present highly specialized and nascent methods for analysis of multiple -omes of biological systems, in addition to emerging single-molecule visualization techniques that may assist in determining biological relevance of multi-omics data. We provide an overview of computational methods for modeling of gene regulatory networks, including some that have been applied towards the study of an interacting host and pathogen. In sum, comprehensive characterizations of host–fungal pathogen systems are now possible, and utilization of these cutting-edge multi-omics strategies may yield advances in better understanding of both host biology and fungal pathogens at a systems scale. PMID:26885725

Fungal endophytes which invade insect galls: insect pathogens, benign saprophytes, or fungal inquilines?

PubMed

Wilson, Dennis

1995-08-01

Fungi are frequently found within insect galls. However, the origin of these fungi, whether they are acting as pathogens, saprophytes invading already dead galls, or fungal inquilines which invade the gall but kill the gall maker by indirect means, is rarely investigated. A pathogenic role for these fungi is usually inferred but never tested. I chose the following leaf-galling-insect/host-plant pairs (1) a cynipid which forms two-chambered galls on the veins of Oregon white oak, (2) a cynipid which forms single-chambered galls on California coast live oak, and (3) an aphid which forms galls on narrowleaf cottonwood leaves. All pairs were reported to have fungi associated with dead insects inside the gall. These fungi were cultured and identified. For the two cynipids, all fungi found inside the galls were also present in the leaves as fungal endophytes. The cottonwood leaves examined did not harbor fungal endophytes. For the cynipid on Oregon white oak, the fungal endophyte grows from the leaf into the gall and infects all gall tissue but does not directly kill the gall maker. The insect dies as a result of the gall tissue dying from fungal infection. Therefore, the fungus acts as an inquiline. Approximately 12.5% of these galls die as a result of invasion by the fungal endophyte.

Host Control of Fungal Infections: Lessons from Basic Studies and Human Cohorts.

PubMed

Lionakis, Michail S; Levitz, Stuart M

2018-04-26

In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients.

Yeast Infection (Vaginal)

MedlinePlus

Yeast infection (vaginal) Overview A vaginal yeast infection is a fungal infection that causes irritation, discharge and intense itchiness ... symptoms Causes The fungus candida causes a vaginal yeast infection. Your vagina naturally contains a balanced mix of yeast, including ...

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

PubMed Central

Hein, Kyaw Zaw; Takahashi, Hitoshi; Tsumori, Toshiko; Yasui, Yukihiko; Nanjoh, Yasuko; Toga, Tetsuo; Wu, Zhihong; Grötzinger, Joachim; Jung, Sascha; Wehkamp, Jan; Schroeder, Bjoern O.; Schroeder, Jens M.; Morita, Eishin

2015-01-01

The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn2+, suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn2+-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn2+-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn2+-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi. PMID:26438863

Renal fungal bezoar owing to Geotrichum candidum

PubMed Central

Yegneswaran Prakash, Peralam; Seetaramaiah, Venkatesh K; Thomas, Joseph; Khanna, Vinay; Rao, Sugandhi P

2012-01-01

Geotrichum candidum is yeast like fungi that cause infections in immunocompromised patients. We report a case of renal fungal ball with Geotrichum candidum in a 27 yr. old women post-partum. This case to our knowledge is the first case of renal fungal bezoar due to Geotrichum candidum reported in India. PMID:27330935

IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa.

PubMed

Altmeier, Simon; Toska, Albulena; Sparber, Florian; Teijeira, Alvaro; Halin, Cornelia; LeibundGut-Landmann, Salomé

2016-09-01

Mucosal infections with Candida albicans belong to the most frequent forms of fungal diseases. Host protection is conferred by cellular immunity; however, the induction of antifungal immunity is not well understood. Using a mouse model of oropharyngeal candidiasis (OPC) we show that interleukin-1 receptor (IL-1R) signaling is critical for fungal control at the onset of infection through its impact on neutrophils at two levels. We demonstrate that both the recruitment of circulating neutrophils to the site of infection and the mobilization of newly generated neutrophils from the bone marrow depended on IL-1R. Consistently, IL-1R-deficient mice displayed impaired chemokine production at the site of infection and defective secretion of granulocyte colony-stimulating factor (G-CSF) in the circulation in response to C. albicans. Strikingly, endothelial cells were identified as the primary cellular source of G-CSF during OPC, which responded to IL-1α that was released from keratinocytes in the infected tissue. The IL-1-dependent crosstalk between two different cellular subsets of the nonhematopoietic compartment was confirmed in vitro using a novel murine tongue-derived keratinocyte cell line and an established endothelial cell line. These data establish a new link between IL-1 and granulopoiesis in the context of fungal infection. Together, we identified two complementary mechanisms coordinating the neutrophil response in the oral mucosa, which is critical for preventing fungal growth and dissemination, and thus protects the host from disease.

Elucidating the Role of Effectors in Plant-Fungal Interactions: Progress and Challenges

PubMed Central

Selin, Carrie; de Kievit, Teresa R.; Belmonte, Mark F.; Fernando, W. G. Dilantha

2016-01-01

Pathogenic fungi have diverse growth lifestyles that support fungal colonization on plants. Successful colonization and infection for all lifestyles depends upon the ability to modify living host plants to sequester the necessary nutrients required for growth and reproduction. Secretion of virulence determinants referred to as “effectors” is assumed to be the key governing factor that determines host infection and colonization. Effector proteins are capable of suppressing plant defense responses and alter plant physiology to accommodate fungal invaders. This review focuses on effector molecules of biotrophic and hemibiotrophic plant pathogenic fungi, and the mechanism required for the release and uptake of effector molecules by the fungi and plant cells, respectively. We also place emphasis on the discovery of effectors, difficulties associated with predicting the effector repertoire, and fungal genomic features that have helped promote effector diversity leading to fungal evolution. We discuss the role of specific effectors found in biotrophic and hemibiotrophic fungi and examine how CRISPR/Cas9 technology may provide a new avenue for accelerating our ability in the discovery of fungal effector function. PMID:27199930

Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature

PubMed Central

Benedict, Kaitlin; Chiller, Tom M.; Mody, Rajal K.

2017-01-01

Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration. PMID:27074753

The Endosymbiont Arsenophonus Is Widespread in Soybean Aphid, Aphis glycines, but Does Not Provide Protection from Parasitoids or a Fungal Pathogen

PubMed Central

Wulff, Jason A.; Buckman, Karrie A.; Wu, Kongming; Heimpel, George E.; White, Jennifer A.

2013-01-01

Aphids commonly harbor bacterial facultative symbionts that have a variety of effects upon their aphid hosts, including defense against hymenopteran parasitoids and fungal pathogens. The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is infected with the symbiont Arsenophonus sp., which has an unknown role in its aphid host. Our research goals were to document the infection frequency and diversity of the symbiont in field-collected soybean aphids, and to determine whether Arsenophonus is defending soybean aphid against natural enemies. We performed diagnostic PCR and sequenced four Arsenophonus genes in soybean aphids from their native and introduced range to estimate infection frequency and genetic diversity, and found that Arsenophonus infection is highly prevalent and genetically uniform. To evaluate the defensive role of Arsenophonus, we cured two aphid genotypes of their natural Arsenophonus infection through ampicillin microinjection, resulting in infected and uninfected isolines within the same genetic background. These isolines were subjected to parasitoid assays using a recently introduced biological control agent, Binodoxys communis [Braconidae], a naturally recruited parasitoid, Aphelinus certus [Aphelinidae], and a commercially available biological control agent, Aphidius colemani [Braconidae]. We also assayed the effect of the common aphid fungal pathogen, Pandora neoaphidis (Remaudiere & Hennebert) Humber (Entomophthorales: Entomophthoraceae), on the same aphid isolines. We did not find differences in successful parasitism for any of the parasitoid species, nor did we find differences in P. neoaphidis infection between our treatments. Our conclusion is that Arsenophonus does not defend its soybean aphid host against these major parasitoid and fungal natural enemies. PMID:23614027

Biotechnological Production of Inducible Defense-Related Proteins in Edible Radish (Raphanus Sativus) Found in Nepal

PubMed Central

Khanal, Praval; Karmacharya, Anil; Sharma, Shishir; Nepal, Ashwini K.; Shrestha, Kanti

2014-01-01

Background: Fungal infection in plant leads to use of many hazardous antifungal chemicals. Alternative to these chemicals, defense related antifungal proteins can be used in case of fungal diseases. Aims: An experiment was done in two varieties of edible radish (Raphanus sativus var. Pyuthane Raato and Raphanus sativus var. all season) with aims to produce defense protein within the plant, to identify and perform molecular characterization of those antifungal proteins. The next aim was to compare the antifungal property of those proteins with commercially available synthetic pesticides. Methods: Both varieties of radish were infected with fungi (Alternaria alternata and Fusarium oxysporum). Protein samples were isolated from leaves following the standard protocol as described for β-glucuronidase (GUS) assay and were run along with the standard protein marker of 10-250kDa in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to identify and molecularly characterize them. Results: An additional band in the range of 37-50kDa was observed in the fungal infected samples, which was not seen on uninfected samples. The antifungal assay was carried out for every sample in 96 wells microtitre plate. The extracted protein samples from fungal inoculated plants showed the significant inhibition of fungal growth compared to other samples. On the basis of molecular weight and their antifungal properties, the protein samples from the fungal infected plant were found to be PR2 (Glucanase) and PR3 (Chitinase). Conclusion: Defense related proteins were successfully produced in two varieties of radish found in Nepal. The use of such biologically produced proteins may reduce the use of biologically harmful synthetic pesticides. PMID:24596739

Aspergillus fumigatus carrying TR34/L98H resistance allele causing complicated suppurative otitis media in Tanzania: Call for improved diagnosis of fungi in sub-Saharan Africa.

PubMed

Mushi, Martha F; Buname, Gustave; Bader, Oliver; Groß, Uwe; Mshana, Stephen E

2016-09-02

Suppurative otitis media (SOM) is a major public health concern worldwide and is associated with increased morbidity. Cases of fungal suppurative otitis media were studied to establish the effect of fungi in otitis media. Ear swabs from 410 patients were collected aseptically using sterile cotton swabs from discharging ear through perforated tympanic membrane. Swabs were subjected to microscopic and culture investigations. The species of fungal growing on Sabouraud's agar were identified using MALDI-TOF MS. For moulds broth micro dilution method following EUCAST guidelines was employed to determine susceptibility patterns against itraconazole, voriconazole and posaconazole. A total of 44 (10.74 %) cases with positive fungal culture growth were studied. The median age of patients with fungal infection was 29.5 (IQR 16-43) years. Of 44 patients; 35 (79.6 %) had pure growth of one type of fungal. Candida albicans was the most common fungus isolated (n = 13; 29.6 %) followed by Aspergillus versicolor (n = 8; 18.2 %). A total of 7 (15.9 %) patients had disease complication at time of enrollment; of them 6 (13.6 %) had hearing loss. On follow up 7 (15.9 %) had poor treatment outcome. All five Aspergillus fumigatus strains resistant itraconazole with reduced susceptibility to voriconazole and posaconazole carried carrying TR34/L98H resistance allele. In addition, all Penicillium citrinum isolates were resistant to voriconazole while all Penicillium sumatrense were resistant to both itraconazole and voriconazole. There were non-significant association of poor treatment outcome and female gender, being HIV positive and being infected with moulds. Fungal infections play a significant role in SOM pathology in our setting. Diagnosis of fungal infections in developing countries should be improved so that appropriate management can be initiated on time to prevent associated complications.

Caspofungin in the treatment of invasive fungal infections.

PubMed

Keady, Simon; Thacker, Meera

2006-02-01

Caspofungin is a member of a new class of antifungals called Echinocandins and is the first to have marketing authorisation in the United Kingdom. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of caspofungin. The article also discusses the warnings and precautions associated with the use of this drug. Caspofungin is an effective treatment option in the management of fungal infections.

Fungal infection in Latin American countries.

PubMed

Rios-Fabra, A; Moreno, A R; Istúriz, R E

1994-03-01

Fungal infections remain a frequent health problem in Latin American countries. Although these diseases exhibit an extraordinary heterogeneity, they have certain features in common. Most patients belong to low socioeconomic groups and live in rural areas. This article presents a general view of the most prevalent subcutaneous mycoses, with emphasis on epidemiology, clinical manifestations, laboratory diagnosis, and treatment options in the developing countries of Latin America.

Experimental Infection of Snakes with Ophidiomyces ophiodiicola Causes Pathological Changes That Typify Snake Fungal Disease.

PubMed

Lorch, Jeffrey M; Lankton, Julia; Werner, Katrien; Falendysz, Elizabeth A; McCurley, Kevin; Blehert, David S

2015-11-17

Snake fungal disease (SFD) is an emerging skin infection of wild snakes in eastern North America. The fungus Ophidiomyces ophiodiicola is frequently associated with the skin lesions that are characteristic of SFD, but a causal relationship between the fungus and the disease has not been established. We experimentally infected captive-bred corn snakes (Pantherophis guttatus) in the laboratory with pure cultures of O. ophiodiicola. All snakes in the infected group (n = 8) developed gross and microscopic lesions identical to those observed in wild snakes with SFD; snakes in the control group (n = 7) did not develop skin infections. Furthermore, the same strain of O. ophiodiicola used to inoculate snakes was recovered from lesions of all animals in the infected group, but no fungi were isolated from individuals in the control group. Monitoring progression of lesions throughout the experiment captured a range of presentations of SFD that have been described in wild snakes. The host response to the infection included marked recruitment of granulocytes to sites of fungal invasion, increased frequency of molting, and abnormal behaviors, such as anorexia and resting in conspicuous areas of enclosures. While these responses may help snakes to fight infection, they could also impact host fitness and may contribute to mortality in wild snakes with chronic O. ophiodiicola infection. This work provides a basis for understanding the pathogenicity of O. ophiodiicola and the ecology of SFD by using a model system that incorporates a host species that is easy to procure and maintain in the laboratory. Skin infections in snakes, referred to as snake fungal disease (SFD), have been reported with increasing frequency in wild snakes in the eastern United States. While most of these infections are associated with the fungus Ophidiomyces ophiodiicola, there has been no conclusive evidence to implicate this fungus as a primary pathogen. Furthermore, it is not understood why the infections affect different host populations differently. Our experiment demonstrates that O. ophiodiicola is the causative agent of SFD and can elicit pathological changes that likely impact fitness of wild snakes. This information, and the laboratory model we describe, will be essential in addressing unresolved questions regarding disease ecology and outcomes of O. ophiodiicola infection and helping to conserve snake populations threatened by the disease. The SFD model of infection also offers utility for exploring larger concepts related to comparative fungal virulence, host response, and host-pathogen evolution. Copyright © 2015 Lorch et al.

Burden of serious fungal infections in Ukraine.

PubMed

Osmanov, Ali; Denning, David W

2015-10-01

Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually. © 2015 Blackwell Verlag GmbH.

Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death.

PubMed

Shah, Anand; Kannambath, Shichina; Herbst, Susanne; Rogers, Andrew; Soresi, Simona; Carby, Martin; Reed, Anna; Mostowy, Serge; Fisher, Matthew C; Shaunak, Sunil; Armstrong-James, Darius P

2016-11-01

Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape. These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.

Donor-to-host transmission of bacterial and fungal infections in lung transplantation.

PubMed

Ruiz, I; Gavaldà, J; Monforte, V; Len, O; Román, A; Bravo, C; Ferrer, A; Tenorio, L; Román, F; Maestre, J; Molina, I; Morell, F; Pahissa, A

2006-01-01

The purpose of this study was to evaluate the incidence and etiology of bacterial and fungal infection or contamination in lung allograft donors and to assess donor-to-host transmission of these infections. Recipients who survived more than 24 h and their respective donors were evaluated. The overall incidence of donor infection was 52% (103 out of 197 donors). Types of donor infection included isolated contamination of preservation fluids (n = 30, 29.1%), graft colonization (n = 65, 63.1%) and bacteremia (n = 8, 7.8%). Donor-to-host transmission of bacterial or fungal infection occurred in 15 lung allograft recipients, 7.6% of lung transplants performed. Among these cases, 2 were due to donor bacteremia and 13 to colonization of the graft. Twenty-five percent of donors with bacteremia and 14.1% of colonized grafts were responsible for transmitting infection. Excluding the five cases without an effective prophylactic regimen, prophylaxis failure occurred in 11 out of 197 procedures (5.58%). Donor-to-host transmission of infection is a frequent event after lung transplantation. Fatal consequences can be avoided with an appropriate prophylactic antibiotic regimen that must be modified according to the microorganisms isolated from cultures of samples obtained from donors, grafts, preservation fluids and recipients.

[Nosocomial infection due to Trichosporon asahii in a critical burned patient].

PubMed

Tamayo Lomas, Luis; Domínguez-Gil González, Marta; Martín Luengo, Ana Isabel; Eiros Bouza, José María; Piqueras Pérez, José María

2015-01-01

Invasive fungal infection is an important cause of morbimortality in patients with severe burns. The advances in burn care therapy have considerably extended the survival of seriously burned patients, exposing them to infectious complications, notably fungal infections, with increased recognition of invasive infections caused by Candida species. However, some opportunistic fungi, like Trichosporon asahii, have emerged as important causes of nosocomial infection. A case of nosocomial infection due to T. asahii in a severely ill burned patient successfully treated with voriconazole is presented. The management of invasive fungal infections in burned patients, from diagnosis to selection of the therapeutic protocol, is often a challenge. Early diagnosis and treatment are associated with a better prognosis. In this case report, current treatment options are discussed, and a review of previously published cases is presented. Due to the difficulty in the diagnosis of invasive mycoses and their high associated mortality rates, it is advisable to keep a high degree of clinical suspicion of trichosporonosis in susceptible patients, including burned patients. The isolation of T. asahii in clinical specimens of this type of host must raise clinical alert, since it may precede an invasive infection. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Study of Pathogens of Fungal Keratitis and the Sensitivity of Pathogenic Fungi to Therapeutic Agents with the Disk Diffusion Method.

PubMed

Wang, Lulu; Wang, Liya; Han, Lei; Yin, Weijing

2015-01-01

To identify the causative fungi of fungal keratitis, test their susceptibility to antifungal agents with the disk diffusion method and study the relationship between the organisms, the inhibition zones and the clinical outcomes. 535 patients with fungal keratitis in one eye were included in this study. Pathogenic fungi were isolated by corneal scraping, identified by fungal cultivation and subjected to drug sensitivity tests conducted with the disk diffusion method. The patients were treated initially with voriconazole, terbinafine and natamycin eye drops for one week. Further treatment continued using the most effective drug according to the drug sensitivity results. The patients were followed up every week until three months after cured. The inhibition zones of fungi cultured with voriconazole, terbinafine and natamycin were compared. The relationship between inhibition zones and organism, organism and treatment results measure, and each treatment results measure and inhibition zones were evaluated. Of 535 patients, 53.84%, 19.25% and 26.91% were infected with Aspergillus, Fusarium and other fungi, respectively. Keratitis patients infected with Aspergillus keratitis had the worst outcome. The size of the inhibition zones of Aspergillus spp., Fusarium spp. and other fungal genera differed significantly in response to voriconazole, terbinafine and natamycin. The inhibition zone associated with natamycin correlated significantly with the clinical outcome of fungal keratitis (OR = 0.925), but no other such correlations were found for the other drugs tested. Aspergillus and Fusarium were the predominant pathogenic genera causing fungal keratitis in our patients. Among the causative fungi, infections due to Aspergillus spp. were associated with the worst outcomes. The inhibition zones of fungal isolates in response to natamycin significantly correlated with the treatment outcomes of keratitis. Specifically, the smaller the natamycin inhibition zone, the lower the probability that the fungal keratitis had been eliminated.

Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis.

PubMed

Wan, Qiquan; Liu, Huanmiao; Ye, Shaojun; Ye, Qifa

2017-08-03

BACKGROUND We aimed to investigate blood and urine cultures of donated after cardiac death (DCD) donors and report the cases of confirmed (proven/probable) transmission of bacterial or fungal infection from donors to kidney recipients. MATERIAL AND METHODS Seventy-eight DCD donors between 2010 and 2016 were included. Sixty-one DCD donors underwent blood cultures and 22 episodes of bacteremias developed in 18 donors. Forty-three donors underwent urine cultures and 14 donors experienced 17 episodes of urinary infections. RESULTS Seven of 154 (4.5%) kidney recipients developed confirmed donor-derived bacterial or fungal infections. Inappropriate use of antibiotics in donor was a risk factor for donor-derived infection (p=0.048). The use of FK506 was more frequent in recipients without donor-derived infection than those with donor-derived infection (p=0.033). Recipients with donor-derived infection were associated with higher mortality and graft loss (42.9% and 28.6%, respectively), when compared with those without donor-derived infection (4.8% each). Three kidney recipients with donor-derived infection died; one death was due to multi-organ failure caused by Candida albicans, and two were related to rupture of the renal artery; two of them did not receive appropriate antimicrobial therapy after infection. CONCLUSIONS Our kidney recipients showed high occurrence rates of donor-derived infection. Recipients with donor-derived infection were associated with higher mortality and graft loss than those without donor-derived infection. The majority of recipients with donor-derived infection who died did not receive appropriate antimicrobial therapy after infection.

Operative treatment of early infection after internal fixation of limb fractures (exclusive of severe open fractures).

PubMed

Bonnevialle, P

2017-02-01

Early infection after open reduction and internal fixation (ORIF) of a limb bone is defined as bacteriologically documented, deep and/or superficial surgical-site infection (SSI) diagnosed within 6months after the surgical procedure. This interval is arbitrarily considered sufficient to obtain fracture healing. The treatment of early infection after ORIF should be decided by a multidisciplinary team. The principles are the same as for revision arthroplasty. Superficial SSIs should be differentiated from deep SSIs, based on the results of bacteriological specimens collected using flawless technique. A turning point in the local microbial ecology occurs around the third or fourth week, when a biofilm develops around metallic implants. This biofilm protects the bacteria. The treatment relies on both non-operative and operative measures, which are selected based on the time to occurrence of the infection, condition of the soft tissues, and stage of bone healing. Both the surgical strategy and the antibiotic regimen should be determined during a multidisciplinary discussion. When treating superficial SSIs after ORIF, soft-tissue management is the main challenge. The treatment differs according to whether the hardware is covered or exposed. Defects in the skin and/or fascia can be managed using reliable reconstructive surgery techniques, either immediately or after a brief period of vacuum-assisted closure. In deep SSIs, deciding whether to leave or to remove the hardware is difficult. If the hardware is removed, the fracture site can be stabilised provisionally using either external fixation or a cement rod. Once infection control is achieved, several measures can be taken to stimulate bone healing before the end of the classical 6-month interval. If the hardware was removed, then internal fixation must be performed once the infection is eradicated. Copyright © 2016. Published by Elsevier Masson SAS.

Cereal fungal infection, mycotoxins, and lactic acid bacteria mediated bioprotection: from crop farming to cereal products.

PubMed

Oliveira, Pedro M; Zannini, Emanuele; Arendt, Elke K

2014-02-01

Lactic acid bacteria (LAB) metabolites are a reliable alternative for reducing fungal infections pre-/post-harvest with additional advantages for cereal-base products which convene the food market's trend. Grain industrial use is in expansion owing to its applicability in generating functional food. The food market is directed towards functional natural food with clear health benefits for the consumer in detriment to chemical additives. The food market chain is becoming broader and more complex, which presents an ever-growing fungal threat. Toxigenic and spoilage fungi are responsible for numerous diseases and economic losses. Cereal infections may occur in the field or post-processing, along the food chain. Consequently, the investigation of LAB metabolites with antifungal activity has gained prominence in the scientific research community. LAB bioprotection retards the development of fungal diseases in the field and inhibit pathogens and spoilage fungi in food products. In addition to the health safety improvement, LAB metabolites also enhance shelf-life, organoleptic and texture qualities of cereal-base foods. This review presents an overview of the fungal impact through the cereal food chain leading to investigation on LAB antifungal compounds. Applicability of LAB in plant protection and cereal industry is discussed. Specific case studies include Fusarium head blight, malting and baking. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Prevalence of fungal infections detected from biopsies and autopsies in the past 11 years at the University Hospital Joan XXIII in Tarragona, Spain].

PubMed

García-Fontgivell, Joan Francesc; Mayayo Artal, Emilio

2006-12-01

Infectious diseases caused by fungal pathogens have increased in the past 10 years. More than 300 pathogenic fungal species have been incriminated as the etiologic agents. We carried out a retrospective study (1994-2004) to evaluate the prevalence of mycoses at the University Hospital Joan XXIII (330 beds). This report found 0.24% of the studied cases (78,310 biopsies and 753 autopsies) were diagnosed as fungal infections (0.21% of the total studied biopsy and 4.25% of the whole autopsies). Skin and mucose were involved in 66% of cases, followed by other less affected anatomical areas. 61% of studied cases were caused by Candida spp (the most frequent in our environment), followed by Aspergillus spp (10%) and the Zygomycetes (5%). The most important underlying illness was obstructive chronic pulmonary disease followed by diabetes and AIDS. The incidence of mycoses increased with the patient's age, especially those patients in their 80s. Antifungal management improved the clinical outcome of the patient but predisposing factors are crucial for diagnosis. Systemic mycoses have poor prognosis with 91% of fatal outcome. Thus, it is important to perform a rapid diagnosis of the fungal infections a diagnostic area in which pathology could play a major role.

A polymicrobial fungal outbreak in a regional burn center after Hurricane Sandy.

PubMed

Sood, Geeta; Vaidya, Dhananjay; Dam, Lisa; Grubb, Lisa M; Zenilman, Jonathan; Krout, Kelly; Khouri-Stevens, Zeina; Bennett, Richard; Blanding, Renee; Riedel, Stefan; Milner, Stephen; Price, Leigh Ann; Perl, Trish M

2018-03-30

To describe a polymicrobial fungal outbreak after Hurricane Sandy. An observational concurrent outbreak investigation and retrospective descriptive review. A regional burn intensive care unit that serves the greater Baltimore area, admitting 350-450 burn patients annually. Patients with burn injuries and significant dermatologic diseases such as toxic epidermal necrolysis who were admitted to the burn intensive care unit. An outbreak investigation and a retrospective review of all patients with non-candida fungal isolates from 2009-2016 were performed. A polymicrobial fungal outbreak in burn patients was temporally associated with Hurricane Sandy and associated with air and water permeations in the hospital facility. The outbreak abated after changes to facility design. Our results suggest a possible association between severe weather events like hurricanes and nosocomial fungal outbreaks. This report adds to the emerging literature on the effect of severe weather on healthcare-associated infections. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

[Quantitative assessment of fungal risk in the case of construction works in healthcare establishments: Proposed indicators for the determination of the impact of management precautions on the risk of fungal infection].

PubMed

Gangneux, J-P; Adjidé, C-C; Bernard, L; Botterel, F; Carel, A; Castel, O; Derouin, F; Hoarau, G; Labussière, H; Lafaurie, M; Millon, L; Pottecher, B; Thiebaut, A; Turco, M; Baron, R

2012-03-01

Construction works in healthcare establishments produce airborne fungal spores and considerably increase the risk of exposure of immunosuppressed patients. It is necessary to reinforce protective measures, or even to implement specific precautions, during this critical phase. The aim of these precautions is to protect both those areas, which are susceptible to dust, and patients at risk of a fungal infection particularly invasive aspergillosis. When construction works are planned in healthcare establishments, the first step consists in the characterisation of the environmental fungal risk and the second one in proposing risk management methods. It is then essential to establish impact indicators in order to evaluate the risk management precautions applied. The working group promoted by the French societies of medical mycology and hospital hygiene (SFMM & SF2H) details here both environmental and epidemiological impact indicators that can be used. Copyright © 2012. Published by Elsevier SAS.

Sporotrichosis in cats: ABCD guidelines on prevention and management.

PubMed

Lloret, Albert; Hartmann, Katrin; Pennisi, Maria Grazia; Ferrer, Lluis; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hosie, Margaret J; Lutz, Hans; Marsilio, Fulvio; Möstl, Karin; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Horzinek, Marian C

2013-07-01

Sporotrichosis is an important subcutaneous fungal infection of humans and animals in some endemic tropical and subtropical areas. Among domestic species, cats are the most frequently infected. The primary mode of transmission is traumatic inoculation of fungal conidia from plants and soil. Contact with infected cats is the major mode of transmission to humans, especially in endemic areas like Brazil, where a large epidemic has occurred in the past decade. Most cases in cats are cutaneous, presenting as multiple ulcerated nodules and draining tracts in the skin. Lymphadenopathy, respiratory signs and systemic dissemination may also occur. Diagnosis is based on fungal detection by cytology and/or histology, and confirmation by culture. Treatment consists of at least 2 months' systemic antifungal therapy, with itraconazole as the first-choice agent. The prognosis is favourable provided there is good owner compliance and adverse drug effects do not occur. Contact with infected cats carries a high zoonotic risk. Cat owners travelling to endemic areas should be warned and advised to keep their cats indoors to prevent infection. Professionals must wear gloves when handling cats with skin nodules and ulcers and dealing with diagnostic samples.

Infections of the head and ocular structures in the horse.

PubMed

Gerard, Mathew P; Wotman, Kathryn L; Komáromy, András M

2006-08-01

Infectious conditions of the equine head are commonly encountered in clinical practice. Pathogenic bacterial, viral, and fungal organisms may localize in the extensive nasal passages, paranasal sinuses, and guttural pouches, creating a range of clinical signs and conditions that can be severe enough to lead to unexpected fatality. Renewed interest in equine dentistry has led to a greater recognition of dental disease that is associated with infection. This article focuses on bacterial and fungal infections of the main anatomic regions of the equine head, where advances in diagnosis and management have been made or consolidated in recent years. It also addresses recent advances made in the area of infectious equine corneal disease, including bacterial, viral, and fungal etiologies. Recent developments in equine recurrent uveitis as it relates to infectious diseases and ocular manifestations of systemic disease are also discussed.

Mononuclear Phagocyte-Mediated Antifungal Immunity: The Role of Chemotactic Receptors and Ligands

PubMed Central

Swamydas, Muthulekha; Break, Timothy J.; Lionakis, Michail S.

2015-01-01

Over the past two decades, fungal infections have emerged as significant causes of morbidity and mortality in patients with hematological malignancies, hematopoietic stem cell or solid organ transplantation and acquired immunodeficiency syndrome. Besides neutrophils and CD4+ T lymphocytes, which have long been known to play an indispensable role in promoting protective antifungal immunity, mononuclear phagocytes are now being increasingly recognized as critical mediators of host defense against fungi. Thus, a recent surge of research studies has focused on understanding the mechanisms by which resident and recruited monocytes, macrophages and dendritic cells accumulate and become activated at the sites of fungal infection. Herein, we critically review how a variety of G-protein coupled chemoattractant receptors and their ligands mediate mononuclear phagocyte recruitment and effector function during infection by the most common human fungal pathogens. PMID:25715741

Eosinophils subvert host resistance to an intracellular pathogen by instigating non-protective IL-4 in CCR2-/- mice.

PubMed

Verma, A H; Bueter, C L; Rothenberg, M E; Deepe, G S

2017-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases; however, their influence on intracellular pathogens is less clear. We previously reported that CCR2 -/- mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated interleukin (IL)-4 response. We sought to identify the cellular source promulgating IL-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2 -/- animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity.

Exploration of Fungal Association From Hard Coral Against Pathogen MDR Staphylococcus haemolyticus

NASA Astrophysics Data System (ADS)

Cristianawati, O.; Radjasa, O. K.; Sabdono, A.; Trianto, A.; Sabdaningsih, A.; Sibero, M. T.; Nuryadi, H.

2017-02-01

Staphylococcus haemolyticus are opportunistic bacteria and as the second leading cause of nosocomial infections. It is a disease causing septicemia, peritonitis, otitis, and urinary tract infections and infections of the eye. It also a phenotype resistant to multiple antibiotics commercial. There is now an urgency to find an alternative antibiotics to combat this bacteria. It has been widely reported that many bioactive marine natural products from marine invertebrate have striking similarities to metabolites of their associated microorganisms including fungi. Hard coral associated microorganisms are among of the most interesting and promising marine natural product sources, which produce with various biological activities. The proposed work focused on the discovery of bioactive compounds and also estimated the phylogenetic diversity from fungal association of hard coral against pathogen MDR Staphylococcus haemolyticus. A total of 32 fungal association, FHP 7 which were isolated from Favia sp. capable of inhibiting the growth MDR. Molecular identification based on 18S rRNA gene sequences revealed that the active fungal association belonged 100% to the members from one of the genera Trichoderma longibrachiatum. Accession Number LC185084.1.

Atmospheric cold plasma jet for plant disease treatment

NASA Astrophysics Data System (ADS)

Zhang, Xianhui; Liu, Dongping; Zhou, Renwu; Song, Ying; Sun, Yue; Zhang, Qi; Niu, Jinhai; Fan, Hongyu; Yang, Si-ze

2014-01-01

This study shows that the atmospheric cold plasma jet is capable of curing the fungus-infected plant leaves and controlling the spread of infection as an attractive tool for plant disease management. The healing effect was significantly dependent on the size of the black spots infected with fungal cells and the leaf age. The leaves with the diameter of black spots of <2 mm can completely recover from the fungus-infected state. The plasma-generated species passing through the microns-sized stomas in a leaf can weaken the function of the oil vacuoles and cell membrane of fungal cells, resulting in plasma-induced inactivation.

Successful Treatment of Disseminated Cryptococcal Infection in a Pediatric Acute Lymphoblastic Leukemia Patient During Induction

PubMed Central

Heath, Jessica L.; Yin, Dwight E.; Wechsler, Daniel S.; Turner, David A.

2015-01-01

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between anti-fungal and anti-neoplastic therapy. This balance is particularly important early in the course of leukemia, since both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy. PMID:22258349

Antimicrobial blue light therapy for Candida albicans burn infection in mice

NASA Astrophysics Data System (ADS)

Zhang, Yunsong; Wang, Yucheng; Murray, Clinton K.; Hamblin, Michael R.; Gu, Ying; Dai, Tianhong

2015-05-01

In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015).

Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host to study fungal infections.

PubMed

de Souza, Patrícia Canteri; Morey, Alexandre Tadachi; Castanheira, Gabriel Marcondes; Bocate, Karla Paiva; Panagio, Luciano Aparecido; Ito, Fabio Augusto; Furlaneto, Márcia Cristina; Yamada-Ogatta, Sueli Fumie; Costa, Idessânia Nazareth; Mora-Montes, Hector Manuel; Almeida, Ricardo Sergio

2015-11-01

Models of host–pathogen interactions are crucial for the analysis of microbial pathogenesis. In this context, invertebrate hosts, including Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode) and Galleria mellonella (moth), have been used to study the pathogenesis of fungi and bacteria. Each of these organisms offers distinct benefits in elucidating host–pathogen interactions. In this study,we present a newinvertebrate infection model to study fungal infections: the Tenebrio molitor (beetle) larvae. Here we performed T. molitor larvae infection with one of two important fungal human pathogens, Candida albicans or Cryptococcus neoformans, and analyzed survival curves and larva infected tissues.We showed that increasing concentrations of inoculum of both fungi resulted in increased mortality rates, demonstrating the efficiency of the method to evaluate the virulence of pathogenic yeasts. Additionally, following 12 h post-infection, C. albicans formsmycelia, spreading its hyphae through the larva tissue,whilst GMS stain enabled the visualization of C. neoformans yeast and theirmelanin capsule. These larvae are easier to cultivate in the laboratory than G. mellonella larvae, and offer the same benefits. Therefore, this insect model could be a useful alternative tool to screen clinical pathogenic yeast strainswith distinct virulence traits or different mutant strains.

Prospects for the development of fungal vaccines.

PubMed

Deepe, G S

1997-10-01

In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens.

α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.

PubMed

Uryu, Hidetaka; Hashimoto, Daigo; Kato, Koji; Hayase, Eiko; Matsuoka, Satomi; Ogasawara, Reiki; Takahashi, Shuichiro; Maeda, Yoshinobu; Iwasaki, Hiromi; Miyamoto, Toshihiro; Saijo, Shinobu; Iwakura, Yoichiro; Hill, Geoffrey R; Akashi, Koichi; Teshima, Takanori

2015-05-07

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT. © 2015 by The American Society of Hematology.

Efficacy of ferulic acid encapsulated chitosan nanoparticles against Candida albicans biofilm.

PubMed

Panwar, Richa; Pemmaraju, Suma C; Sharma, Asvene K; Pruthi, Vikas

2016-06-01

Candida albicans, an opportunistic fungal pathogen is a major causative agent of superficial to systemic life-threating biofilm infections on indwelling medical devices. These biofilms acts as double edge swords owing to their resistance towards antibiotics and immunological barriers. To overcome this threat ferulic acid encapsulated chitosan nanoparticles (FA-CSNPs) were formulated to assess its efficacy as an antibiofilm agent against C. albicans. These FA-CSNPs were synthesized using ionotropic gelation method and observed through field emission scanning electron microscopy (FESEM) and fluorescent microscopy. Assessment of successful encapsulation and stability of ferulic acid into chitosan nanoparticles was made using Fourier transform infrared spectrum (FTIR), (1)H NMR and thermal analyses. Synthesized FA-CSNPs, were found to be cytocompatible, when tested using Human Embryonic Kidney (HEK-293) cell lines. XTT assay revealed that FA-CSNPs reduced the cell metabolic activity of C. albicans upto 22.5% as compared to native ferulic acid (63%) and unloaded CSNPs (88%) after 24 h incubation. Disruption of C. albicans biofilm architecture was visualized by FESEM. Results highlighted the potential of FA-CSNPs to be used as an effective alternative to the conventional antifungal therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary investigation tests of novel antifungal topical aerosol

PubMed Central

Kapadia, Monali M.; Solanki, S. T.; Parmar, V.; Thosar, M. M.; Pancholi, S. S.

2012-01-01

Spray formulation can minimize pain and irritation experience during the application of conventional dosage forms. Econazole Nitrate is an active ingredient of the aerosol concentrate to be used for twice-daily application because of its long durability in the superficial layers of the fungal infected skin. The aim of this study is preliminary investigation of Econazole Nitrate spray by varying the concentrations of different constituents of the spray. The ratios of Propylene glycol (PG) and isopropyl myristate (IPM) were selected as independent variables in 22 full factorial designs, keeping the concentration of solvent, co-solvent and propellant LPG constant. Aerosol also contained Ethanol as solvent and Isopropyl alcohol as co-solvent. All ingredients of the aerosol were packaged in an aluminum container fitted with continuous-spray valves. Physical properties evaluated for the Econazole Nitrate spray included delivery rate, delivery amount, pressure, minimum fill, leakage, flammability, spray patterns, particle image and plume angle. Glass containers were used to study incompatibility between concentrate and propellant due to the ease of visible inspection. Isopropyl myristate at lower concentrate showed turbidity, while at high concentration it met the requirements for aerosol and produced Econazole Nitrate spray with expected characteristics. PMID:23066214

Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

PubMed

Blumstein, Gideon W; Parsa, Arya; Park, Anthony K; McDowell, Beverly L P; Arroyo-Mendoza, Melissa; Girguis, Marie; Adler-Moore, Jill P; Olson, Jon; Buckley, Nancy E

2014-01-01

Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5) C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×10(4) C. albicans on day 2, followed by a higher challenge with 5×10(5) C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.

Invasive fungal infections in endogenous Cushing's syndrome

PubMed Central

Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

2010-01-01

Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

Healthcare-associated outbreaks due to Mucorales and other uncommon fungi.

PubMed

Davoudi, Setareh; Graviss, Linda S; Kontoyiannis, Dimitrios P

2015-07-01

Healthcare-associated outbreaks of fungal infections, especially with uncommon and emerging fungi, have become more frequent in the past decade. Here, we reviewed the history and definition of healthcare-associated outbreaks of uncommon fungal infections and discussed the principles of investigating, containing and treatment of these outbreaks. In case of these uncommon diseases, occurrence of two or more cases in a short period is considered as an outbreak. Contaminated medical devices and hospital environment are the major sources of these outbreaks. Care must be taken to differentiate a real infection from colonization or contamination. Defining and identifying cases, describing epidemiologic feature of cases, finding and controlling the source of the outbreak, treating patients, and managing asymptomatic exposed patients are main steps for outbreak elimination. These fungal outbreaks are not only difficult to detect but also hard to treat. Early initiation of appropriate antifungal therapy is strongly associated with improved outcomes in infected patients. Choice of antifungal drugs should be made based on spectrum, pharmacodynamic and pharmacokinetic characteristics and adverse effects of available drugs. Combination antifungal therapy and surgical intervention may be also helpful in selected cases. A multidisciplinary approach and close collaboration between all key partners are necessary for successful control of fungal outbreaks. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Emerging issues, challenges, and changing epidemiology of fungal disease outbreaks.

PubMed

Benedict, Kaitlin; Richardson, Malcolm; Vallabhaneni, Snigdha; Jackson, Brendan R; Chiller, Tom

2017-12-01

Several high-profile outbreaks have drawn attention to invasive fungal infections (IFIs) as an increasingly important public health problem. IFI outbreaks are caused by many different fungal pathogens and are associated with numerous settings and sources. In the community, IFI outbreaks often occur among people without predisposing medical conditions and are frequently precipitated by environmental disruption. Health-care-associated IFI outbreaks have been linked to suboptimal hospital environmental conditions, transmission via health-care workers' hands, contaminated medical products, and transplantation of infected organs. Outbreak investigations provide important insights into the epidemiology of IFIs, uncover risk factors for infection, and identify opportunities for preventing similar events in the future. Well recognised challenges with IFI outbreak recognition, response, and prevention include the need for improved rapid diagnostic methods, the absence of routine surveillance for most IFIs, adherence to infection control practices, and health-care provider awareness. Additionally, IFI outbreak investigations have revealed several emerging issues, including new populations at risk because of travel or relocation, occupation, or immunosuppression; fungal pathogens appearing in geographical areas in which they have not been previously recognised; and contaminated compounded medications. This report highlights notable IFI outbreaks in the past decade, with an emphasis on these emerging challenges in the USA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Host-induced gene silencing of cytochrome P450 lanosterol C14α-demethylase–encoding genes confers strong resistance to Fusarium species

PubMed Central

Koch, Aline; Kumar, Neelendra; Weber, Lennart; Keller, Harald; Imani, Jafargholi; Kogel, Karl-Heinz

2013-01-01

Head blight, which is caused by mycotoxin-producing fungi of the genus Fusarium, is an economically important crop disease. We assessed the potential of host-induced gene silencing targeting the fungal cytochrome P450 lanosterol C-14α-demethylase (CYP51) genes, which are essential for ergosterol biosynthesis, to restrict fungal infection. In axenic cultures of Fusarium graminearum, in vitro feeding of CYP3RNA, a 791-nt double-stranded (ds)RNA complementary to CYP51A, CYP51B, and CYP51C, resulted in growth inhibition [half-maximum growth inhibition (IC50) = 1.2 nM] as well as altered fungal morphology, similar to that observed after treatment with the azole fungicide tebuconazole, for which the CYP51 enzyme is a target. Expression of the same dsRNA in Arabidopsis and barley rendered susceptible plants highly resistant to fungal infection. Microscopic analysis revealed that mycelium formation on CYP3RNA-expressing leaves was restricted to the inoculation sites, and that inoculated barley caryopses were virtually free of fungal hyphae. This inhibition of fungal growth correlated with in planta production of siRNAs corresponding to the targeted CYP51 sequences, as well as highly efficient silencing of the fungal CYP51 genes. The high efficiency of fungal inhibition suggests that host-induced gene-silencing targeting of the CYP51 genes is an alternative to chemical treatments for the control of devastating fungal diseases. PMID:24218613

New strategy for rapid diagnosis and characterization of fungal infections: the example of corneal scrapings.

PubMed

Goldschmidt, Pablo; Degorge, Sandrine; Che Sarria, Patricia; Benallaoua, Djida; Semoun, Oudy; Borderie, Vincent; Laroche, Laurent; Chaumeil, Christine

2012-01-01

The prognosis of people infected with Fungi especially immunocompromised depends on rapid and accurate diagnosis to capitalize on time administration of specific treatments. However, cultures produce false negative results and nucleic-acid amplification techniques require complex post-amplification procedures to differentiate relevant fungal types. The objective of this work was to develop a new diagnostic strategy based on real-time polymerase-chain reaction high-resolution melting analysis (PCR-HRM) that a) detects yeasts and filamentous Fungi, b) differentiates yeasts from filamentous Fungi, and c) discriminates among relevant species of yeasts. PCR-HRM detection limits and specificity were assessed with a) isolated strains; b) human blood samples experimentally infected with Fungi; c) blood experimentally infected with other infectious agents; d) corneal scrapings from patients with suspected fungal keratitis (culture positive and negative) and e) scrapings from patients with suspected bacterial, viral or Acanthamoeba infections. The DNAs were extracted and mixed with primers diluted in the MeltDoctor® HRM Master Mix in 2 tubes, the first for yeasts, containing the forward primer CandUn (5'CATGCCTGTTTGAGCGTC) and the reverse primer FungUn (5'TCCTCCGCTT ATTGATATGCT) and the second for filamentous Fungi, containing the forward primer FilamUn (5'TGCCTGTCCGAGCGTCAT) and FungUn. Molecular probes were not necessary. The yields of DNA extraction and the PCR inhibitors were systematically monitored. PCR-HRM detected 0.1 Colony Forming Units (CFU)/µl of yeasts and filamentous Fungi, differentiated filamentous Fungi from yeasts and discriminated among relevant species of yeasts. PCR-HRM performances were higher than haemoculture and sensitivity and specificity was 100% for culture positive samples, detecting and characterizing Fungi in 7 out 10 culture negative suspected fungal keratitis. PCR-HRM appears as a new, sensitive, specific and inexpensive test that detects Fungi and differentiates filamentous Fungi from yeasts. It allows direct fungal detection from clinical samples and experimentally infected blood in less than 2.30 h after DNA extraction.

Curvularia keratitis.

PubMed Central

Wilhelmus, K R; Jones, D B

2001-01-01

PURPOSE: To determine the risk factors and clinical signs of Curvularia keratitis and to evaluate the management and outcome of this corneal phaeohyphomycosis. METHODS: We reviewed clinical and laboratory records from 1970 to 1999 to identify patients treated at our institution for culture-proven Curvularia keratitis. Descriptive statistics and regression models were used to identify variables associated with the length of antifungal therapy and with visual outcome. In vitro susceptibilities were compared to the clinical results obtained with topical natamycin. RESULTS: During the 30-year period, our laboratory isolated and identified Curvularia from 43 patients with keratitis, of whom 32 individuals were treated and followed up at our institute and whose data were analyzed. Trauma, usually with plants or dirt, was the risk factor in one half; and 69% occurred during the hot, humid summer months along the US Gulf Coast. Presenting signs varied from superficial, feathery infiltrates of the central cornea to suppurative ulceration of the peripheral cornea. A hypopyon was unusual, occurring in only 4 (12%) of the eyes but indicated a significantly (P = .01) increased risk of subsequent complications. The sensitivity of stained smears of corneal scrapings was 78%. Curvularia could be detected by a panfungal polymerase chain reaction. Fungi were detected on blood or chocolate agar at or before the time that growth occurred on Sabouraud agar or in brain-heart infusion in 83% of cases, although colonies appeared only on the fungal media from the remaining 4 sets of specimens. Curvularia was the third most prevalent filamentous fungus among our corneal isolates and the most common dematiaceous mold. Corneal isolates included C senegalensis, C lunata, C pallescens, and C prasadii. All tested isolates were inhibited by 4 micrograms/mL or less of natamycin. Topical natamycin was used for a median duration of 1 month, but a delay in diagnosis beyond 1 week doubled the average length of topical antifungal treatment (P = .005). Visual acuity improved to 20/40 or better in 25 (78%) of the eyes. CONCLUSIONS: Curvularia keratitis typically presented as superficial feathery infiltration, rarely with visible pigmentation, that gradually became focally suppurative. Smears of corneal scrapings often disclosed hyphae, and culture media showed dematiaceous fungal growth within 1 week. Natamycin had excellent in vitro activity and led to clinical resolution with good vision in most patients with corneal curvulariosis. Complications requiring surgery were not common but included exophytic inflammatory fungal sequestration, treated by superficial lamellar keratectomy, and corneal perforation, managed by penetrating keratoplasty. PMID:11797300

Proteomic analysis of ripening tomato fruit infected by Botrytis cinerea.

PubMed

Shah, Punit; Powell, Ann L T; Orlando, Ron; Bergmann, Carl; Gutierrez-Sanchez, Gerardo

2012-04-06

Botrytis cinerea, a model necrotrophic fungal pathogen that causes gray mold as it infects different organs on more than 200 plant species, is a significant contributor to postharvest rot in fresh fruit and vegetables, including tomatoes. By describing host and pathogen proteomes simultaneously in infected tissues, the plant proteins that provide resistance and allow susceptibility and the pathogen proteins that promote colonization and facilitate quiescence can be identified. This study characterizes fruit and fungal proteins solubilized in the B. cinerea-tomato interaction using shotgun proteomics. Mature green, red ripe wild type and ripening inhibited (rin) mutant tomato fruit were infected with B. cinerea B05.10, and the fruit and fungal proteomes were identified concurrently 3 days postinfection. One hundred eighty-six tomato proteins were identified in common among red ripe and red ripe-equivalent ripening inhibited (rin) mutant tomato fruit infected by B. cinerea. However, the limited infections by B. cinerea of mature green wild type fruit resulted in 25 and 33% fewer defense-related tomato proteins than in red and rin fruit, respectively. In contrast, the ripening stage of genotype of the fruit infected did not affect the secreted proteomes of B. cinerea. The composition of the collected proteins populations and the putative functions of the identified proteins argue for their role in plant-pathogen interactions.

Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives

PubMed Central

Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

2016-01-01

Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283

Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives.

PubMed

Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

2016-04-01

Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fluconazole Injection

MedlinePlus

... injection is used to treat fungal infections, including yeast infections of the mouth, throat, esophagus (tube leading ... by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become ...

Procalcitonin levels in gram-positive, gram-negative, and fungal bloodstream infections.

PubMed

Leli, Christian; Ferranti, Marta; Moretti, Amedeo; Al Dhahab, Zainab Salim; Cenci, Elio; Mencacci, Antonella

2015-01-01

Procalcitonin (PCT) can discriminate bacterial from viral systemic infections and true bacteremia from contaminated blood cultures. The aim of this study was to evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative, and fungal bloodstream infections. A total of 1,949 samples from patients with suspected bloodstream infections were included in the study. Median PCT value in Gram-negative (13.8 ng/mL, interquartile range (IQR) 3.4-44.1) bacteremias was significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6-7.6) or fungal (0.5 ng/mL, IQR 0.4-1) infections (P < 0.0001). Receiver operating characteristic analysis showed an area under the curve (AUC) for PCT of 0.765 (95% CI 0.725-0.805, P < 0.0001) in discriminating Gram-negatives from Gram-positives at the best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919-0.969, P < 0.0001) in discriminating Gram-negatives from fungi at the best cut-off of 1.6 ng/mL. Additional results showed a significant difference in median PCT values between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1 ng/mL, IQR 5.9-48.5 versus 3.5 ng/mL, IQR 0.8-21.5; P < 0.0001). This study suggests that PCT may be of value to distinguish Gram-negative from Gram-positive and fungal bloodstream infections. Nevertheless, its utility to predict different microorganisms needs to be assessed in further studies.

Candida Biofilms: Threats, Challenges, and Promising Strategies.

PubMed

Cavalheiro, Mafalda; Teixeira, Miguel Cacho

2018-01-01

Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis , and Candida parapsilosis , highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

Introduction of a dermatophyte polymerase chain reaction assay to the diagnostic mycology service in Scotland.

PubMed

Alexander, C L; Shankland, G S; Carman, W; Williams, C

2011-05-01

Dermatophytes are the major cause of superficial mycoses in samples submitted to Clinical Mycology, Glasgow. The most prevalent species is Trichophyton rubrum as identified classically by microscopy and culture. Recent advances in polymerase chain reaction (PCR) technology were examined for the feasibility of introducing a T. rubrum real-time PCR assay into a routine diagnostic service. To improve the diagnostic mycology service by the introduction of a real-time PCR test for T. rubrum. The DNA from 4972 nail and skin samples was obtained using the Qiagen QIAsymphony automated extractor. This DNA was subjected to real-time PCR using T. rubrum-specific primers and a probe. During phase 1 of the study, 862 samples were analysed; 446 of 470 specimens that grew T. rubrum were detected by PCR. Out of 4110 samples analysed during phase 2, 753 T. rubrum infections were diagnosed and reported within 72 h. A total of 3357 samples were negative for a fungal infection by PCR and microscopy; these were also reported within 72 h. A vast reduction in the turnaround times can be achieved using this technique as opposed to classical methods. Samples which are PCR negative but microscopy positive are still subjected to culture. Screening samples for their suitability for PCR prior to processing eliminates the application of PCR for T. rubrum on inappropriate samples such those from the scalp or pityriasis versicolor. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Candida Biofilms: Threats, Challenges, and Promising Strategies

PubMed Central

Cavalheiro, Mafalda; Teixeira, Miguel Cacho

2018-01-01

Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed. PMID:29487851

Biosynthesized silver and gold nanoparticles are potent antimycotics against opportunistic pathogenic yeasts and dermatophytes.

PubMed

Rónavári, Andrea; Igaz, Nóra; Gopisetty, Mohana Krishna; Szerencsés, Bettina; Kovács, Dávid; Papp, Csaba; Vágvölgyi, Csaba; Boros, Imre Miklós; Kónya, Zoltán; Kiricsi, Mónika; Pfeiffer, Ilona

2018-01-01

Epidemiologic observations indicate that the number of systemic fungal infections has increased significantly during the past decades, however in human mycosis, mainly cutaneous infections predominate, generating major public health concerns and providing much of the impetus for current attempts to develop novel and efficient agents against cutaneous mycosis causing species. Innovative, environmentally benign and economic nanotechnology-based approaches have recently emerged utilizing principally biological sources to produce nano-sized structures with unique antimicrobial properties. In line with this, our aim was to generate silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) by biological synthesis and to study the effect of the obtained nanoparticles on cutaneous mycosis causing fungi and on human keratinocytes. Cell-free extract of the red yeast Phaffia rhodozyma proved to be suitable for nanoparticle preparation and the generated AgNPs and AuNPs were characterized by transmission electron microscopy, dynamic light scattering and X-ray powder diffraction. Antifungal studies demonstrated that the biosynthesized silver particles were able to inhibit the growth of several opportunistic Candida or Cryptococcus species and were highly potent against filamentous Microsporum and Trichophyton dermatophytes. Among the tested species only Cryptococcus neoformans was susceptible to both AgNPs and AuNPs. Neither AgNPs nor AuNPs exerted toxicity on human keratinocytes. Our results emphasize the therapeutic potential of such biosynthesized nanoparticles, since their biocompatibility to skin cells and their outstanding antifungal performance can be exploited for topical treatment and prophylaxis of superficial cutaneous mycosis.

Fluconazole and Pregnancy

MedlinePlus

... It is used in the treatment of vaginal yeast infections when topical creams are not effective. A ... the most commonly used dose to treat vaginal yeast infections. It is also used for fungal infections ...

Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis

PubMed Central

Wan, Qiquan; Liu, Huanmiao; Ye, Shaojun; Ye, Qifa

2017-01-01

Background We aimed to investigate blood and urine cultures of donated after cardiac death (DCD) donors and report the cases of confirmed (proven/probable) transmission of bacterial or fungal infection from donors to kidney recipients. Material/Methods Seventy-eight DCD donors between 2010 and 2016 were included. Sixty-one DCD donors underwent blood cultures and 22 episodes of bacteremias developed in 18 donors. Forty-three donors underwent urine cultures and 14 donors experienced 17 episodes of urinary infections. Results Seven of 154 (4.5%) kidney recipients developed confirmed donor-derived bacterial or fungal infections. Inappropriate use of antibiotics in donor was a risk factor for donor-derived infection (p=0.048). The use of FK506 was more frequent in recipients without donor-derived infection than those with donor-derived infection (p=0.033). Recipients with donor-derived infection were associated with higher mortality and graft loss (42.9% and 28.6%, respectively), when compared with those without donor-derived infection (4.8% each). Three kidney recipients with donor-derived infection died; one death was due to multi-organ failure caused by Candida albicans, and two were related to rupture of the renal artery; two of them did not receive appropriate antimicrobial therapy after infection. Conclusions Our kidney recipients showed high occurrence rates of donor-derived infection. Recipients with donor-derived infection were associated with higher mortality and graft loss than those without donor-derived infection. The majority of recipients with donor-derived infection who died did not receive appropriate antimicrobial therapy after infection. PMID:28771455

Ceragenins are active against drug-resistant Candida auris clinical isolates in planktonic and biofilm forms.

PubMed

Hashemi, Marjan M; Rovig, John; Holden, Brett S; Taylor, Maddison F; Weber, Scott; Wilson, John; Hilton, Brian; Zaugg, Aaron L; Ellis, Samuel W; Yost, Connor D; Finnegan, Patrick M; Kistler, Charles K; Berkow, Elizabeth L; Deng, Shenglou; Lockhart, Shawn R; Peterson, Marnie; Savage, Paul B

2018-06-01

Candida auris has emerged as a serious threat to human health. Of particular concern are the resistance profiles of many clinical isolates, with some being resistant to multiple classes of antifungals. Measure susceptibilities of C. auris isolates, in planktonic and biofilm forms, to ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and cream formulations in eradicating fungal infections in tissue explants. A collection of 100 C. auris isolates available at CDC was screened for susceptibility to a lead ceragenin. A smaller collection was used to characterize antifungal activities of other ceragenins against organisms in planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms were observed via microscopy. An ex vivo model of mucosal fungal infection was used to evaluate formulated forms of lead ceragenins. Lead ceragenins displayed activities comparable to those of known antifungal agents against C. auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed. Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins exhibited activity against sessile organisms in biofilms. Gel and cream formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs against established fungal infections in ex vivo mucosal tissues. Ceragenins demonstrated activity against C. auris, suggesting that these compounds warrant further study to determine whether they can be used for topical applications to skin and mucosal tissues for treatment of infections with C. auris and other fungi.

Long-term impact of Ophiostoma novo-ulmi on leaf traits and transpiration of branches in the Dutch elm hybrid ‘Dodoens’

PubMed Central

Plichta, Roman; Urban, Josef; Gebauer, Roman; Dvořák, Miloň; Ďurkovič, Jaroslav

2016-01-01

To better understand the long-term impact of Ophiostoma novo-ulmi Brasier on leaf physiology in ‘Dodoens’, a Dutch elm disease-tolerant hybrid, measurements of leaf area, leaf dry mass, petiole anatomy, petiole hydraulic conductivity, leaf and branch water potential, and branch sap flow were performed 3 years following an initial artificial inoculation. Although fungal hyphae were detected in fully expanded leaves, neither anatomical nor morphological traits were affected, indicating that there was no impact from the fungal hyphae on the leaves during leaf expansion. In contrast, however, infected trees showed both a lower transpiration rate of branches and a lower sap flow density. The long-term persistence of fungal hyphae inside vessels decreased the xylem hydraulic conductivity, but stomatal regulation of transpiration appeared to be unaffected as the leaf water potential in both infected and non-infected trees was similarly driven by the transpirational demands. Regardless of the fungal infection, leaves with a higher leaf mass per area ratio tended to have a higher leaf area-specific conductivity. Smaller leaves had an increased number of conduits with smaller diameters and thicker cell walls. Such a pattern could increase tolerance towards hydraulic dysfunction. Measurements of water potential and theoretical xylem conductivity revealed that petiole anatomy could predict the maximal transpiration rate. Three years following fungal inoculation, phenotypic expressions for the majority of the examined traits revealed a constitutive nature for their possible role in Dutch elm disease tolerance of ‘Dodoens’ trees. PMID:26843210

Sensitization and cross-reactions of dermatophyte and Candida albicans allergens in patients with chronic urticaria.

PubMed

Zhang, Min; Liu, Fang; Liu, Haibo; Shen, Yongnian; Kong, Qingtao; Sang, Hong

2016-10-01

Chronic fungal infections are known to exacerbate allergic symptoms, including those of asthma and chronic urticaria (CU). We applied four prepared fungal antigens of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Candida albicans to examine sensitization to each in subjects with CU and onychomycosis and in healthy subjects, and to evaluate the etiologic role of dermatophytic infection in CU and observe any cross-reactions among these four antigens. Participants were divided into four groups, including those with CU with onychomycosis (experiment group), those with onychomycosis without allergic diseases (control group 1), those with CU without fungal infections (control group 2), and a healthy group (control group 3). In all subjects, skin prick tests with the four fungal antigens were performed. Subjects in the experiment group and control group 1 were also submitted to mycologic investigations. The experiment group showed significantly higher rates of positivity than the three control groups to T. rubrum, E. floccosum, and T. mentagrophytes antigens. Control group 1 showed rates higher than those in control groups 2 and 3; no significant difference emerged between control groups 2 and 3. Positivity to the C. albicans antigen did not differ among the four groups. In control group 1, rates of positivity to the three dermatophytic antigens did not differ significantly but did for C. albicans. Fungal infection seems to be an important determinant of trichophyton hypersensitivity. Cross-reactions among T. mentagrophytes, T. rubrum, and E. floccosum antigens were obvious, but none emerged between the antigens of the three dermatophytes and that of C. albicans. © 2016 The International Society of Dermatology.

Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock-Results of a Combined Clinical and Experimental Investigation.

PubMed

Decker, Sebastian O; Sigl, Annette; Grumaz, Christian; Stevens, Philip; Vainshtein, Yevhen; Zimmermann, Stefan; Weigand, Markus A; Hofer, Stefan; Sohn, Kai; Brenner, Thorsten

2017-08-18

Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of β-d-glucan, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A, and mid-regional proadrenomedullin (MR-proADM) were evaluated in 50 septic patients at six consecutive time points within 28 days after sepsis onset. Furthermore, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% ( n = 11) of patients suffered from a fungal infection. An NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene which is upregulated early after an epithelial infection with Candida spp. In summary, an NGS-based diagnostic approach was able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of MR-proADM and IL-17A. In addition, ADM was identified as an early target gene in response to epithelial infections with Candida spp.

Critical environmental and genotypic factors for Fusarium verticillioides infection, fungal growth and fumonisin contamination in maize grown in northwestern Spain.

PubMed

Cao, Ana; Santiago, Rogelio; Ramos, Antonio J; Souto, Xosé C; Aguín, Olga; Malvar, Rosa Ana; Butrón, Ana

2014-05-02

In northwestern Spain, where weather is rainy and mild throughout the year, Fusarium verticillioides is the most prevalent fungus in kernels and a significant risk of fumonisin contamination has been exposed. In this study, detailed information about environmental and maize genotypic factors affecting F. verticillioides infection, fungal growth and fumonisin content in maize kernels was obtained in order to establish control points to reduce fumonisin contamination. Evaluations were conducted in a total of 36 environments and factorial regression analyses were performed to determine the contribution of each factor to variability among environments, genotypes, and genotype × environment interactions for F. verticillioides infection, fungal growth and fumonisin content. Flowering and kernel drying were the most critical periods throughout the growing season for F. verticillioides infection and fumonisin contamination. Around flowering, wetter and cooler conditions limited F. verticillioides infection and growth, and high temperatures increased fumonisin contents. During kernel drying, increased damaged kernels favored fungal growth, and higher ear damage by corn borers and hard rainfall favored fumonisin accumulation. Later planting dates and especially earlier harvest dates reduced the risk of fumonisin contamination, possibly due to reduced incidence of insects and accumulation of rainfall during the kernel drying period. The use of maize varieties resistant to Sitotroga cerealella, with good husk coverage and non-excessive pericarp thickness could also be useful to reduce fumonisin contamination of maize kernels. Copyright © 2014 Elsevier B.V. All rights reserved.

Annular Lichenoid Dermatitis (of Youth) Immunohistochemical and Serological Evidence for Another Clinical Presentation of Borrelia Infection in Patients of Western Austria.

PubMed

Wilk, Michael; Zelger, Bettina G; Emberger, Michael; Zelger, Bernhard

2017-03-01

Annular lichenoid dermatitis of youth (ALDY) is a more recently described inflammatory disease of the skin of unknown etiology with clinical similarities to morphea. The authors clinically, histopathologically, and immunohistochemically investigated 14 biopsies from 12 patients in western Austria with this disease. There were 6 female and 6 male patients with solitary (n = 7) and multiple lesions (n = 5) affecting the trunk (n = 11), upper arm (n = 2), thigh (n = 1), and calf (n = 1). Clinically, early lesions were erythematous in nature leading to central paleness, scaling, wrinkling, dermal atrophy, slight pigmentation, and telangiectasia later on. Histopathologically, all specimens showed the typical features of ALDY with a superficial lichenoid process with sprinkling of lymphocytes along the basal cell layer and within the epidermis accompanied by mild fibrosis. Pigment incontinence, superficial fibrosis, and dilatation of superficial capillary vessels are prominent features in more advanced stages of disease. Immunohistologically, using a polyclonal antibody against Borrelia, 11/14 specimens revealed spirochetes, either vital (n = 4) or degenerated (n = 7), in close proximity to collagen bundles. Thirteen of 14 specimens in addition showed focal (n = 4) or clustered (n = 9) positivity for CD20 in the papillary dermis. Nine of 12 sera tested for Borrelia with an enzyme-linked immunosorbent assay were positive. Lichen sclerosus et atrophicus and morphea have previously been reported to be possibly related to Borrelia infection. We postulate that a similar relationship to Borrelia infection may be true for ALDY implying that ALDY may be an early superficial stage of morphea.

AWBAT: early clinical experience.

PubMed

Vandenberg, Victoria B

2010-03-15

The purpose of this article is to describe the early clinical experience with AWBAT. Burn patients requiring (1) donor sites or (2) treatment of a superficial burn wound injury were treated. A total of 45 patients with 69 distinct wounds were included. AWBAT-D was evaluated in donor sites and AWBAT-S was evaluated in superficial partial-thickness burns. Days to healing, pain, hematoma/seroma formation, and infection were noted. Ease of application, adherence, transparency, and physical adaptability details were collected. Average period to healing of donor sites treated with AWBAT-D (n=22 patients with n=26 wounds) was 11.2 days, sigma =1.95, with a range of 8-15 days and a median of 11 days. Pain rating at 24 hours was 1.2, sigma =0.43 (n=18) and at 48 hours mean was 1.2, sigma =0.46 (n=15). Average period to healing of superficial burns treated with AWBAT-S (n=15 patients with n=18 wounds) was 8.1 days, sigma =2.48, with a range of 5-13 days and a median of 7 days. Pain rating at 24 hours was 1.5, sigma =0.85 (n=10) and at 48 hours mean was 1.75, sigma =0.89 (n=8). There was zero incidence of hematoma/seroma. No infections were seen. Results indicate that AWBAT was easily applied with good initial adherence. It was noted to be transparent, conformant, and pliable. Early experience demonstrates that AWBAT performs well on donor sites and superficial partial-thickness burns and delivers the desired attributes of a temporary skin substitute including good adherence, infection control, transparency, adapatability, and pain control.

Propionibacterium acnes in shoulder surgery: is loss of hair protective for infection?

PubMed

Hudek, Robert; Sommer, Frank; Abdelkawi, Ayman F; Kerwat, Martina; Müller, Hans-Helge; Gohlke, Frank

2016-06-01

Propionibacterium acnes (P acnes) has been linked to chronic infections in shoulder surgery. It was recently observed during first-time shoulder surgery in healthy patients at a rate between 36% and 56%. Male gender and the anterolateral approach were reported risk factors. Because the skin biology greatly differs, we aimed to correlate skin complaints with P acnes-positive intraoperative cultures from different tissue layer samples in patients undergoing shoulder surgery for the first time. Intraoperative samples (1 skin, 1 superficial, 1 deep tissue, and 1 control sample) from 112 patients (70 men, 42 women; aged 59.2 years) were cultured. The association between the presence of P acnes in the deep or superficial tissue, or both, and 10 items of a validated preoperative questionnaire for skin pathology was explored. The cultures were positive for P acnes in 38.4% (n = 43) of the cases. Skin samples were positive for P acnes in 8% (n = 9), superficial samples were positive in 23% (n = 26), and deep samples were positive in 30% (n = 34). Self-reported "loss of hair" was significantly negatively associated with the presence of P acnes in the superficial or deep tissue sample (P = .00028). Patients who report having "loss of hair" show fewer P acnes-positive cultures in intraoperative tissue samples taken during open shoulder surgery. Whether this subgroup is at a lesser risk for P acnes infections remains to be substantiated. Basic Science Study; Microbiology. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Systematic review of the use of honey as a wound dressing

PubMed Central

Moore, Owen A; Smith, Lesley A; Campbell, Fiona; Seers, Kate; McQuay, Henry J; Moore, R Andrew

2001-01-01

Objective To investigate topical honey in superficial burns and wounds though a systematic review of randomised controlled trials. Data sources Cochrane Library, MEDLINE, EMBASE, PubMed, reference lists and databases were used to seek randomised controlled trials. Seven randomised trials involved superficial burns, partial thickness burns, moderate to severe burns that included full thickness injury, and infected postoperative wounds. Review methods Studies were randomised trials using honey, published papers, with a comparator. Main outcomes were relative benefit and number-needed-to-treat to prevent an outcome relating to wound healing time or infection rate. Results One study in infected postoperative wounds compared honey with antiseptics plus systemic antibiotics. The number needed to treat with honey for good wound healing compared with antiseptic was 2.9 (95% confidence interval 1.7 to 9.7). Five studies in patients with partial thickness or superficial burns involved less than 40% of the body surface. Comparators were polyurethane film, amniotic membrane, potato peel and silver sulphadiazine. The number needed to treat for seven days with honey to produce one patient with a healed burn was 2.6 (2.1 to 3.4) compared with any other treatment and 2.7 (2.0 to 4.1) compared with potato and amniotic membrane. For some or all outcomes honey was superior to all these treatments. Time for healing was significantly shorter for honey than all these treatments. The quality of studies was low. Conclusion Confidence in a conclusion that honey is a useful treatment for superficial wounds or burns is low. There is biological plausibility. PMID:11405898

Mixed Fungal Lung Infection with Aspergillus Fumigatus and Candida Albicans in a Immunocomprimised Patient: Case Report

PubMed Central

Vipparti, Haritha

2014-01-01

The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades. In the immune-compromised host, many fungi, including species of fungi typically considered non-pathogenic, have the potential to cause serious morbidity and mortality. Here we report a rare case of mixed fungal infection of the lung with Candida albicans and Aspergillus fumigatus in a patient on prolonged steroid therapy. PMID:24959447

Immune Cell-Supplemented Human Skin Model for Studying Fungal Infections.

PubMed

Kühbacher, Andreas; Sohn, Kai; Burger-Kentischer, Anke; Rupp, Steffen

2017-01-01

Human skin is a niche for various fungal species which either colonize the surface of this tissue as commensals or, primarily under conditions of immunosuppression, invade the skin and cause infection. Here we present a method for generation of a human in vitro skin model supplemented with immune cells of choice. This model represents a complex yet amenable tool to study molecular mechanisms of host-fungi interactions at human skin.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

PubMed

Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

2013-08-13

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis

PubMed Central

Fazly, Ahmed; Jain, Charu; Dehner, Amie C.; Issi, Luca; Lilly, Elizabeth A.; Ali, Akbar; Cao, Hong; Fidel, Paul L.; P. Rao, Reeta; Kaufman, Paul D.

2013-01-01

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis. PMID:23904484

Virulence-Associated Enzymes of Cryptococcus neoformans

PubMed Central

Almeida, Fausto; Wolf, Julie M.

2015-01-01

Enzymes play key roles in fungal pathogenesis. Manipulation of enzyme expression or activity can significantly alter the infection process, and enzyme expression profiles can be a hallmark of disease. Hence, enzymes are worthy targets for better understanding pathogenesis and identifying new options for combatting fungal infections. Advances in genomics, proteomics, transcriptomics, and mass spectrometry have enabled the identification and characterization of new fungal enzymes. This review focuses on recent developments in the virulence-associated enzymes from Cryptococcus neoformans. The enzymatic suite of C. neoformans has evolved for environmental survival, but several of these enzymes play a dual role in colonizing the mammalian host. We also discuss new therapeutic and diagnostic strategies that could be based on the underlying enzymology. PMID:26453651

Topical treatments for fungal infections of the skin and nails of the foot.

PubMed

Crawford, F; Hollis, S

2007-07-18

Fungal infections of the feet normally occur in the outermost layer of the skin (epidermis). The skin between the toes is a frequent site of infection which can cause pain and itchiness. Fungal infections of the nail (onychomycosis) can affect the entire nail plate. To assess the effects of topical treatments in successfully treating (rate of treatment failure) fungal infections of the skin of the feet and toenails and in preventing recurrence. We searched the Cochrane Skin Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE and EMBASE (from inception to January 2005). We screened the Science Citation Index, BIOSIS, CAB - Health and Healthstar, CINAHL DARE, NHS Economic Evaluation Database and EconLit (March 2005). Bibliographies were searched. Randomised controlled trials (RCTs) using participants who had mycologically diagnosed fungal infections of the skin and nails of the foot. Two authors independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool. Of the 144 identified papers, 67 trials met the inclusion criteria. Placebo-controlled trials yielded the following pooled risk ratios (RR) of treatment failure for skin infections: allylamines RR 0.33 (95% CI 0.24 to 0.44); azoles RR 0.30 (95% CI 0.20 to 0.45); ciclopiroxolamine RR 0.27 (95% CI 0.11 to 0.66); tolnaftate RR 0.19 (95% CI 0.08 to 0.44); butenafine RR 0.33 (95% CI 0.24 to 0.45); undecanoates RR 0.29 (95% CI 0.12 - 0.70). Meta-analysis of 11 trials comparing allylamines and azoles showed a risk ratio of treatment failure RR 0.63 (95% CI 0.42 to 0.94) in favour of allylamines. Evidence for the management of topical treatments for infections of the toenails is sparser. There is some evidence that ciclopiroxolamine and butenafine are both effective but they both need to be applied daily for prolonged periods (at least 1 year). The 6 trials of nail infections provided evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective but more research is required. Placebo-controlled trials of allylamines and azoles for athlete's foot consistently produce much higher percentages of cure than placebo. Allylamines cure slightly more infections than azoles and are now available OTC. Further research into the effectiveness of antifungal agents for nail infections is required.

A case of Trichophyton mentagrophytes infection in a fennec fox (Vulpes zerda).

PubMed

Pressanti, Charline; Delverdier, Maxence; Iriart, Xavier; Morcel, Frédérique; Cadiergues, Marie-Christine

2012-10-01

A 2-year-old male fennec fox presented with a 4 month history of nonpruritic, crusty skin lesions on the forehead, the pinnae and the tail tip. Initial investigations, including routine haematology, biochemistry profile, multiple skin scrapings, trichoscopic examination, Wood's lamp examination and fungal culture, failed to reveal any abnormalities. Histopathological examination of a first set of skin biopsies showed an interface dermatitis pattern, with lymphocyte infiltration in the basal layer, a significant lymphocytic exocytosis and occasional apoptotic basal epidermal keratinocytes; periodic acid Schiff stain did not reveal any fungal elements. On further biopsies, there was a pustular neutrophilic dermatitis, with numerous crusts containing high numbers of arthrospores and fungal hyphae. Trichophyton mentagrophytes infection was confirmed on fungal culture and PCR. The fennec fox received oral itraconazole (5 mg/kg once daily for 6 weeks) combined with a miconazole and chlorhexidine shampoo applied on affected areas once weekly, followed with an enilconazole dip. The fox improved dramatically, and a fungal culture performed at 6 weeks was negative. Unfortunately, a few days later the fennec fox developed anorexia, icterus and died. To the authors' knowledge, this is the first report of Trichophyton infection in a fennec fox and, although a postmortem examination was not performed, this is possibly the first report of fatal acute liver failure associated with itraconazole in a canid. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation In Vitro and Influences In Vivo Disease Outcomes.

PubMed

Dhingra, Sourabh; Buckey, Jay C; Cramer, Robert A

2018-03-01

Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, the development of new clinical modalities as stand-alone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we tested the in vitro and in vivo impacts of hyperbaric oxygen (HBO) (100% oxygen, >1 atmosphere absolute [ATA]) on A. fumigatus proliferation and murine IPA outcomes. Our findings indicate that HBO reduces established fungal biofilm proliferation in vitro by over 50%. The effect of HBO under the treatment conditions was transient and fungistatic, with A. fumigatus metabolic activity rebounding within 6 h of HBO treatment being removed. In vivo , daily HBO provides a dose-dependent but modest improvement in murine IPA disease outcomes as measured by survival analysis. Intriguingly, no synergy was observed between subtherapeutic voriconazole or amphotericin B and HBO in vitro or in vivo with daily HBO dosing, though the loss of fungal superoxide dismutase genes enhanced HBO antifungal activity. Further studies are needed to optimize the HBO treatment regimen and better understand the effects of HBO on both the host and the pathogen during a pulmonary invasive fungal infection. Copyright © 2018 American Society for Microbiology.

Immune Recognition of Fungal Polysaccharides.

PubMed

Snarr, Brendan D; Qureshi, Salman T; Sheppard, Donald C

2017-08-28

The incidence of fungal infections has dramatically increased in recent years, in large part due to increased use of immunosuppressive medications, as well as aggressive medical and surgical interventions that compromise natural skin and mucosal barriers. There are relatively few currently licensed antifungal drugs, and rising resistance to these agents has led to interest in the development of novel preventative and therapeutic strategies targeting these devastating infections. One approach to combat fungal infections is to augment the host immune response towards these organisms. The polysaccharide-rich cell wall is the initial point of contact between fungi and the host immune system, and therefore, represents an important target for immunotherapeutic approaches. This review highlights the advances made in our understanding of the mechanisms by which the immune system recognizes and interacts with exopolysaccharides produced by four of the most common fungal pathogens: Aspergillus fumigatus , Candida albicans , Cryptococcus neoformans , and Histoplasma capsulatum . Work to date suggests that inner cell wall polysaccharides that play an important structural role are the most conserved across diverse members of the fungal kingdom, and elicit the strongest innate immune responses. The immune system senses these carbohydrates through receptors, such as lectins and complement proteins. In contrast, a greater diversity of polysaccharides is found within the outer cell walls of pathogenic fungi. These glycans play an important role in immune evasion, and can even induce anti-inflammatory host responses. Further study of the complex interactions between the host immune system and the fungal polysaccharides will be necessary to develop more effective therapeutic strategies, as well as to explore the use of immunosuppressive polysaccharides as therapeutic agents to modulate inflammation.

Fusarium solani species complex associated with carapace lesions and branchitis in captive American horseshoe crabs Limulus polyphemus.

PubMed

Tuxbury, Kathryn A; Shaw, Gillian C; Montali, Richard J; Clayton, Leigh Ann; Kwiatkowski, Nicole P; Dykstra, Michael J; Mankowski, Joseph L

2014-07-03

Captive American horseshoe crabs Limulus polyphemus housed at the National Aquarium presented with a variety of shell and gill lesions over a 3 yr period. Carapace lesions were located on both the dorsal and ventral prosoma and opisthosoma and included multifocal circular areas of tan discoloration, ulcerations, and/or pitting lesions, extending from superficial to full thickness. Gill lesions involved both the book gill cover (operculum) and individual book gill leaflets and included multifocal circular areas of tan discoloration, tan to off-white opaque proliferative lesions, and/or areas of black discoloration. Histopathology revealed fungal hyphae, with variable morphology throughout the thickened and irregular cuticle of the carapace and occasionally penetrating into subcuticular tissues, with associated amebocytic inflammation. Book gill leaflets were infiltrated by fungal hyphae and contained necrotic debris and amebocytes. Thirty-eight of 39 animals (97%) evaluated via histopathological examination had intralesional fungal hyphae. Fungal cultures of carapace and gill lesions were attempted in 26 tissue samples from 15 individuals and were positive in 13 samples (50%), with 10 cultures (77%) yielding identification to genus. Fusarium sp. was identified in 8 of the 10 cultures (80%) via culture morphology. The Fusarium solani species complex was confirmed in 6 of these 8 (75%) via polymerase chain reaction amplification of 2 different ribosomal-specific sequences of isolated fungal DNA. Ante-mortem systemic and topical treatments were performed on some affected individuals, but no appreciable change in lesions was observed. Mycotic dermatitis and branchitis are serious health issues for captive American horseshoe crabs.

Paracoccidioides brasiliensis-associated dermatitis and lymphadenitis in a dog.

PubMed

Headley, Selwyn Arlington; Pretto-Giordano, Lucienne Garcia; Di Santis, Giovana Wingeter; Gomes, Lucas Alécio; Macagnan, Rafaela; da Nóbrega, Daniela Farias; Leite, Katherine Moura; de Alcântara, Brígida Kussumoto; Itano, Eiko Nakagawa; Alfieri, Amauri Alcindo; Ono, Mario Augusto

2017-04-01

Paracoccidioidomycosis (PCM) is an endemic disease of humans from Latin America that is caused by Paracoccidioides brasiliensis and P. lutzii, with most cases of PCM in domestic animals being associated with P. brasiliensis. This study presents the clinical, cytological, mycological, serological, and molecular findings associated with P. brasiliensis in a dog from Southern Brazil. Fine needle biopsies were collected from the skin and several lymph nodes of a 5-year-old female Labrador dog that had enlargement of most superficial lymph nodes. Cytology of the skin and lymph nodes revealed pyogranulomatous dermatitis and lymphadenitis associated with fine-necked, budding fungal structures consistent with the Paracoccidioides genus of organisms; mycological culture derived from the lymph node aspirate demonstrated similar budding structures. Serological assays using exoantigens obtained from the fungal culture demonstrated that the fungal organisms derived from the lymph node were antigenically similar to P. brasiliensis by immunodiffusion and Western blot. A PCR assay, using the fungal culture as input, amplified a partial segment of the internal transcribed spacer 1 and 2 regions of P. brasiliensis; direct sequencing and phylogenetic analyses confirmed the PCR product as P. brasiliensis. The combined cytological, mycological, serological, and molecular findings confirmed a diagnosis of fungal dermatitis and lymphadenitis due to P. brasiliensis in this dog. This case represents the third description of clinical PCM in dogs and the first confirmation of mycotic dermatitis associated with P. brasiliensis in this species. The participation of dogs in the possible dissemination of PCM is reviewed, and it is proposed that dogs are probable accidental hosts in the epidemiological cycle associated with P. brasiliensis.

Skin lesion KOH exam

MedlinePlus

... present. The fungus may be related to ringworm , athlete's foot , jock itch , or another fungal infection. If the ... and the A.D.A.M. Editorial team. Athlete's Foot Read more Skin Infections Read more Tinea Infections ...

Are Bacterial Volatile Compounds Poisonous Odors to a Fungal Pathogen Botrytis cinerea, Alarm Signals to Arabidopsis Seedlings for Eliciting Induced Resistance, or Both?

PubMed Central

Sharifi, Rouhallah; Ryu, Choong-Min

2016-01-01

Biological control (biocontrol) agents act on plants via numerous mechanisms, and can be used to protect plants from pathogens. Biocontrol agents can act directly as pathogen antagonists or competitors or indirectly to promote plant induced systemic resistance (ISR). Whether a biocontrol agent acts directly or indirectly depends on the specific strain and the pathosystem type. We reported previously that bacterial volatile organic compounds (VOCs) are determinants for eliciting plant ISR. Emerging data suggest that bacterial VOCs also can directly inhibit fungal and plant growth. The aim of the current study was to differentiate direct and indirect mechanisms of bacterial VOC effects against Botrytis cinerea infection of Arabidopsis. Volatile emissions from Bacillus subtilis GB03 successfully protected Arabidopsis seedlings against B. cinerea. First, we investigated the direct effects of bacterial VOCs on symptom development and different phenological stages of B. cinerea including spore germination, mycelial attachment to the leaf surface, mycelial growth, and sporulation in vitro and in planta. Volatile emissions inhibited hyphal growth in a dose-dependent manner in vitro, and interfered with fungal attachment on the hydrophobic leaf surface. Second, the optimized bacterial concentration that did not directly inhibit fungal growth successfully protected Arabidopsis from fungal infection, which indicates that bacterial VOC-elicited plant ISR has a more important role in biocontrol than direct inhibition of fungal growth on Arabidopsis. We performed qRT-PCR to investigate the priming of the defense-related genes PR1, PDF1.2, and ChiB at 0, 12, 24, and 36 h post-infection and 14 days after the start of plant exposure to bacterial VOCs. The results indicate that bacterial VOCs potentiate expression of PR1 and PDF1.2 but not ChiB, which stimulates SA- and JA-dependent signaling pathways in plant ISR and protects plants against pathogen colonization. This study provides new evidence for bacterial VOC-elicited plant ISR that protects Arabidopsis plants from infection by the necrotrophic fungus B. cinerea. Our work reveals that bacterial VOCs primarily act via an indirect mechanism to elicit plant ISR, and have a major role in biocontrol against fungal pathogens. PMID:26941721

Antiherbivore defense mutualism under elevated carbon dioxide level: A fungal endophyte and grass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, S.; Lincoln, D.E.

1996-06-01

Previous studies have shown that insects commonly consume more when fed leaf tissue grown under CO{sub 2} enrichment, but with few negative effects on growth. However, lepidoteran larvae fed tissue infected with Balansiae fungal endophytes (which product toxic alkaloids) typically eat less but also suffer negative effects on growth and survival. This study was carried out to understand how these 2 factors may interact to affect larval consumption and growth in fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae). Infected and uninfected ramets of a single genotype of tall fescue, Festuca arundinacea Schreb., were grown under CO{sub 2} concentrations, but was notmore » influenced by infection. As expected, larvae had significantly reduced efficiency of conversion of ingested food. These 2 factors also interacted so that the lowest efficiency of conversion of ingested food was seen when both infection and an enriched atmospheric CO{sub 2} environment were present. As global atmospheric CO{sub 2} levels continue to increase, it appears that fungal endophytes will continue to be important in turfgrasses as protection against insect herbivores and may lead to increased fitness for infected plant genotypes. 47 refs., 4 figs., 1 tab.« less

Interactions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review

PubMed Central

Croft, Carys A.; Culibrk, Luka; Moore, Margo M.; Tebbutt, Scott J.

2016-01-01

Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection. The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC). The interaction between epithelial cells and conidia is multifaceted and complex, and has implications for later steps in pathogenesis. Increasing evidence has demonstrated a key role for the airway epithelium in the response to respiratory pathogens, particularly at early stages of infection; therefore, elucidating the early stages of interaction of conidia with AECs is essential to understand the establishment of infection in cohorts of at-risk patients. Here, we present a comprehensive review of the early interactions between A. fumigatus and AECs, including bronchial and alveolar epithelial cells. We describe mechanisms of adhesion, internalization of conidia by AECs, the immune response of AECs, as well as the role of fungal virulence factors, and patterns of fungal gene expression characteristic of early infection. A clear understanding of the mechanisms involved in the early establishment of infection by A. fumigatus could point to novel targets for therapy and prophylaxis. PMID:27092126

Assemblage of filamentous fungi associated with aculeate hymenopteran brood in reed galls.

PubMed

Heneberg, Petr; Bizos, Jiří; Čmoková, Adéla; Kolařík, Miroslav; Astapenková, Alena; Bogusch, Petr

2016-01-01

Monotypic stands of common reed and the reed-gall-associated insect assemblages are distributed worldwide. However, fungi associated with these assemblages have not been characterized in detail. Here we examined 5200 individuals (12 species) of immature aculeate hymenopterans or their parasitoids collected at 34 sampling sites in Central Europe. We noticed fungal outgrowth on exoskeletons of 83 (1.60%) larvae and pupae. The most common host was eudominant Pemphredon fabricii. However, the less abundant aculeate hymenopteran reed gall inquilines were infected at higher prevalence, these included Trypoxylon deceptorium, Trypoxylon minus, Hoplitis leucomelana and Hylaeus moricei (all considered new host records). We identified three fungal species, Penicillium buchwaldii (72% of cases), Aspergillus pseudoglaucus (22%) and Penicillium quebecense (6%). When multibrooded nests were affected, only a part of individuals was infected in 62% of cases. The sampling site-specific infection rate reached up to 13%, thus fungal infections should be considered an important variable driving the abundance of gall inquilines. Infections of generalist host species were more frequent than those of reed gall specialists, suggesting that suboptimal conditions decreased the immunocompetence of non-specialized species, which only occasionally nest in reed galls and feed in reed beds. Copyright © 2015 Elsevier Inc. All rights reserved.

Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells.

PubMed

Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf

2015-12-14

Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.

Detection of bacterial infection by a technetium-99m-labeled peptidoglycan aptamer.

PubMed

Ferreira, Iêda Mendes; de Sousa Lacerda, Camila Maria; Dos Santos, Sara Roberta; de Barros, André Luís Branco; Fernandes, Simone Odília; Cardoso, Valbert Nascimento; de Andrade, Antero Silva Ribeiro

2017-09-01

Nuclear medicine clinicians are still waiting for the optimal scintigraphic imaging agents capable of distinguishing between infection and inflammation, and between fungal and bacterial infections. Aptamers have several properties that make them suitable for molecular imaging. In the present study, a peptidoglycan aptamer (Antibac1) was labeled with 99m Tc and evaluated by biodistribution studies and scintigraphic imaging in infection-bearing mice. Labeling with 99m Tc was performed by the direct method and the complex stability was evaluated in saline, plasma and in the molar excess of cysteine. The biodistribution and scintigraphic imaging studies with the 99m Tc-Antibac1 were carried out in two different experimental infection models: Bacterial-infected mice (S. aureus) and fungal-infected mice (C. albicans). A 99m Tc radiolabeled library, consisting of oligonucleotides with random sequences, was used as a control for both models. Radiolabeling yields were superior to 90% and 99m Tc-Antibac1 was highly stable in presence of saline, plasma, and cysteine up to 6h. Scintigraphic images of S. aureus infected mice at 1.5 and 3.0h after 99m Tc-Antibac1 injection showed target to non-target ratios of 4.7±0.9 and 4.6±0.1, respectively. These values were statistically higher than those achieved for the 99m Tc-library at the same time frames (1.6±0.4 and 1.7±0.4, respectively). Noteworthy, 99m Tc-Antibac1 and 99m Tc-library showed similar low target to non-target ratios in the fungal-infected model: 2.0±0.3 and 2.0±0.6for 99m Tc-Antibac1 and 2.1±0.3 and 1.9 ± 0.6 for 99m Tc-library, at the same times. These findings suggest that the 99m Tc-Antibac1 is a feasible imaging probe to identify a bacterial infection focus. In addition, this radiolabeled aptamer seems to be suitable in distinguishing between bacterial and fungal infection. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Fungal keratitis secondary to Scedosporium apiospermum infection and successful treatment with surgical and medical intervention.

PubMed

Kepez Yildiz, Burcin; Hasanreisoglu, Murat; Aktas, Zeynep; Aksu, Gulsah; Kocak, Burcak Comert; Akata, Fikret

2014-04-01

To report a rare case of severe fungal keratitis caused by Scedosporium apiospermum, which was treated with a penetrating tectonic keratoplasty and aggressive medical treatment. A 62-year-old woman with a history of soil contamination of the right eye while planting vegetables presented with a severe corneal abscess and ocular pain. The patient received medical treatment and underwent tectonic keratoplasty. Both corneal scrapings and the corneal button were evaluated microscopically. The samples were sent for aerobic and anaerobic bacterial and fungal cultures. Microbiological examinations showed S. apiospermum. The isolate was sensitive to amphoterycine B, caspofungin, voriconazole, and resistant to fluconazole. No clinical improvement was achieved with topical voriconazole, vancomycin, ceftazidime, and systemic voriconazole. A penetrating tectonic keratoplasty and lensectomy with continuation of anti-fungal therapy achieved satisfactory results. A fungal etiology should be suspected in a progressive and untreatable corneal abscess. Microbiological investigation is very important in early diagnosis. Despite early diagnosis and aggressive treatment, in selected cases removing the infected tissue surgically is vital in preserving the ocular globe and vision.

Fungal prostatitis: an update.

PubMed

Mayayo, Emilio; Fernández-Silva, Fabiola

2014-06-01

Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections.

Cytokines and the regulation of fungus-specific CD4 T cell differentiation

PubMed Central

Espinosa, Vanessa; Rivera, Amariliz

2011-01-01

CD4 T cells play important and non-redundant roles in protection against infection with diverse fungi. Distinct CD4 T cell subsets can mediate protection against fungal disease where Th1 and Th17 CD4 T cell subsets have been found to promote fungal clearance and protective immunity against diverse fungal pathogens. The differentiation of naïve CD4 T cells into Th1 or Th17 cells is crucially controlled by their interaction with dendritic cells and instructed by cytokines. IL-12 and IFN-γ promote Th1 differentiation while TGF-β, IL-6, IL-1, IL-21 and IL-23 promote Th17 differentiation and maintenance. The production of these cytokines by DCs is in turn regulated by innate receptors triggered in response to fungal infection. In this review we will discuss the contributions of cytokines found to influence fungus-specific CD4 T cell differentiation and their role in defense against fungal disease. We will also highlight the contributions of innate receptors involved in recognition of fungi and how they shape cytokine secretion and CD4 T cell differentiation. PMID:22133343

Host and pathogen ecology drive the seasonal dynamics of a fungal disease, white-nose syndrome.

PubMed

Langwig, Kate E; Frick, Winifred F; Reynolds, Rick; Parise, Katy L; Drees, Kevin P; Hoyt, Joseph R; Cheng, Tina L; Kunz, Thomas H; Foster, Jeffrey T; Kilpatrick, A Marm

2015-01-22

Seasonal patterns in pathogen transmission can influence the impact of disease on populations and the speed of spatial spread. Increases in host contact rates or births drive seasonal epidemics in some systems, but other factors may occasionally override these influences. White-nose syndrome, caused by the emerging fungal pathogen Pseudogymnoascus destructans, is spreading across North America and threatens several bat species with extinction. We examined patterns and drivers of seasonal transmission of P. destructans by measuring infection prevalence and pathogen loads in six bat species at 30 sites across the eastern United States. Bats became transiently infected in autumn, and transmission spiked in early winter when bats began hibernating. Nearly all bats in six species became infected by late winter when infection intensity peaked. In summer, despite high contact rates and a birth pulse, most bats cleared infections and prevalence dropped to zero. These data suggest the dominant driver of seasonal transmission dynamics was a change in host physiology, specifically hibernation. Our study is the first, to the best of our knowledge, to describe the seasonality of transmission in this emerging wildlife disease. The timing of infection and fungal growth resulted in maximal population impacts, but only moderate rates of spatial spread. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Host and pathogen ecology drive the seasonal dynamics of a fungal disease, white-nose syndrome

PubMed Central

Langwig, Kate E.; Frick, Winifred F.; Reynolds, Rick; Parise, Katy L.; Drees, Kevin P.; Hoyt, Joseph R.; Cheng, Tina L.; Kunz, Thomas H.; Foster, Jeffrey T.; Kilpatrick, A. Marm

2015-01-01

Seasonal patterns in pathogen transmission can influence the impact of disease on populations and the speed of spatial spread. Increases in host contact rates or births drive seasonal epidemics in some systems, but other factors may occasionally override these influences. White-nose syndrome, caused by the emerging fungal pathogen Pseudogymnoascus destructans, is spreading across North America and threatens several bat species with extinction. We examined patterns and drivers of seasonal transmission of P. destructans by measuring infection prevalence and pathogen loads in six bat species at 30 sites across the eastern United States. Bats became transiently infected in autumn, and transmission spiked in early winter when bats began hibernating. Nearly all bats in six species became infected by late winter when infection intensity peaked. In summer, despite high contact rates and a birth pulse, most bats cleared infections and prevalence dropped to zero. These data suggest the dominant driver of seasonal transmission dynamics was a change in host physiology, specifically hibernation. Our study is the first, to the best of our knowledge, to describe the seasonality of transmission in this emerging wildlife disease. The timing of infection and fungal growth resulted in maximal population impacts, but only moderate rates of spatial spread. PMID:25473016

The European Paediatric Mycology Network (EPMyN): Towards a Better Understanding and Management of Fungal Infections in Children.

PubMed

Warris, Adilia

The European Paediatric Mycology Network (EPMyN) was launched in 2014 to create a European platform for research and education in the field of paediatric mycology. The EPMyN aims to address the lack of paediatric specific evidence and knowledge needed to (1) improve the management and outcome of invasive fungal infections in children and neonates and to (2) enhance and develop paediatric antifungal stewardship programmes.

The early response during the interaction of fungal phytopathogen and host plant.

PubMed

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

2017-05-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

The early response during the interaction of fungal phytopathogen and host plant

PubMed Central

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

2017-01-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

Saccharomyces cerevisiae expressing Gp43 protects mice against Paracoccidioides brasiliensis infection.

PubMed

Assis-Marques, Mariana Aprigio; Oliveira, Aline Ferreira; Ruas, Luciana Pereira; dos Reis, Thaila Fernanda; Roque-Barreira, Maria Cristina; Coelho, Paulo Sergio Rodrigues

2015-01-01

The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM). It is believed that approximately 10 million people are infected with the fungus and approximately 2% will eventually develop the disease. Unlike viral and bacterial diseases, fungal diseases are the ones against which there is no commercially available vaccine. Saccharomyces cerevisiae may be a suitable vehicle for immunization against fungal infections, as they require the stimulation of different arms of the immune response. Here we evaluated the efficacy of immunizing mice against PCM by using S. cerevisiae yeast expressing gp43. When challenged by inoculation of P. brasiliensis yeasts, immunized animals showed a protective profile in three different assays. Their lung parenchyma was significantly preserved, exhibiting fewer granulomas with fewer fungal cells than found in non-immunized mice. Fungal burden was reduced in the lung and spleen of immunized mice, and both organs contained higher levels of IL-12 and IFN-γ compared to those of non-vaccinated mice, a finding that suggests the occurrence of Th1 immunity. Taken together, our results indicate that the recombinant yeast vaccine represents a new strategy to confer protection against PCM.

Fungal prosthetic valve endocarditis with mycotic aneurysm: Case report.

PubMed

Brandão, Mariana; Almeida, Jorge; Ferraz, Rita; Santos, Lurdes; Pinho, Paulo; Casanova, Jorge

2016-09-01

Fungal prosthetic valve endocarditis is an extremely severe form of infective endocarditis, with poor prognosis and high mortality despite treatment. Candida albicans is the most common etiological agent for this rare but increasingly frequent condition. We present a case of fungal prosthetic valve endocarditis due to C. albicans following aortic and pulmonary valve replacement in a 38-year-old woman with a history of surgically corrected tetralogy of Fallot, prior infective endocarditis and acute renal failure with need for catheter-based hemodialysis. Antifungal therapy with liposomal amphotericin B was initiated prior to cardiac surgery, in which the bioprostheses were replaced by homografts, providing greater resistance to recurrent infection. During hospitalization, a mycotic aneurysm was diagnosed following an episode of acute arterial ischemia, requiring two vascular surgical interventions. Despite the complications, the patient's outcome was good and she was discharged on suppressive antifungal therapy with oral fluconazole for at least a year. The reported case illustrates multiple risk factors for fungal endocarditis, as well as complications and predictors of poor prognosis, demonstrating its complexity. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Eosinophils Subvert Host Resistance to an Intracellular Pathogen by Instigating Non-Protective IL-4 in CCR2−/− Mice

PubMed Central

Verma, Akash H.; Bueter, Chelsea L.; Rothenberg, Marc E.; Deepe, George S.

2016-01-01

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases, however, their influence on intracellular pathogens is less clear. We previously reported that CCR2−/− mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated IL-4 response. We sought to identify the cellular source promulgating interleukin (IL)-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2−/− animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity. PMID:27049063

The entomopathogenic fungus Metarhizium robertsii communicates with the insect host Galleria mellonella during infection.

PubMed

Mukherjee, Krishnendu; Vilcinskas, Andreas

2018-01-01

Parasitic fungi are the only pathogens that can infect insect hosts directly through their proteinaceous exoskeleton. Penetration of the cuticle requires the release of fungal enzymes, including proteinases, which act as virulence factors. Insects can sense fungal infections and activate innate immune responses, including the synthesis of antifungal peptides and proteinase inhibitors that neutralize the incoming proteinases. This well-studied host response is epigenetically regulated by histone acetylation/deacetylation. Here we show that entomopathogenic fungi can in turn sense the presence of insect-derived antifungal peptides and proteinase inhibitors, and respond by inducing the synthesis of chymotrypsin-like proteinases and metalloproteinases that degrade the host-derived defense molecules. The rapidity of this response is dependent on the virulence of the fungal strain. We confirmed the specificity of the pathogen response to host-derived defense molecules by LC/MS and RT-PCR analysis, and correlated this process with the epigenetic regulation of histone acetylation/deacetylation. This cascade of responses reveals that the coevolution of pathogens and hosts can involve a complex series of attacks and counterattacks based on communication between the invading fungal pathogen and its insect host. The resolution of this process determines whether or not pathogenesis is successful.

Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.

PubMed

Czakai, Kristin; Leonhardt, Ines; Dix, Andreas; Bonin, Michael; Linde, Joerg; Einsele, Hermann; Kurzai, Oliver; Loeffler, Jürgen

2016-06-27

Invasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungi Aspergillus fumigatus and Candida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted with A. fumigatus, C. albicans or LPS was performed and Krüppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.

Impact of Entomophaga maimaiga (Entomophthorales: Entomophthoraceae) on outbreak gypsy moth populations (Lepidoptera: Erebidae): the role of weather.

PubMed

Reilly, James R; Hajek, Ann E; Liebhold, Andrew M; Plymale, Ruth

2014-06-01

The fungal pathogen Entomophaga maimaiga Humber, Shimazu, and Soper is prevalent in gypsy moth [Lymantria dispar (L.)] populations throughout North America. To understand how weather-related variables influence gypsy moth-E. maimaiga interactions in the field, we measured fungal infection rates at 12 sites in central Pennsylvania over 3 yr, concurrently measuring rainfall, soil moisture, humidity, and temperature. Fungal mortality was assessed using both field-collected larvae and laboratory-reared larvae caged on the forest floor. We found significant positive effects of moisture-related variables (rainfall, soil moisture, and relative humidity) on mortality due to fungal infection in both data sets, and significant negative effects of temperature on the mortality of field-collected larvae. Lack of a clear temperature relationship with the mortality of caged larvae may be attributable to differential initiation of infection by resting spores and conidia or to microclimate effects. These relationships may be helpful in understanding how gypsy moth dynamics vary across space and time, and in forecasting how the gypsy moth and fungus will interact as they move into warmer or drier areas, or new weather conditions occur due to climate change.

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

PubMed Central

Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

2014-01-01

SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319