Anti-Mycobacterium activity of microbial peptides in a silkworm infection model with Mycobacterium smegmatis.

PubMed

Yagi, Akiho; Uchida, Ryuji; Hamamoto, Hiroshi; Sekimizu, Kazuhisa; Kimura, Ken-Ichi; Tomoda, Hiroshi

2017-05-01

An in vivo-mimic silkworm infection model with Mycobacterium smegmatis was established. When silkworms were raised at 37 °C following an injection of M. smegmatis cells (1.25 × 10 7 CFU larva -1  g -1 ) into the silkworm hemolymph, they died within 48 h. Under these conditions, four microbial peptides with anti-M. smegmatis activity, lariatin A, calpinactam, lysocin E and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active against Mycobacterium tuberculosis. These results indicate that the silkworm infection model with M. smegmatis is practically useful for the screening of therapeutically effective anti-M. tuberculosis antibiotics.

Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report.

PubMed

Cohen-Bacrie, Stéphan; David, Marion; Stremler, Nathalie; Dubus, Jean-Christophe; Rolain, Jean-Marc; Drancourt, Michel

2011-09-22

Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.

Disseminated infection with Mycobacterium tilburgii in a male immunocompromised patient.

PubMed

Temmerman, Sarah; Vandekerckhove, Linos; Sermijn, Erica; Vogelaers, Dirk; Claeys, Geert; Vaneechoutte, Mario; Cools, Piet; Callens, Steven

2014-05-01

Mycobacterium tilburgii is a nonculturable nontuberculous mycobacterium identifiable only by molecular methods. We report a case of disseminated M. tilburgii infection illustrating the importance of 16S rRNA gene sequencing to determine the responsible mycobacterial pathogen and the difficulties in tailoring antimycobacterial treatment in the absence of a culturable organism.

Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent?

PubMed

Rothel, James S; Andersen, Peter

2005-12-01

Tuberculosis is responsible for more then 2 million deaths worldwide each year and vies with HIV as the world's most fatal infectious disease. In many developing countries, attempts to control the spread of infection rely solely on identification and treatment of those with active disease, ignoring subclinical infection. However, in developed countries, large efforts are also expended to identify and give prophylactic drugs to people with latent tuberculosis infection. Until recently, the 100-year-old tuberculin skin test (Mantoux) has been the only available diagnostic test for latent tuberculosis infection, despite its many well-known limitations. Advances in scientific knowledge have led to the development of tests for tuberculosis that measure the production of interferon-gamma by T-cells stimulated in vitro with Mycobacterium tuberculosis-specific antigens. These interferon-gamma tests are highly specific and unaffected by prior Bacille Calmette-Guérin vaccination or immune reactivity to most atypical mycobacteria. They are more sensitive than the tuberculin skin test in detecting people with active tuberculosis, and their results correlate more closely with M. tuberculosis exposure risk factors than the tuberculin skin test in people likely to have latent tuberculosis infection. Science has caught up with one of the oldest diagnostic tests still in use worldwide, and the adoption of new, tuberculosis-specific interferon-gamma-based tests should move us one step closer to better control of this insidious pathogen.

Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection

PubMed Central

Silva-Gomes, Sandro; Appelberg, Rui; Larsen, Rasmus; Soares, Miguel Parreira

2013-01-01

Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (Mϕ) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1−/−) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1+/+) controls. Furthermore, Hmox1−/− mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1−/− versus Hmox1+/+ SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected Mϕ, an effect mimicked by exogenous heme administration to M. avium-infected wild-type Mϕ in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in Mϕ, contributing critically to host resistance to Mycobacterium infection. PMID:23630967

Mycobacterium chimaera left ventricular assist device infections.

PubMed

Balsam, Leora B; Louie, Eddie; Hill, Fred; Levine, Jamie; Phillips, Michael S

2017-06-01

A global outbreak of invasive Mycobacterium chimaera infections after cardiac surgery has recently been linked to bioaerosols from contaminated heater-cooler units. The majority of cases have occurred after valvular surgery or aortic graft surgery and nearly half have resulted in death. To date, infections in patients with left ventricular assist devices (LVADs) have not been characterized in the literature. We report two cases of device-associated M. chimaera infection in patients with continuous-flow LVADs and describe challenges related to diagnosis and management in this population. © 2017 Wiley Periodicals, Inc.

Mycobacterium tuberculosis Infection of Domesticated Asian Elephants, Thailand

PubMed Central

Angkawanish, Taweepoke; Sirimalaisuwan, Anucha; Kaewsakhorn, Thattawan; Boonsri, Kittikorn; Rutten, Victor P.M.G.

2010-01-01

Four Asian elephants were confirmed to be infected with Mycobacterium tuberculosis by bacterial culture, other diagnostic procedures, and sequencing of 16S–23S rDNA internal transcribed spacer region, 16S rRNA, and gyrase B gene sequences. Genotyping showed that the infectious agents originated from 4 sources in Thailand. To identify infections, a combination of diagnostic assays is essential. PMID:21122228

Mycobacterium abscessus infection in transplant recipients.

PubMed

Morales, P; Gil, A; Santos, M

2010-10-01

Mycobacterium abscessus is a ubiquitous, rapidly growing mycobacterium that colonizes organic surfaces. It is a potential pathogen, especially in immunosuppressed patients, including transplant recipients in whom disease can range from localized cutaneous lesions to disseminated infections. The purpose of this study was to describe the 12-year impact from January 1997 to December 2009 of M. abscessus infection among solid organ and bone marrow transplantations performed in adults and children. Information was obtained from the database of our Microbiology Department concerning samples, culture methods, and in vitro susceptibility testing. Isolates were classified as contaminants (C), colonization (CL), or disease (D) following standard criteria. We reviewed the medical records of affected subjects. M abscessus was isolated in 76 patients (28 C, 18 CL, and 30 D), including 11 recipients, namely 8 (73%) classified as disease displaying 1 bone marrow case and solid organ cases--4 (50%) pulmonary (2 after cystic fibrosis), 2 renal, and 1 heart transplant patients. All were adults. The localization of infection showed 2 disseminated cases, both of whom shows cutaneous primary lesions, and 6 localized in 3 cases cutaneous and in 3, respiratory. Diseases caused by M abscessus have increased in the last 5 years, possibly due to the greater number of transplants and the more focused search for the lesions. Most isolates were from lung cases, especially those with infections prior to transplantation. Respiratory and cutaneous samples were predominant, with skin lesions being an important site of primary symptom previous to dissemination of infection. Although the optimal regimen remains undefined, a favorable outcome depended mainly on a rapid diagnosis and inception of treatment following susceptibility test results. Copyright © 2010 Elsevier Inc. All rights reserved.

Virulence of two strains of Mycobacterium bovis in cattle following aerosol infection

USDA-ARS?s Scientific Manuscript database

Background Over the past two decades, highly virulent strains of Mycobacterium tuberculosis have emerged and spread rapidly in humans, suggesting a selective advantage based upon virulence. A similar scenario has not been described for Mycobacterium bovis infection in cattle (i.e., Bovine Tuberculos...

Mycobacterium genavense infections in non-HIV immunocompromised hosts: a systematic review.

PubMed

Mahmood, Maryam; Ajmal, Saira; Abu Saleh, Omar M; Bryson, Alexandra; Marcelin, Jasmine R; Wilson, John W

2018-05-01

Mycobacterium genavense is a non-tuberculous mycobacterium which can rarely cause disease in non-HIV immunocompromised hosts. We describe our experience with this unusual infection and perform a systematic review of the literature to describe the features of M. genavense infection in non-HIV immunocompromised hosts. All cases of Mycobacterium genavense infection in non-HIV patients at our institution were reviewed. In addition, we conducted a systematic review of the literature to identify previously published cases of M. genavense infections in non-HIV hosts. Two cases of M. genavense were identified at our center; a 51-year-old renal transplant recipient with a prosthetic knee joint infection and a 66-year-old woman with idiopathic CD4 lymphocytopenia with gastrointestinal tract disease. The systematic review identified 44 cases of M. genavense infection in non-HIV hosts. The most common underlying conditions were solid organ transplantation (40%), sarcoidosis (14%) and hematopoietic stem cell transplantation (7%). Disease most commonly involved the gastrointestinal tract, spleen, liver or bone marrow. Diagnosis was challenging with PCR required for identification in nearly all cases. Over one-third of patients died, which may reflect the combination of infection and underlying comorbidities. Overall cure was achieved in 61% with a mean duration of antimycobacterial therapy of 15.5 months (range 10-24). M. genavense infection is a rare mycobacterial infection in non-HIV immunocompromised hosts. It should be suspected in immunocompromised patients presenting with disseminated mycobacterial infection, acid fast bacilli on smear or histopathologic examination, with poor or no growth in mycobacterial cultures.

Transcriptome analysis of stimulated PBMC from Mycobacterium bovis infected cattle

USDA-ARS?s Scientific Manuscript database

Immunological responses of cattle to Mycobacterium bovis (M. bovis) infection are of interest in terms of understanding the biology of M. bovis infection and for the development of improved diagnostic techniques. Although considerable time and resources have been invested in understanding immune re...

Absence of Mycobacterium bovis infection in dogs and cats residing on infected cattle farms: Michigan, 2002

PubMed Central

WILKINS, M. J.; BARTLETT, P. C.; BERRY, D. E.; PERRY, R. L.; FITZGERALD, S. D.; BERNARDO, T. M.; THOEN, C. O.; KANEENE, J. B.

2008-01-01

SUMMARY A cross-sectional field study was performed to evaluate infection in dogs and cats living on farms with Mycobacterium bovis-infected cattle. The purpose was to determine pet infection status and assess their risk to farm families and/or tuberculosis-free livestock. Data and specimens were collected from 18 cats and five dogs from nine participating farms. ELISA testing for M. bovis and M. avium was conducted. Fifty-one biological samples were cultured; all were negative for M. bovis, although other Mycobacterium species were recovered. No radiographic, serological or skin test evidence of mycobacterial infection was found. These negative results may be due to the low level of M. bovis infection in the cattle and the limited duration of exposure of pets to infected cattle residing on the same farm. No evidence was found to indicate that pets residing on M. bovis-infected Michigan cattle farms pose a risk to humans or M. bovis-free livestock; however, precautionary advice for farm owners was provided. PMID:18325127

Mycobacterium lepromatosis Infections in Nuevo León, Mexico.

PubMed

Vera-Cabrera, Lucio; Escalante-Fuentes, Wendy; Ocampo-Garza, Sonia S; Ocampo-Candiani, Jorge; Molina-Torres, Carmen A; Avanzi, Charlotte; Benjak, Andrej; Busso, Philippe; Singh, Pushpendra; Cole, Stewart T

2015-06-01

The frequency of infection caused by the recently described pathogen Mycobacterium lepromatosis is unknown. Here, we describe the demographics, clinical characteristics, and therapeutic outcomes of five lepromatous leprosy patients suffering from M. lepromatosis infection in Nuevo Léon, Mexico. Diagnosis was facilitated by a new highly specific PCR procedure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Two Atypical Cases of Kingella kingae Invasive Infection with Concomitant Human Rhinovirus Infection

PubMed Central

Basmaci, Romain; Ilharreborde, Brice; Doit, Catherine; Presedo, Ana; Lorrot, Mathie; Alison, Marianne; Mazda, Keyvan; Bidet, Philippe

2013-01-01

We describe two atypical cases of Kingella kingae infection in children diagnosed by PCR, one case involving a soft tissue abscess and one case a femoral Brodie abscess. Both patients had concomitant human rhinovirus infection. K. kingae strains, isolated from an oropharyngeal swab, were characterized by multilocus sequence typing and rtxA sequencing. PMID:23784119

Mycobacterium tuberculosis Infection among Asian Elephants in Captivity.

PubMed

Simpson, Gary; Zimmerman, Ralph; Shashkina, Elena; Chen, Liang; Richard, Michael; Bradford, Carol M; Dragoo, Gwen A; Saiers, Rhonda L; Peloquin, Charles A; Daley, Charles L; Planet, Paul; Narachenia, Apurva; Mathema, Barun; Kreiswirth, Barry N

2017-03-01

Although awareness of tuberculosis among captive elephants is increasing, antituberculosis therapy for these animals is not standardized. We describe Mycobacterium tuberculosis transmission between captive elephants based on whole genome analysis and report a successful combination treatment. Infection control protocols and careful monitoring of treatment of captive elephants with tuberculosis are warranted.

Mycobacterium tuberculosis Infection among Asian Elephants in Captivity

PubMed Central

Simpson, Gary; Zimmerman, Ralph; Shashkina, Elena; Chen, Liang; Richard, Michael; Bradford, Carol M.; Dragoo, Gwen A.; Saiers, Rhonda L.; Peloquin, Charles A.; Daley, Charles L.; Planet, Paul; Narachenia, Apurva; Mathema, Barun

2017-01-01

Although awareness of tuberculosis among captive elephants is increasing, antituberculosis therapy for these animals is not standardized. We describe Mycobacterium tuberculosis transmission between captive elephants based on whole genome analysis and report a successful combination treatment. Infection control protocols and careful monitoring of treatment of captive elephants with tuberculosis are warranted. PMID:28221115

Lipid Droplets and Mycobacterium leprae Infection

PubMed Central

Elamin, Ayssar A.; Stehr, Matthias; Singh, Mahavir

2012-01-01

Leprosy is a chronic infectious disease and is a major source of morbidity in developing countries. Leprosy is caused by the obligate intracellular bacterium Mycobacterium leprae, which infects as primary target Schwann cells. Lepromatous leprosy exhibits multiple lesions of the skin, eyes, nerves, and lymph nodes. The sites of infection are characterized by the presence of foamy macrophages, fully packed with lipid droplets (LDs), which are induced by M. leprae. In the last years, it has become evident that M. tuberculosis imports lipids from foamy macrophages and is dependent on fatty acids for growth in infected macrophages. M. leprae seems to have similar mechanisms for scavenging lipids from the host. But due to the inability to culture M. leprae on laboratory media, research progresses only slowly. However, in the last years, substantial progress has been made in the field of lipid metabolism in M. leprae. Herein, we will present and summarize the lipid droplets formation and the metabolism of lipids during M. leprae infection. PMID:23209912

[Advances in the research of an animal model of wound due to Mycobacterium tuberculosis infection].

PubMed

Chen, Ling; Jia, Chiyu

2015-12-01

Tuberculosis ranks as the second deadly infectious disease worldwide. The incidence of tuberculosis is high in China. Refractory wound caused by Mycobacterium tuberculosis infection ranks high in misdiagnosis, and it is accompanied by a protracted course, and its pathogenic mechanism is still not so clear. In order to study its pathogenic mechanism, it is necessary to reproduce an appropriate animal model. Up to now the study of the refractory wound caused by Mycobacterium tuberculosis infection is just beginning, and there is still no unimpeachable model for study. This review describes two models which may reproduce a wound similar to the wound caused by Mycobacterium tuberculosis infection, so that they could be used to study the pathogenesis and characteristics of a tuberculosis wound in an animal.

A case of Manila type Mycobacterium tuberculosis infection in Japan

PubMed Central

Usami, Osamu; Nakajima, Chie; Endo, Shiro; Inomata, Shinya; Kanamori, Hajime; Hirakata, Yoichi; Uchiyama, Bine; Kaku, Mitsuo; Suzuki, Yasuhiko; Hattori, Toshio

2015-01-01

Key Clinical Message A 76-year-old Japanese woman contracted a Mycobacterium tuberculosis (TB, Manila type) infection in Japan, despite never having traveled. However, her son was treated for TB in the Philippines 3 years before he stayed at her house. Spoligotyping allows us to identify the TB genotype and identify the route of infection. PMID:26273455

High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia.

PubMed

Muchemwa, Levy; Shabir, Lakhi; Andrews, Ben; Bwalya, Mwango

2017-05-01

Tuberculosis is recognised as one of the leading causes of severe sepsis among HIV-infected patients. Most patients with Mycobacterium tuberculosis bacteraemia have advanced HIV disease with CD4 counts less than 100 cells/μl and its presentation is non-specific in most instances. This was a cross-sectional study which was done by analyzing data from 201 adult HIV-infected patients who met the inclusion criteria for severe sepsis. The prevalence of Mycobacterium tuberculosis bactraemia in the study population was 34.8%. Severe sepsis caused by other etiologies was observed in 33 (16.4%) of the participants. Concomitant infection of Mycobacterium tuberculosis bactraemia with other organisms is not uncommon in patients with severe sepsis. This cohort of HIV-infected patients had severe immunosuppression with a median CD4 count of 51 (20-136) cells/μl with moderate anaemia, mean haemoglobin 8.0 (3.0) g/dl, and were generally underweight with a mean mid upper arm circumference (MUAC) of 21.0 (3.4) cm. Mycobacterium tuberculosis bacteraemia is very common in HIV-infected patients with advanced HIV disease who present with severe sepsis. Mycobacterium tuberculosis bacteraemia co-infection with aerobic organisms is not uncommon. Factors that were independently associated with Mycobacterium tuberculosis bacteraemia in our study population were MUAC and sodium level.

Leprosy Associated with Atypical Cutaneous Leishmaniasis in Nicaragua and Honduras.

PubMed

Soto, Lucrecia Acosta; Caballero, Nelson; Fuentes, Lesny Ruth; Muñoz, Pedro Torres; Gómez Echevarría, Jose Ramón; López, Montserrat Pérez; Bornay Llinares, Fernando Jorge; Stanford, John L; Stanford, Cynthia A; Donoghue, Helen D

2017-10-01

In Central America, few cases of leprosy have been reported, but the disease may be unrecognized. Diagnosis is based on clinical criteria and histology. Preliminary field work in Nicaragua and Honduras found patients, including many children, with skin lesions clinically suggestive of atypical cutaneous leishmaniasis or indeterminate leprosy. Histology could not distinguish these diseases although acid-fast organisms were visible in a few biopsies. Lesions healed after standard antimicrobial therapy for leprosy. In the present study, patients, family members, and other community members were skin-tested and provided nasal swabs and blood samples. Biopsies were taken from a subgroup of patients with clinical signs of infection. Two laboratories analyzed samples, using local in-house techniques. Mycobacterium leprae , Leishmania spp. and Leishmania infantum were detected using polymerase chain reactions. Mycobacterium leprae DNA was detected in blood samples and nasal swabs, including some cases where leprosy was not clinically suspected. Leishmania spp. were also detected in blood and nasal swabs. Most biopsies contained Leishmania DNA and coinfection of Leishmania spp. with M. leprae occurred in 33% of cases. Mycobacterium leprae DNA was also detected and sequenced from Nicaraguan and Honduran environmental samples. In conclusion, leprosy and leishmaniasis are present in both regions, and leprosy appears to be widespread. The nature of any relationship between these two pathogens and the epidemiology of these infections need to be elucidated.

Mycobacterium fortuitum Infection at Umbilical Hernioplasty Site

PubMed Central

Chogtu, Bharti; Malik, Daliparty Vasudev; Shenoy, Vishnu Prasad

2017-01-01

Non Tuberculous Mycobacteria (NTM) are a group of rapidly growing mycobacteria and are generally considered to be of low virulence. Of late, there has been an increase in incidence of infections due to these organisms. Among them, Mycobacterium fortuitum, M. chelonae and M. abscessus are the common species which have been identified. Though they are occasionally implicated in pulmonary infections, NTM are very commonly associated with cutaneous infections, especially surgical site infections. Identification of NTM infection at such sites should be suspected when there is delayed healing of the wound. Histopathological Examination (HPE) of the wound site may reveal a classical picture of granulomas, epithelioid cells and giant cells which may lead to a suspicion of tuberculosis. It is important to perform mycobacterial culture and sensitivity testing of the wound tissue as this helps to differentiate tuberculous and non tuberculous infections. Here, we present a case of a patient who underwent mesh hernioplasty for umbilical hernia and was diagnosed with M. fortuitum infection at the site of umbilical hernioplasty. PMID:29207758

Mycobacterium avium subsp. avium found in raptors exposed to infected domestic fowl.

PubMed

Kriz, Petr; Kaevska, Marija; Bartejsova, Iva; Pavlik, Ivo

2013-09-01

We report a case of a falcon breeding facility, where raptors (both diurnal and nocturnal) were raised in contact with domestic fowl (Gallus gallus f. domesticus) infected by Mycobacterium avium subsp. avium. Fecal and environmental samples from 20 raptors and four common ravens (Corvus corax) were collected. Mycobacterium a. avium DNA was detected in feces of four raptors (bald eagle [Haliaeetus leucocephalus], eagle owl [Bubo bubo], barn owl [Tyto alba], and little owl [Athene noctua]) using triplex quantitative real-time PCR. As both the flock of domestic fowl and one of the infected raptors had the same origin (zoological collection), they might have had a common source of colonization/infection. However, the detection of M. a. avium in feces of three other raptors may point at transmission of the agent between the birds in the facility. Contact of raptors with domestic fowl infected by M. a. avium may pose a risk for transmission of the infection for them; however, raptors from the falcon breeding facility seemed to be relatively resistant to the infection.

Granulomatous lobular mastitis secondary to Mycobacterium fortuitum.

PubMed

Kamyab, Armin

2016-12-16

Granulomatous lobular mastitis is a rare inflammatory disease of the breast of unknown etiology. Most present as breast masses in women of child-bearing age. A 29-year-old female presented with a swollen, firm and tender right breast, initially misdiagnosed as mastitis. Core needle biopsy revealed findings consistent with granulomatous lobular mastitis, and cultures were all negative for an infectious etiology. She was started on steroid therapy to which she initially responded well. A few weeks later she deteriorated and was found to have multiple breast abscesses. She underwent operative drainage and cultures grew Mycobacterium fortuitum . Granulomatous lobular mastitis is a rare inflammatory disease of the breast. The definitive diagnose entails a biopsy. Other causes of chronic or granulomatous mastitis should be ruled out, including atypical or rare bacteria such as Mycobacterium fortuitum . This is the first reported case of granulomatous mastitis secondary to Mycobacterium fortuitum . With pathologic confirmation of granulomatous mastitis, an infectious etiology must be ruled out. Atypical bacteria such as Mycobacterium fortuitum may not readily grow on cultures, as with our case. Medical management is appropriate, with surgical excision reserved for refractory cases or for drainage of abscesses.

Granulomatous lobular mastitis secondary to Mycobacterium fortuitum

PubMed Central

Kamyab, Armin

2016-01-01

Granulomatous lobular mastitis is a rare inflammatory disease of the breast of unknown etiology. Most present as breast masses in women of child-bearing age. A 29-year-old female presented with a swollen, firm and tender right breast, initially misdiagnosed as mastitis. Core needle biopsy revealed findings consistent with granulomatous lobular mastitis, and cultures were all negative for an infectious etiology. She was started on steroid therapy to which she initially responded well. A few weeks later she deteriorated and was found to have multiple breast abscesses. She underwent operative drainage and cultures grew Mycobacterium fortuitum. Granulomatous lobular mastitis is a rare inflammatory disease of the breast. The definitive diagnose entails a biopsy. Other causes of chronic or granulomatous mastitis should be ruled out, including atypical or rare bacteria such as Mycobacterium fortuitum. This is the first reported case of granulomatous mastitis secondary to Mycobacterium fortuitum. With pathologic confirmation of granulomatous mastitis, an infectious etiology must be ruled out. Atypical bacteria such as Mycobacterium fortuitum may not readily grow on cultures, as with our case. Medical management is appropriate, with surgical excision reserved for refractory cases or for drainage of abscesses. PMID:28035314

Cardiac implantable electronic device infection due to Mycobacterium species: a case report and review of the literature.

PubMed

Al-Ghamdi, Bandar; Widaa, Hassan El; Shahid, Maie Al; Aladmawi, Mohammed; Alotaibi, Jawaher; Sanei, Aly Al; Halim, Magid

2016-08-24

Infection of cardiac implantable electronic devices is a serious cardiovascular disease and it is associated with a high mortality. Mycobacterium species may rarely cause cardiac implantable electronic devices infection. We are reporting a case of miliary tuberculosis in an Arab patient with dilated cardiomyopathy and a cardiac resynchronization therapy-defibrillator device that was complicated with infection of his cardiac resynchronization therapy-defibrillator device. To our knowledge, this is the third case in the literature with such a presentation and all patients died during the course of treatment. This underscores the importance of early diagnosis and management. We also performed a literature review of reported cases of cardiac implantable electronic devices infection related to Mycobacterium species. Cardiac implantable electronic devices infection due to Mycobacterium species is an uncommon but a well-known entity. Early diagnosis and prompt management may result in a better outcome.

Mycobacterium bovis infection in humans and cats in same household, Texas, USA, 2012

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis infection of cats is exceedingly rare in non-endemic regions for bovine tuberculosis. This case study describes the diagnosis and clinical management of pulmonary M. bovis infection in two indoor-housed cats and their association with at least one M. bovis-infected human in Texas...

Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis.

PubMed

Esther, Charles R; Esserman, Denise A; Gilligan, Peter; Kerr, Alan; Noone, Peadar G

2010-03-01

Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear. Microbiological data was obtained from 1216 CF patients over 8years (481+/-55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203+/-23 patients/year) with longitudinal data. Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (-2.52 vs. -1.64% predicted FEV(1)/year, p<0.05). NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline. Copyright (c) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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.

Mycobacterium tuberculosis infection in grazing cattle in central Ethiopia.

PubMed

Ameni, Gobena; Vordermeier, Martin; Firdessa, Rebuma; Aseffa, Abraham; Hewinson, Glyn; Gordon, Stephen V; Berg, Stefan

2011-06-01

A preliminary study to characterise mycobacteria infecting tuberculous cattle from two different management systems in central Ethiopia was carried out. Approximately 27% of isolates from grazing cattle were Mycobacterium tuberculosis, while cattle in a more intensive-production system were exclusively infected with M. bovis. The practice of local farmers discharging chewed tobacco directly into the mouths of pastured cattle was identified as a potential route of human-to-cattle transmission of M. tuberculosis. Copyright © 2010 Elsevier Ltd. All rights reserved.

In situ cytokine expression in pulmonary granulomas of cattle experimentally infected by aerosolized Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis is the cause of tuberculosis in most animal species, including cattle and is a serious zoonotic pathogen. In humans, M. bovis infection can result in disease clinically indistinguishable from that caused by Mycobacterium tuberculosis, the cause of most tuberculosis in humans. Reg...

Mycobacterium intracellulare infection of the shoulder and spine in a patient with steroid-treated systemic Lupus erythematosus

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

Zvetina, J.R.; Rubinstein, H.; Demos, T.C.

1982-05-01

Atypical mycobacterial infections of bone are rare. A patient with systemic lupus erythematosus treated with steroids developed an M. intracellulare infection of the shoulder and spine. These infections are insidious and diagnosis is difficult. Marked involvement of one joint, large effusion, or aspirated small synovial fragments suggest an atypical tuberculous joint infection.

Mycobacterium avium subsp. paratuberculosis infection, immunology and pathology of livestock

USDA-ARS?s Scientific Manuscript database

Mycobacterium avium subsp. paratuberculosis (MAP) infection in ruminants leads to a chronic and progressive enteric disease (Johne’s disease) that results in loss of intestinal function, poor body condition, and eventual death. Transmission is primarily through a fecal-oral route in neonates but con...

Mycobacterium marinum infections in fish and humans in Israel.

PubMed

Ucko, M; Colorni, A

2005-02-01

Israeli Mycobacterium marinum isolates from humans and fish were compared by direct sequencing of the 16S rRNA and hsp65 genes, restriction mapping, and amplified fragment length polymorphism analysis. Significant molecular differences separated all clinical isolates from the piscine isolates, ruling out the local aquaculture industry as the source of human infections.

Mycobacterium marinum Infections in Fish and Humans in Israel

PubMed Central

Ucko, M.; Colorni, A.

2005-01-01

Israeli Mycobacterium marinum isolates from humans and fish were compared by direct sequencing of the 16S rRNA and hsp65 genes, restriction mapping, and amplified fragment length polymorphism analysis. Significant molecular differences separated all clinical isolates from the piscine isolates, ruling out the local aquaculture industry as the source of human infections. PMID:15695698

Total hip replacement infected with Mycobacterium tuberculosis complicated by Addison disease and psoas muscle abscess: a case report.

PubMed

De Nardo, Pasquale; Corpolongo, Angela; Conte, Aristide; Gentilotti, Elisa; Narciso, Pasquale

2012-01-10

Prosthetic joint infection due to Mycobacterium tuberculosis is occasionally encountered in clinical practice. To the best of our knowledge, this is the first report of a prosthetic joint infection due to Mycobacterium tuberculosis complicated by psoas abscesses and secondary Addison disease. A 67-year-old immunocompetent Caucasian woman underwent total left hip arthroplasty because of osteoarthritis. After 18 months, she underwent arthroplasty revision for a possible prosthetic infection. Periprosthetic tissue specimens for bacteria were negative, and empirical antibiotic therapy was unsuccessful. She was then admitted to our department because of complications arising 22 months after arthroplasty. A physical examination revealed a sinus tract overlying her left hip and skin and mucosal pigmentation. Her levels of C-reactive protein, basal cortisol, adrenocorticotropic hormone, and sodium were out of normal range. Results of the tuberculin skin test and QuantiFERON-TB Gold test were positive. Computed tomography revealed a periprosthetic abscess and the inclusion of the left psoas muscle. Results of microbiological tests were negative, but polymerase chain reaction of a specimen taken from the hip fistula was positive for Mycobacterium tuberculosis. Our patient's condition was diagnosed as prosthetic joint infection and muscle psoas abscess due to Mycobacterium tuberculosis and secondary Addison disease. She underwent standard treatment with rifampicin, ethambutol, isoniazid, and pyrazinamide associated with hydrocortisone and fludrocortisone. At 15 months from the beginning of therapy, she was in good clinical condition and free of symptoms. Prosthetic joint infection with Mycobacterium tuberculosis is uncommon. A differential diagnosis of tuberculosis should be considered when dealing with prosthetic joint infection, especially when repeated smears and histology examination from infected joints are negative. Clinical outcomes of prosthetic joint infection by

Clinical features and follow up of 302 patients with Mycobacterium kansasii pulmonary infection: a 50 year experience

PubMed Central

Maliwan, N; Zvetina, J

2005-01-01

Aims: To analyse clinical features and treatment outcomes of patients with pulmonary Mycobacterium kansasii infection treated at Hines VA Hospital between 1952 and 1995, and followed up until 2003. Findings: 302 patients were confirmed to have M kansasii pulmonary infection; diagnosis was not made until death in 2%. The average age was 50 years old; 76% were white; all were men. Productive cough, dyspnoea, and chest pain were common; 16% were asymptomatic. Right sided, apical or subapical, thin walled cavitary infiltrate was the characteristic radiological feature. Heavy smoking, chronic obstructive pulmonary disease, alcoholism, peptic ulcer disease, coronary artery disease, prior tuberculosis, psychosis, prior pneumonia, and immunocompromising conditions were prevalent. Average follow up was 10 years and 2 months. PPD was positive in 58% of 179 tested. Two thirds of the patients required only first line drugs. Fourteen per cent required surgical intervention, none after 1977. Spontaneous resolution occurred in 1%. Aspergillosis developed in 4%. Bronchogenic carcinoma coexisted with M kansasii infection in 6% and followed it in 4%. Extrapulmonary malignancy coexisted with the infection in 4% and followed it in 6%; most involved head and neck. Eleven per cent of 224 deaths were attributed to M kansasii. Outcomes were affected by comorbidity, treatment compliance, rifampicin use, and extent of infection. Conclusions: Prognosis of M kansasii pulmonary infection is good if diagnosed and treated early, together with control of underlying conditions. Clinicians should be aware of atypical radiological manifestations of the disease when coexisting with other pulmonary or immunocompromising conditions. PMID:16085747

Mycobacterium leprae genomes from naturally infected nonhuman primates

PubMed Central

Pfister, Luz-Andrea; Housman, Genevieve; Mills, Sarah; Tarara, Ross P.; Suzuki, Koichi; Cuozzo, Frank P.; Sauther, Michelle L.; Rosenberg, Michael S.; Stone, Anne C.

2018-01-01

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild. PMID:29381722

Mycobacterium leprae genomes from naturally infected nonhuman primates.

PubMed

Honap, Tanvi P; Pfister, Luz-Andrea; Housman, Genevieve; Mills, Sarah; Tarara, Ross P; Suzuki, Koichi; Cuozzo, Frank P; Sauther, Michelle L; Rosenberg, Michael S; Stone, Anne C

2018-01-01

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild.

Mycobacterium mucogenicum and other non-tuberculous mycobacteria in potable water of a trauma hospital: a potential source for human infection.

PubMed

Fernandez-Rendon, E; Cerna-Cortes, J F; Ramirez-Medina, M A; Helguera-Repetto, A C; Rivera-Gutierrez, S; Estrada-Garcia, T; Gonzalez-Y-Merchand, J A

2012-01-01

This study examined the frequency of occurrence of non-tuberculous mycobacteria (NTM) in potable water samples from a main trauma hospital in Mexico City. Sixty-nine potable water samples were collected, 23 from each source: cistern, kitchen tap and bathroom showers. Of the 69 samples, 36 harboured NTM species. Twenty-nine of the 36 isolates were Mycobacterium mucogenicum, two Mycobacterium rhodesiae, one Mycobacterium peregrinum, one Mycobacterium fortuitum and three were Mycobacterium spp. Hospital potable water harbouring NTM represents a potential source for nosocomial infections, therefore we suggest that hospital potable water microbiological guidelines should include testing for NTM species. Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection and Pseudoaneurysm.

PubMed

O'Neil, C R; Taylor, G; Smith, S; Joffe, A M; Antonation, K; Shafran, S; Kunimoto, D

2018-02-01

We present a case of Mycobacterium chimaera infection presenting with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians should consider M. chimaera infection in those presenting with aortic dissection as a late complication of cardiovascular surgery.

Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection.

PubMed

Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; Meng, Chuang; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

2016-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

Mycobacterium fortuitum Infection following Reconstructive Breast Surgery: Differentiation from Classically Described Red Breast Syndrome.

PubMed

Cicilioni, Orlando J; Foles, Van Brandon; Sieger, Barry; Musselman, Kelly

2013-10-01

Red breast syndrome (RBS) has been described as an erythema that may be associated with 2-stage prosthetic reconstructive breast surgery using biologic mesh. RBS is differentiated from infectious cellulitis through absence of fever and laboratory abnormalities and usually has a self-limiting course. There have been no clinical reports on etiology, risk factors, or management of RBS. This report describes patient data that raise the need to rule out mycobacterial infection when RBS is being considered as a diagnosis. We present 6 cases of Mycobacterium fortuitum infection occurring after prosthetic breast reconstruction performed with a human-derived acellular dermal matrix, including the timing and course of erythema, laboratory results, treatments used, and long-term outcomes. We also describe the differential diagnoses of RBS in the context of these cases, including emergence of acid-fast bacilli and diagnostic and treatment considerations. Exact two-tailed 95% confidence intervals based on the F-distribution are provided with estimates of the incidence rates of infection. The 6 cases presented here do not fit the typical description of RBS and were caused by mycobacterium infection. Statistical evaluation of the estimated incidence rate of M. fortuitum infection in a patient thought to have RBS, which occurred 100% of the time in this series, revealed a 95% confidence interval of 54.1-100%. When presented with possible RBS, surgeons must rule out cellulitis, culture for acid-fast bacilli such as mycobacterium species, and then determine the best course of treatment. Patient counseling regarding potential household sources of infection is warranted to minimize postoperative infection risk.

Chronic Mycobacterium marinum Infection Acts as a Tumor Promoter in Japanese Medaka (Oryzias latipes)

EPA Science Inventory

An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several ...

Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

PubMed

Haytac, M Cenk; Oz, I Attila

2007-01-01

Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

Outbreak of a cutaneous Mycobacterium marinum infection in Jiangsu Haian, China.

PubMed

Feng, Yumiao; Xu, Huaisheng; Wang, Hongsheng; Zhang, Caiping; Zong, Wenkai; Wu, Qinxue

2011-11-01

Mycobacterium marinum is a slow-growing mycobacterium. In November 2008, we diagnosed a patient with M. marinum infection who worked at a fish farm in Jiangsu Haian, China. We conducted an investigation and found 18 patients with the same infection. In suspected cases, complete data were collected including medical history, clinical manifestations, laboratory features, and responses to treatment. Therapeutic regimens, including clarithromycin monotherapy or combined treatment with clarithromycin, rifampicin, and ethambutol, were prescribed. A total of 18 patients with M. marinum infection were found. All patients showed only skin lesions. Biopsies were performed and 16 patients showed infective granulomas. Acid-fast bacilli stain (Ziehl-Neelson stain) for cutaneous samples were positive in 7 patients. Ten patients were positive in purified protein derivative tests (tubercles were ≥10 mm in diameter). In 16 patients, colonies grew after tissue samples were incubated on Löwenstein-Jensen medium at 32 °C. All the isolates were identified as M. marinum by polymerase chain reaction-restriction fragment length polymorphism analysis, by direct gene sequencing, and by genotyping using mycobacterial interspersed repetitive units. Fifteen of the 18 patients were cured using clarithromycin-containing antibiotic regimens. The history of contact with fish and aquaria plays an important role in diagnosis. Clarithromycin-containing regimens were successful in most patients with M. marinum infections limited to the skin. Copyright © 2011 Elsevier Inc. All rights reserved.

Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression using experimental data

USDA-ARS?s Scientific Manuscript database

Available diagnostic assays for Mycobacterium avium subsp paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of the infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN- gamma, ELI...

Source-case investigation of Mycobacterium wolinskyi cardiac surgical site infection.

PubMed

Dupont, C; Terru, D; Aguilhon, S; Frapier, J-M; Paquis, M-P; Morquin, D; Lamy, B; Godreuil, S; Parer, S; Lotthé, A; Jumas-Bilak, E; Romano-Bertrand, S

2016-07-01

The non-tuberculous mycobacteria (NTM) Mycobacterium wolinskyi caused bacteraemia and massive colonization of an aortic prosthesis in a patient 16 days after cardiac surgery, necessitating repeat surgery and targeted antimicrobial chemotherapy. The infection control team investigated the source and conditions of infection. Peri-operative management of the patient complied with recommendations. The environmental investigation showed that although M. wolinskyi was not recovered, diverse NTM species were present in water from point-of-use taps and heater-cooler units for extracorporeal circulation. This case and increasing evidence of emerging NTM infections in cardiac surgery led to the implementation of infection control procedures in cardiac surgery wards. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Dual infection by streptococcus and atypical mycobacteria following Ahmed glaucoma valve surgery.

PubMed

Rao, Aparna; Wallang, Batriti; Padhy, Tapas Ranjan; Mittal, Ruchi; Sharma, Savitri

2013-07-01

To report a case of late postoperative endophthalmitis caused by Streptococcus pneumoniae and conjunctival necrosis by Streptococcus pneumoniae and Mycobacterium fortuitum following Ahmed glaucoma valve (AGV) surgery in a young patient. Case report of a 13-year-old boy with purulent exudates and extensive conjunctival necrosis two months following amniotic membrane graft and conjunctival closure (for conjunctival retraction post AGV for secondary glaucoma). The conjunctiva showed extensive necrosis causing exposure of the tube and plate associated with frank exudates in the area adjoining the plate and anterior chamber mandating explantation of the plate along with intravitreal antibiotics. The vitreous aspirate grew Streptococcus pneumoniae while Streptococcus pneumoniae with Mycobacterium fortuitum was isolated from the explanted plate. Despite adequate control of infection following surgery, the final visual outcome was poor owing to disc pallor. Conjunctival necrosis and retraction post-AGV can cause late postoperative co-infections by fulminant and slow-growing organisms. A close follow-up is therefore essential in these cases to prevent sight-threatening complications.

CD8 T cells and Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2015-01-01

Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. There is substantial evidence for the importance of CD4 T cells in control of tuberculosis, but the evidence for a requirement for CD8 T cells in this infection has not been proven in humans. However, animal model data support a non-redundant role for CD8 T cells in control of M. tuberculosis infection, and in humans, infection with this pathogen leads to generation of specific CD8 T cell responses. These responses include classical (MHC Class I restricted) and non-classical CD8 T cells. Here, we discuss the potential roles of CD8 T cells in defense against tuberculosis, and our current understanding of the wide range of CD8 T cell types seen in M. tuberculosis infection. PMID:25917388

Disseminated Mycobacterium avium--intracellulare complex infection in a miniature schnauzer.

PubMed

Miller, M A; Greene, C E; Brix, A E

1995-01-01

A two-year-old, spayed female, miniature schnauzer was evaluated for respiratory distress associated with a compressive cervical mass. Generalized mycobacterial infection was diagnosed from aspirates of several enlarged lymph nodes. Tissue specimens further identified Mycobacterium avium--intracellulare using polymerase chain reaction followed by nucleic acid hybridization. Treatment with enrofloxacin, clofazamine, rifampin, and interferon did not result in long-term success.

Environmental contamination with Mycobacterium avium subsp. paratuberculosis in endemically infected dairy herds

USDA-ARS?s Scientific Manuscript database

Environmental contamination with Mycobacterium avium subsp. paratuberculosis (MAP) is thought to be the primary source of infection for dairy cattle. The exact link between fecal shedding of MAP by individual cows and environmental contamination levels at the herd level was explored with a cross-se...

Anatomical distribution of Mycobacterium bovis genotypes in experimentally infected white-tailed deer

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis (M. bovis) causes tuberculosis in white-tailed deer (WTD). Natural infection of WTD with M. bovis is most closely mimicked by instilling inoculum into palatine tonsilar crypts. One hundred fifty days after intratonsilar inoculation, M. bovis was cultured from 30 tissues originati...

Catheter related line sepsis resulting from Mycobacterium chelonae infection in an immunocompromised host.

PubMed

Antony, Suresh J

2015-01-01

Almost any species of non tuberculosis mycobacterium [NTM], including M. chelonae may be associated with nosocomial infections including catheter related sepsis, pneumonia etc. We present a case of catheter related sepsis due to M. chelonae which was treated with appropriate therapy including removal of the catheter. This case serves as a reminder to include the NTM group in the differential diagnosis of these nosocomial infections.

Mixed-Strain Mycobacterium tuberculosis Infections and the Implications for Tuberculosis Treatment and Control

PubMed Central

van Helden, Paul D.; Wilson, Douglas; Colijn, Caroline; McLaughlin, Megan M.; Abubakar, Ibrahim; Warren, Robin M.

2012-01-01

Summary: Numerous studies have reported that individuals can simultaneously harbor multiple distinct strains of Mycobacterium tuberculosis. To date, there has been limited discussion of the consequences for the individual or the epidemiological importance of mixed infections. Here, we review studies that documented mixed infections, highlight challenges associated with the detection of mixed infections, and discuss possible implications of mixed infections for the diagnosis and treatment of patients and for the community impact of tuberculosis control strategies. We conclude by highlighting questions that should be resolved in order to improve our understanding of the importance of mixed-strain M. tuberculosis infections. PMID:23034327

Infection of great apes and a zoo keeper with the same Mycobacterium tuberculosis spoligotype.

PubMed

Akkerman, Onno W; van der Werf, Tjip S; Rietkerk, Frank; Eger, Tony; van Soolingen, Dick; van der Loo, Kees; van der Zanden, Adri G M

2014-04-01

An animal keeper was diagnosed with pulmonary tuberculosis (TB) after bi-annual screening for latent TB infection in zoo employees. In the same period, several bonobos of the zoo were suffering from TB as well. The Mycobacterium tuberculosis strains from both the animal keeper and the bonobos appeared identical. We provide evidence that the animals infected their keeper.

Disseminated cutaneous atypical mycobacteriosis by M. chelonae after sclerotherapy of varicose veins in a immunocompetent patient: a case report*

PubMed Central

Murback, Nathalia Dias Negrão; Higa Júnior, Minoru German; Pompílio, Maurício Antônio; Cury, Eunice Stella Jardim; Hans Filho, Gunter; Takita, Luiz Carlos

2015-01-01

Atypical mycobacteria are saprophytic organisms not transmitted from person to person, which affect mainly immunosuppressed but also immunocompetent individuals. We present a case of atypical mycobacteriosis after a vascular procedure, with widespread cutaneous lesions associated with polyarthralgia. Mycobacterium chelonae was identified by the polymerase chain reaction (PCR) method. The patient showed improvement after treatment with three antibiotics. Mycobacterium chelonae causes skin lesions after invasive procedures. The clinical form depends on the immune state of the host and on the entry points. The diagnosis is based essentially on culture and the mycobacteria is identified by PCR. We highlight the importance of investigating atypical mycobacteriosis when faced with granulomatous lesions associated with a history of invasive procedures. PMID:26312697

Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart Surgery.

PubMed

Sax, Hugo; Bloemberg, Guido; Hasse, Barbara; Sommerstein, Rami; Kohler, Philipp; Achermann, Yvonne; Rössle, Matthias; Falk, Volkmar; Kuster, Stefan P; Böttger, Erik C; Weber, Rainer

2015-07-01

Invasive Mycobacterium chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.

PubMed

Rothchild, Alissa C; Stowell, Britni; Goyal, Girija; Nunes-Alves, Cláudio; Yang, Qianting; Papavinasasundaram, Kadamba; Sassetti, Christopher M; Dranoff, Glenn; Chen, Xinchun; Lee, Jinhee; Behar, Samuel M

2017-10-24

Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF -/- ) are highly susceptible to infection with Mycobacterium tuberculosis , and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T cells also produce GM-CSF during M. tuberculosis infection. Early during infection, nonconventional iNKT cells and γδ T cells are the main source of GM-CSF, a role subsequently assumed by conventional CD4 + T cells as the infection progresses. M. tuberculosis -specific T cells producing GM-CSF are also detected in the peripheral blood of infected people. Under conditions where nonhematopoietic production of GM-CSF is deficient, T cell production of GM-CSF is protective and required for control of M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated protection in settings where GM-CSF is produced by other cell types. Finally, using an in vitro macrophage infection model, we demonstrate that GM-CSF inhibition of M. tuberculosis growth requires the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Thus, we identified GM-CSF production as a novel T cell effector function. These findings suggest that a strategy augmenting T cell production of GM-CSF could enhance host resistance against M. tuberculosis IMPORTANCE Mycobacterium tuberculosis is the bacterium that causes tuberculosis, the leading cause of death by any infection worldwide. T cells are critical components of the immune

Propagation method of saving valuable strains from a Mycobacterium liflandii infection in Western clawed frogs (Silurana tropicalis).

PubMed

Chai, Norin; Bronchain, Odile; Panteix, Gilles; Godreuil, Sylvain; de Medeiros, Christophe; Saunders, Richard; Bouts, Tim; de Luze, Amaury

2012-03-01

Mycobacterium liflandii has been responsible for an emerging infection reported in the international trade of Western clawed frogs (Silurana tropicalis). This study shows that this mycolactone-producing Mycobacterium (MPM) has expanded its distribution range to France. The results of this study suggest that the use of in vitro fertilization to maintain genetic lines could be a temporary solution for valuable S. tropicalis propagation.

Mycobacterium tuberculosis infection modulates adipose tissue biology

PubMed Central

Kühl, Anja A.; Kupz, Andreas; Vogelzang, Alexis; Mollenkopf, Hans-Joachim; Löwe, Delia; Bandermann, Silke; Dorhoi, Anca; Brinkmann, Volker

2017-01-01

Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extrapulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection. Mice infected via aerosol showed infiltration of inducible nitric oxide synthase (iNOS) or arginase 1 (Arg1)-negative F4/80+ cells, despite recruitment of CD3+, CD4+ and CD8+ T cells. Gene expression analysis of adipose tissue of aerosol Mtb-infected mice provided evidence for upregulated expression of genes associated with T cells and NK cells at 28 days post-infection. Strikingly, IFN-γ-producing NK cells and Mtb-specific CD8+ T cells were identified in perigonadal fat, specifically CD8+CD44-CD69+ and CD8+CD44-CD103+ subpopulations. Gene expression analysis of these cells revealed that they expressed IFN-γ and the lectin-like receptor Klrg1 and down-regulated CD27 and CD62L, consistent with an effector phenotype of Mtb-specific CD8+ T cells. Sorted NK cells expressed higher abundance of Klrg1 upon infection, as well. Our results reveal the ability of Mtb to persist in adipose tissue in a stressed state, and that NK cells and Mtb-specific CD8+ T cells infiltrate infected adipose tissue where they produce IFN-γ and assume an effector phenotype. We conclude that adipose tissue is a potential niche for Mtb and that due to infection CD8+ T cells and NK cells are attracted to this tissue. PMID:29040326

Mycobacterium chimaera Infection After Cardiac Surgery: First Canadian Outbreak.

PubMed

Hamad, Raphael; Noly, Pierre-Emmanuel; Perrault, Louis P; Pellerin, Michel; Demers, Philippe

2017-07-01

Recently reported in Europe and United States, disseminated Mycobacterium chimaera infection is a novel clinical entity linked to point contamination of Stockert 3T heater-cooler units used for cardiopulmonary bypass. We present here the first two cases in Canada. Both patients presented with nonspecific extracardiac symptoms 1 year after undergoing minimally invasive mitral surgical repair. Before the right diagnosis was established, the patients were initially treated with prednisone for suspected sarcoidosis. One patient is currently improving, and the other needed mitral valve repair despite aggressive treatment. Because of the nonspecific mode and timing of presentation, a high index of suspicion is necessary for the diagnosis of M. chimaera infection. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Insidious Risk of Severe Mycobacterium chimaera Infection in Cardiac Surgery Patients.

PubMed

Chand, Meera; Lamagni, Theresa; Kranzer, Katharina; Hedge, Jessica; Moore, Ginny; Parks, Simon; Collins, Samuel; Del Ojo Elias, Carlos; Ahmed, Nada; Brown, Tim; Smith, E Grace; Hoffman, Peter; Kirwan, Peter; Mason, Brendan; Smith-Palmer, Alison; Veal, Philip; Lalor, Maeve K; Bennett, Allan; Walker, James; Yeap, Alicia; Isidro Carrion Martin, Antonio; Dolan, Gayle; Bhatt, Sonia; Skingsley, Andrew; Charlett, André; Pearce, David; Russell, Katherine; Kendall, Simon; Klein, Andrew A; Robins, Stephen; Schelenz, Silke; Newsholme, William; Thomas, Stephanie; Collyns, Tim; Davies, Eleri; McMenamin, Jim; Doherty, Lorraine; Peto, Tim E A; Crook, Derrick; Zambon, Maria; Phin, Nick

2017-02-01

An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands. Parallel investigations were pursued: (1) identification of cardiopulmonary bypass-associated M. chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates. Eighteen probable cases of cardiopulmonary bypass-associated M. chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81-87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases. We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection. © Crown copyright 2016.

[Usefulness of the variable numbers of tandem repeats (VNTR) analysis for complex infections of Mycobacterium avium and Mycobacterium intracellulare].

PubMed

Tsunematsu, Noriko; Goto, Mieko; Saiki, Yumiko; Baba, Michiko; Udagawa, Tadashi; Kazumi, Yuko

2008-09-01

The bacilli which were isolated from a patient suspected of the mixed infections with Mycobacterium avium and Mycobacterium intracellulare, were analyzed. The genotypes of M. avium in the sedimented fractions of treated sputum and in some colonies isolated from Ogawa medium were compared by the Variable Numbers of Tandem Repeats (VNTR). A woman, aged 57. Mycobacterial species isolated from some colonies by culture in 2004 and 2006 and from the treated sputum in 2006, were determined by DNA sequencing analysis of the 16S rRNA gene. Also, by using VNTR, the genotype of mycobacteria was analyzed. [Results] (1) The colony isolated from Ogawa medium in 2004 was monoclonal M. avium. (2) By VNTR analyses of specimens in 2006, multiple acid-fast bacteria were found in the sputum sediment and in isolated bacteria from Ogawa medium. (3) By analyses of 16S rRNA DNA sequence, M. avium and M. intracellulare were found in the colonies isolated from the sputum sediment and the Ogawa medium in 2006. (4) The same VNTR patterns were obtained in M. avium in 2004 and 2006 when single colony was analyzed. (5) From the showerhead and culvert of the bathroom in the patient's house, M. avium was not detected. By VNTR analyses, it was considered that the mixed infections of M. avium and M. intracellulare had been generated during treatment in this case. Therefore, in the case of suspected complex infection, VNTR analysis would be a useful genotyping method in M. avium complex infection.

Mycobacterium tuberculosis infection within parotid gland Warthin tumor.

PubMed

Ozcan, Cengiz; Apa, Duygu Düşmez; Aslan, Gönül; Gülhan, Stk; Görür, Kemal

2008-11-01

Tuberculosis of the parotid gland is extremely unusual. Tuberculosis comprises 2.5% to 10% of parotid gland lesions. Two clinical forms of parotid gland tuberculosis infection exist. One is a diffuse parenchymatous disease (either primary or secondary to nodal disease), resembling common infection. The second is a chronic, slow-growing, painless, and firm parotid mass mimicking a neoplasm. Most of these patients were diagnosed after parotid gland surgery and histopathologic evaluation. Warthin tumor is a well-known benign neoplasm of the salivary glands. It is the second most common tumor of the parotid gland. Mycobacterium tuberculosis within Warthin tumor is also unusual. Five cases with parotid gland tuberculosis within Warthin tumor were reported in the literature. In this report, we present a new patient with parotid gland tuberculosis within the Warthin tumor. This type parotid gland pathology is an extremely rare entity, and to the best of our knowledge, this is the second documented case using polymerase chain reaction. We also discussed the possible mechanisms of development of infection within Warthin tumor.

LAG3 Expression in Active Mycobacterium tuberculosis Infections

PubMed Central

Phillips, Bonnie L.; Mehra, Smriti; Ahsan, Muhammad H.; Selman, Moises; Khader, Shabaana A.; Kaushal, Deepak

2016-01-01

Mycobacterium tuberculosis (MTB) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. MTB modulates several aspects of the host immune response. Lymphocyte-activation gene 3 (LAG3) is a protein with a high affinity for the CD4 receptor and is expressed mainly by regulatory T cells with immunomodulatory functions. To understand the function of LAG3 during MTB infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects of natural human infection in rhesus macaques (Macaca mulatta), was used. We show that the expression of LAG3 is highly induced in the lungs and particularly in the granulomatous lesions of macaques experimentally infected with MTB. Furthermore, we show that LAG3 expression is not induced in the lungs and lung granulomas of animals exhibiting latent tuberculosis infection. However, simian immunodeficiency virus–induced reactivation of latent tuberculosis infection results in an increased expression of LAG3 in the lungs. This response is not observed in nonhuman primates infected with non-MTB bacterial pathogens, nor with simian immunodeficiency virus alone. Our data show that LAG3 was expressed primarily on CD4+ T cells, presumably by regulatory T cells but also by natural killer cells. The expression of LAG3 coincides with high bacterial burdens and changes in the host type 1 helper T-cell response. PMID:25549835

Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection.

PubMed

Shinoda, Koji; Asahara, Hideaki; Uehara, Taira; Miyoshi, Katsue; Suzuki, Satoshi O; Iwaki, Toru; Kira, Jun-ichi

2015-02-01

We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus. © The Author(s), 2015.

Evaluation of the Mycobacterium tuberculosis SO2 vaccine using a natural tuberculosis infection model in goats.

PubMed

Bezos, J; Casal, C; Álvarez, J; Roy, A; Romero, B; Rodríguez-Bertos, A; Bárcena, C; Díez, A; Juste, R; Gortázar, C; Puentes, E; Aguiló, N; Martín, C; de Juan, L; Domínguez, L

2017-05-01

The development of new vaccines against animal tuberculosis (TB) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. In this study, the protection conferred by the Mycobacterium tuberculosis SO 2 experimental vaccine was evaluated using a natural infection model in goats. Twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously vaccinated with BCG; and (3) 10 goats were subcutaneously vaccinated with SO 2 . Four months after vaccination, all groups were merged with goats infected with Mycobacterium bovis or Mycobacterium caprae, and tested over a 40 week period using a tuberculin intradermal test and an interferon-γ assay for mycobacterial reactivity. The severity of lesions was determined at post-mortem examination and the bacterial load in tissues were evaluated by culture. The two vaccinated groups had significantly lower lesion and bacterial culture scores than the control group (P<0.05); at the end of the study, the SO 2 vaccinated goats had the lowest lesion and culture scores. These results suggest that the SO 2 vaccine provides some protection against TB infection acquired from natural exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus

PubMed Central

Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Barber, Daniel L.; Jayaraman, Pushpa

2014-01-01

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus.

PubMed

Behar, Samuel M; Carpenter, Stephen M; Booty, Matthew G; Barber, Daniel L; Jayaraman, Pushpa

2014-12-01

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease--the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Promoting effective immunity to Mycobacterium tuberculosis complex pathogens is a challenge that is of interest to the fields of human and veterinary medicine alike. We report that gamma delta T cells from virulent Mycobacterium bovis-infected cattle respond specifically and directly to complex, pro...

Epidemic of Postsurgical Infections Caused by Mycobacterium massiliense▿

PubMed Central

Duarte, Rafael Silva; Lourenço, Maria Cristina Silva; Fonseca, Leila de Souza; Leão, Sylvia Cardoso; Amorim, Efigenia de Lourdes T.; Rocha, Ingrid L. L.; Coelho, Fabrice Santana; Viana-Niero, Cristina; Gomes, Karen Machado; da Silva, Marlei Gomes; de Oliveira Lorena, Nádia Suely; Pitombo, Marcos Bettini; Ferreira, Rosa M. C.; de Oliveira Garcia, Márcio Henrique; de Oliveira, Gisele Pinto; Lupi, Otilia; Vilaça, Bruno Rios; Serradas, Lúcia Rodrigues; Chebabo, Alberto; Marques, Elizabeth Andrade; Teixeira, Lúcia Martins; Dalcolmo, Margareth; Senna, Simone Gonçalves; Sampaio, Jorge Luiz Mello

2009-01-01

An epidemic of infections after video-assisted surgery (1,051 possible cases) caused by rapidly growing mycobacteria (RGM) and involving 63 hospitals in the state of Rio de Janeiro, Brazil, occurred between August 2006 and July 2007. One hundred ninety-seven cases were confirmed by positive acid-fast staining and/or culture techniques. Thirty-eight hospitals had cases confirmed by mycobacterial culture, with a total of 148 available isolates recovered from 146 patients. Most (n = 144; 97.2%) isolates presented a PRA-hsp65 restriction pattern suggestive of Mycobacterium bolletii or Mycobacterium massiliense. Seventy-four of these isolates were further identified by hsp65 or rpoB partial sequencing, confirming the species identification as M. massiliense. Epidemic isolates showed susceptibility to amikacin (MIC at which 90% of the tested isolates are inhibited [MIC90], 8 μg/ml) and clarithromycin (MIC90, 0.25 μg/ml) but resistance to ciprofloxacin (MIC90, ≥32 μg/ml), cefoxitin (MIC90, 128 μg/ml), and doxycycline (MIC90, ≥64 μg/ml). Representative epidemic M. massiliense isolates that were randomly selected, including at least one isolate from each hospital where confirmed cases were detected, belonged to a single clone, as indicated by the analysis of pulsed-field gel electrophoresis (PFGE) patterns. They also had the same PFGE pattern as that previously observed in two outbreaks that occurred in other Brazilian cities; we designated this clone BRA100. All five BRA100 M. massiliense isolates tested presented consistent tolerance to 2% glutaraldehyde. This is the largest epidemic of postsurgical infections caused by RGM reported in the literature to date in Brazil. PMID:19403765

The purinergic P2X7 receptor is not required for control of pulmonary Mycobacterium tuberculosis infection.

PubMed

Myers, Amy J; Eilertson, Brandon; Fulton, Scott A; Flynn, Joanne L; Canaday, David H

2005-05-01

The importance in vivo of P2X7 receptors in control of virulent Mycobacterium tuberculosis was examined in a low-dose aerosol infection mouse model. P2X7(-/-) mice controlled infection in lungs as well as wild-type mice, suggesting that the P2X7 receptor is not required for control of pulmonary M. tuberculosis infection.

Central nervous system infection due to Mycobacterium haemophilum in a patient with acquired immunodeficiency syndrome.

PubMed

Buppajarntham, Aubonphan; Apisarnthanarak, Anucha; Rutjanawech, Sasinuj; Khawcharoenporn, Thana

2015-03-01

Mycobacterium haemophilum is an environmental organism that rarely causes infections in humans. We report a patient with acquired immunodeficiency syndrome who had central nervous system infection due to M. haemophilum. The diagnosis required brain tissue procurement and molecular identification method while the treatment outcome was unfavourable. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Evaluation of gamma interferon (IFN-gamma)-induced protein 10 (IP-10) responses for detection of cattle infected with Mycobacterium bovis: comparisons to IFN-gamma responses

USDA-ARS?s Scientific Manuscript database

Gamma interferon (IFN-gamma)-induced protein 10 (IP-10) has recently shown promise as a diagnostic biomarker of Mycobacterium tuberculosis infection of humans. The aim of the current study was to compare IP-10 and IFN-gamma responses upon Mycobacterium bovis infection in cattle using archived sample...

Evolution of granulomas in lungs of mice infected aerogenically with Mycobacterium tuberculosis.

PubMed

Cardona, P J; Llatjós, R; Gordillo, S; Díaz, J; Ojanguren, I; Ariza, A; Ausina, V

2000-08-01

Aerogenous infection of C57Bl/6 mice with a virulent strain of Mycobacterium tuberculosis (CL 511) leads to the formation of primary granulomas in the lung where neutrophils, macrophages and subsequently, lymphocytes accumulate progressively around an initial cluster of infected macrophages. The spread of infection through the lung parenchyma gives rise to secondary granulomas featuring numerous lymphocytes that surround a small number of infected macrophages. Afterwards, foamy macrophages add an outer layer to the granulomas, which characteristically respect the pulmonary interstitium and remain confined within the alveolar spaces. This feature, in conjunction with the constant presence of M. tuberculosis in the products of broncho-alveolar lavage, suggests that the upward bronchial migration of infected macrophages may contribute significantly to pulmonary dissemination of mycobacterial infection. The latter would be in agreement with the persistence of chronic pulmonary infection in spite of a concomitant strong T helper 1 cell response.

LAG3 expression in active Mycobacterium tuberculosis infections.

PubMed

Phillips, Bonnie L; Mehra, Smriti; Ahsan, Muhammad H; Selman, Moises; Khader, Shabaana A; Kaushal, Deepak

2015-03-01

Mycobacterium tuberculosis (MTB) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. MTB modulates several aspects of the host immune response. Lymphocyte-activation gene 3 (LAG3) is a protein with a high affinity for the CD4 receptor and is expressed mainly by regulatory T cells with immunomodulatory functions. To understand the function of LAG3 during MTB infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects of natural human infection in rhesus macaques (Macaca mulatta), was used. We show that the expression of LAG3 is highly induced in the lungs and particularly in the granulomatous lesions of macaques experimentally infected with MTB. Furthermore, we show that LAG3 expression is not induced in the lungs and lung granulomas of animals exhibiting latent tuberculosis infection. However, simian immunodeficiency virus-induced reactivation of latent tuberculosis infection results in an increased expression of LAG3 in the lungs. This response is not observed in nonhuman primates infected with non-MTB bacterial pathogens, nor with simian immunodeficiency virus alone. Our data show that LAG3 was expressed primarily on CD4(+) T cells, presumably by regulatory T cells but also by natural killer cells. The expression of LAG3 coincides with high bacterial burdens and changes in the host type 1 helper T-cell response. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Mycobacterium bovis infection in domestic pigs in Great Britain.

PubMed

Bailey, Suzanne S; Crawshaw, Timothy R; Smith, Noel H; Palgrave, Christopher J

2013-11-01

Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), infects a wide range of wild and domestic mammals. Despite a control programme spanning decades, M. bovis infection levels in cattle in Great Britain (GB) have continued to rise over recent years. As the incidence of infection in cattle and wildlife may be linked to that in swine, data relating to infection of pigs identified at slaughter were examined in this study. Between 2007 and 2011, almost all M. bovis-infected pigs originated from farms in the South-West and West-Midland regions of England. The data suggest that pigs raised outdoors or on holdings with poor biosecurity may be more vulnerable to infection with M. bovis. In the majority of cases, the same strains of M. bovis were found in pigs and cattle, despite that fact that direct contact between these species was rarely observed. Genotyping and geographical mapping data indicated that some strains found in pigs may correlate better with those present in badgers, rather than cattle. In consequence, it is proposed that pigs may represent a useful sentinel for M. bovis infection in wildlife in GB. Given the potential implications of this infection for the pig industry, and for the on-going effort to control bovine TB, the importance of understanding the epidemiology and pathogenesis of M. bovis infection, as well as monitoring its prevalence, in pigs should not be underestimated. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Atypical microbial infections of digestive tract may contribute to diarrhea in mucopolysaccharidosis patients: a MPS I case study

PubMed Central

Węgrzyn, Grzegorz; Kurlenda, Julianna; Liberek, Anna; Tylki-Szymańska, Anna; Czartoryska, Barbara; Piotrowska, Ewa; Jakóbkiewicz-Banecka, Joanna; Węgrzyn, Alicja

2005-01-01

Background Mucopolysaccharidoses are heritable, metabolic diseases caused by deficiency in an activity of one of specific lysosomal enzymes involved in degradation of mucoplysaccharides (glycosaminoglycans). Among many medical problems of patients with mucopolysaccharidoses, there are frequent episodes of diarrhea of unknown etiology. Case presentation A girl, diagnosed enzymatically for mucopolysaccharidosis type I (deficiency of α-L-iduronidase) at the age of 3 years and 9 months, was investigated until the age of 5 years and 4 months. Frequent loose stools and episodes of diarrhea, often accompanied by vomiting, were encountered. Detailed microbiological analyses were performed and atypical microbial infections (most often enetropathogenic Escherichia coli, but also other species, like Pseudomonas aeruginosa or Staphylococcus aureus, as well as adenoviruses) of the digestive tract were found in most severe diarrhea episodes. Often, isolations of pathogenic bacterial strains from stools of the investigated patient suffering from diarrhea were not obvious during the first screening, and only detailed microbiological studies, including re-isolation of colonies, gave the results of isolation of particular pathogenic strains (especially in the case of enetropathogenic E. coli). Conclusion We conclude that atypical microbial infections of digestive tract may contribute significantly to diarrhea in mucopolysaccaridosis patients. Since isolated strains were not typical and their isolation was often possible only after detailed investigation (not during a standard screening), such atypical microbial infections of digestive tract of mucopolysaccharidosis patients could be usually overlooked to date. Importantly, these atypical infections could be effectively treated with antimicrobial agents. PMID:15882450

Measuring bovine gamma delta T cell function at the site of Mycobacterium bovis infection

USDA-ARS?s Scientific Manuscript database

Bovine gamma delta T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/gamma delta T cell co-culture system to eluc...

Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature.

PubMed

Chiesi, Sheila; Piacentini, Daniela; Salerno, Nicola Duccio; Luise, Dora; Peracchi, Marta; Concia, Ercole; Cazzadori, Angelo; Piovan, Enrico; Lanzafame, Massimiliano

2017-09-01

We report the first Italian case of Mycobacterium chimaera disseminated infection in a patient with a history of cardiac surgery. The patient was initially diagnosed with sarcoidosis and started on immunosuppressive therapy. Ten months later she developed a vertebral osteomyelitis: M. chimaera was isolated from bone specimen. A review of the literature shows that M. chimaera infection occurs specifically in this population of patients, due to contamination of heater-cooler units used during cardiosurgery. Devices responsible for the transmission were produced by Sorin Group Deutschland. Mycobacterium chimaera infection should be included in the differential diagnosis for patients undergoing cardiac surgery.

Mycobacterium avium subsp. hominissuis infection in swine associated with peat used for bedding.

PubMed

Johansen, Tone Bjordal; Agdestein, Angelika; Lium, Bjørn; Jørgensen, Anne; Djønne, Berit

2014-01-01

Mycobacterium avium subsp. hominissuis is an environmental bacterium causing opportunistic infections in swine, resulting in economic losses. Additionally, the zoonotic aspect of such infections is of concern. In the southeastern region of Norway in 2009 and 2010, an increase in condemnation of pig carcasses with tuberculous lesions was seen at the meat inspection. The use of peat as bedding in the herds was suspected to be a common factor, and a project examining pigs and environmental samples from the herds was initiated. Lesions detected at meat inspection in pigs originating from 15 herds were sampled. Environmental samples including peat from six of the herds and from three peat production facilities were additionally collected. Samples were analysed by culture and isolates genotyped by MLVA analysis. Mycobacterium avium subsp. hominissuis was detected in 35 out of 46 pigs, in 16 out of 20 samples of peat, and in one sample of sawdust. MLVA analysis demonstrated identical isolates from peat and pigs within the same farms. Polyclonal infection was demonstrated by analysis of multiple isolates from the same pig. To conclude, the increase in condemnation of porcine carcasses at slaughter due to mycobacteriosis seemed to be related to untreated peat used as bedding.

Mycobacterium avium subsp. hominissuis Infection in Swine Associated with Peat Used for Bedding

PubMed Central

Johansen, Tone Bjordal; Lium, Bjørn; Jørgensen, Anne; Djønne, Berit

2014-01-01

Mycobacterium avium subsp. hominissuis is an environmental bacterium causing opportunistic infections in swine, resulting in economic losses. Additionally, the zoonotic aspect of such infections is of concern. In the southeastern region of Norway in 2009 and 2010, an increase in condemnation of pig carcasses with tuberculous lesions was seen at the meat inspection. The use of peat as bedding in the herds was suspected to be a common factor, and a project examining pigs and environmental samples from the herds was initiated. Lesions detected at meat inspection in pigs originating from 15 herds were sampled. Environmental samples including peat from six of the herds and from three peat production facilities were additionally collected. Samples were analysed by culture and isolates genotyped by MLVA analysis. Mycobacterium avium subsp. hominissuis was detected in 35 out of 46 pigs, in 16 out of 20 samples of peat, and in one sample of sawdust. MLVA analysis demonstrated identical isolates from peat and pigs within the same farms. Polyclonal infection was demonstrated by analysis of multiple isolates from the same pig. To conclude, the increase in condemnation of porcine carcasses at slaughter due to mycobacteriosis seemed to be related to untreated peat used as bedding. PMID:25431762

Mycobacterium marinum infection in fish and man: epidemiology, pathophysiology and management; a review.

PubMed

Hashish, Emad; Merwad, Abdallah; Elgaml, Shimaa; Amer, Ali; Kamal, Huda; Elsadek, Ahmed; Marei, Ayman; Sitohy, Mahmoud

2018-12-01

Mycobacterium marinum is an opportunistic pathogen inducing infection in fresh and marine water fish. This pathogen causes necrotizing granuloma like tuberculosis, morbidity and mortality in fish. The cell wall-associated lipid phthiocerol dimycocerosates, phenolic glycolipids and ESAT-6 secretion system 1 (ESX-1) are the conserved virulence determinant of the organism. Human infections with Mycobacterium marinum hypothetically are classified into four clinical categories (type I-type IV) and have been associated with the exposure of damaged skin to polluted water from fish pools or contacting objects contaminated with infected fish. Fish mycobacteriosis is clinically manifested and characterized in man by purple painless nodules, liable to develop into superficial crusting ulceration with scar formation. Early laboratory diagnosis of M. marinum including histopathology, culture and PCR is essential and critical as the clinical response to antibiotics requires months to be attained. The pathogenicity and virulence determinants of M. marinum need to be thoroughly and comprehensively investigated and understood. In spite of accumulating information on this pathogen, the different relevant data should be compared, connected and globally compiled. This article is reviewing the epidemiology, virulence factors, diagnosis and disease management in fish while casting light on the potential associated public health hazards.

Concomitant Mycobacterium avium infection and Hodgkin's disease in a lymph node from an HIV-negative child.

PubMed

de Armas, Yaxsier; Capó, Virginia; González, Ida; Mederos, Lilian; Díaz, Raúl; de Waard, Jacobus H; Rodríguez, Alberto; García, Yarmila; Cabanas, Ricardo

2011-03-01

We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin's disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started.

Cutaneous atypical mycobacteriosis in a clouded leopard (Neofelis nebulosa).

PubMed

Cerveny, Shannon N S; Thompson, Michelle E; Corner, Sarah M; Swinford, Amy K; Coke, Rob L

2013-09-01

A 16-yr-old male clouded leopard (Neofelis nebulosa) was presented for lethargy and anorexia. A cutaneous abdominal mass extending from the pubis to just caudal to the xiphoid process was present. A biopsy revealed histologic lesions consistent with an atypical mycobacterial infection consisting of diffuse, severe, pyogranulomatous dermatitis and panniculitis, with clear vacuoles and 3-5 microm, intravacuolar, faintly eosinophilic, filamentous bacilli that stained positively with FiteFaraco modified acid-fast stain. The clouded leopard had biochemical findings suggestive of chronic renal failure and euthanasia was elected. Histological evaluation of tissues collected at postmortem examination revealed multicentric B-cell lymphoma involving the oral cavity, liver, spleen, and multiple lymph nodes, bilateral testicular seminomas, thyroid follicular cell adenoma, thyroid C cell adenoma, and biliary cystadenomas. Bacterial culture and molecular sequencing identified the causative agent of the cutaneous abdominal mass as belonging to the Mycobacterium fortuitum group.

Transcriptional profiling of ileocecal valve of Holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advan...

Mycobacterium indicus pranii (MIP) mediated host protective intracellular mechanisms against tuberculosis infection: Involvement of TLR-4 mediated signaling.

PubMed

Das, Shibali; Chowdhury, Bidisha Paul; Goswami, Avranil; Parveen, Shabina; Jawed, Junaid; Pal, Nishith; Majumdar, Subrata

2016-12-01

Mycobacterium tuberculosis infection inflicts the disease Tuberculosis (TB), which is fatal if left untreated. During M. tuberculosis infection, the pathogen modulates TLR-4 receptor down-stream signaling, indicating the possible involvement of TLR-4 in the regulation of the host immune response. Mycobacterium indicus pranii (MIP) possesses immuno-modulatory properties which induces the pro-inflammatory responses via induction of TLR-4-mediated signaling. Here, we observed the immunomodulatory properties of MIP against tuberculosis infection. We have studied the detailed signaling mechanisms employed by MIP in order to restore the host immune response against the in vitro tuberculosis infection. We observed that in infected macrophages MIP treatment significantly increased the TLR-4 expression as well as activation of its downstream signaling, facilitating the activation of P38 MAP kinase. MIP treatment was able to activate NF-κB via involvement of TLR-4 signaling leading to the enhanced pro-inflammatory cytokine and NO generation in the infected macrophages and generation of protective immune response. Therefore, we may suggest that, TLR4 may represent a novel therapeutic target for the activation of the innate immune response during Tuberculosis infection. Copyright © 2016. Published by Elsevier Ltd.

Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli

PubMed Central

Malone, Kerri M.; Rue-Albrecht, Kévin; Magee, David A.; Conlon, Kevin; Schubert, Olga T.; Nalpas, Nicolas C.; Browne, John A.; Smyth, Alicia; Gormley, Eamonn; Aebersold, Ruedi; MacHugh, David E.; Gordon, Stephen V.

2018-01-01

Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M. bovis AF2122/97 and M. tuberculosis H37Rv at both the global transcriptional and the translational level via RNA-sequencing and SWATH MS. Furthermore, a bovine alveolar macrophage infection time course model was used to investigate the shared and divergent host transcriptomic response to infection with M. tuberculosis H37Rv or M. bovis AF2122/97. Significant differential expression of virulence-associated pathways between the two bacilli was revealed, including the ESX-1 secretion system. A divergent transcriptional response was observed between M. tuberculosis H37Rv and M. bovis AF2122/97 infection of bovine alveolar macrophages, in particular cytosolic DNA-sensing pathways at 48 h post-infection, and highlights a distinct engagement of M. bovis with the bovine innate immune system. The work presented here therefore provides a basis for the identification of host innate immune mechanisms subverted by virulent host-adapted mycobacteria to promote their survival during the early stages of infection. PMID:29557774

Differences in intermittent and continuous fecal shedding patterns between natural and experimental Mycobacterium avium subspecies paratuberculosis infections in cattle

USDA-ARS?s Scientific Manuscript database

The objective of this paper is to study shedding patterns of cows infected with Mycobacterium avium subsp. paratuberculosis (MAP). While multiple single farm studies of MAP dynamics were reported, there is not large-scale meta-analysis of both natural and experimental infections. Large difference...

Intracerebral Mycobacterium bovis bacilli Calmette-Guerin infection-induced immune responses in the CNS 1

PubMed Central

Lee, JangEun; Ling, Changying; Kosmalski, Michelle M.; Hulseberg, Paul; Schreiber, Heidi A.; Sandor, Matyas; Fabry, Zsuzsanna

2010-01-01

To study whether cerebral mycobacterial infection induces granuloma and protective immunity similar to systemic infection, we intracerebrally infected mice with Mycobacterium bovis bacilli Calmette-Guerin. Granuloma and IFN-γ+CD4+ T cell responses are induced in the central nervous system (CNS) similar to periphery, but the presence of IFN-γIL-17 double-positive CD4+ T cells is unique to the CNS. The major CNS source of TNF-α is microglia, with modest production by CD4+ T cells and macrophage. Protective immunity is accompanied by accumulation of Foxp3+CD4+ T cells and PD-L2+ dendritic cells, suggesting that both inflammatory and anti-inflammatory responses develop in the CNS following mycobacterial infection. PMID:19535154

Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital, Northwestern Ethiopia.

PubMed

Fanosie, Alemu; Gelaw, Baye; Tessema, Belay; Tesfay, Wogahta; Admasu, Aschalew; Yitayew, Gashaw

2016-01-01

Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients. An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant. A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013). The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed.

Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital, Northwestern Ethiopia

PubMed Central

Fanosie, Alemu; Gelaw, Baye; Tessema, Belay; Tesfay, Wogahta; Admasu, Aschalew; Yitayew, Gashaw

2016-01-01

Background Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients. Method An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant. Results A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013). Conclusion The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed. PMID:26950547

Exposure to human alveolar lining fluid enhances Mycobacterium bovis BCG vaccine efficacy against Mycobacterium tuberculosis infection in a CD8+ T-cell-dependent manner.

PubMed

Moliva, J I; Hossfeld, A P; Canan, C H; Dwivedi, V; Wewers, M D; Beamer, G; Turner, J; Torrelles, J B

2018-05-01

Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M.tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M.tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8 + T cells, and CD8 + T cells with the potential to produce interferon-γ in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8 + T cells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M.tb cell wall in vivo are relevant in the context of vaccine design.

Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques

PubMed Central

Lin, Philana Ling; Dartois, Veronique; Johnston, Paul J.; Janssen, Christopher; Via, Laura; Goodwin, Michael B.; Klein, Edwin; Barry, Clifton E.; Flynn, JoAnne L.

2012-01-01

Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB. PMID:22826237

Mycobacterium chimaera Infections Associated With Contaminated Heater-Cooler Devices for Cardiac Surgery: Outbreak Management.

PubMed

Marra, Alexandre R; Diekema, Daniel J; Edmond, Michael B

2017-08-15

The global outbreak of Mycobacterium chimaera infections associated with heater-cooler devices (HCDs) presents several important, unique challenges for the infection prevention community. The primary focus of this article is to assist hospitals in establishing a rapid response for identification, notification, and evaluation of exposed patients, and management of HCDs with regard to placement and containment, environmental culturing, and disinfection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Mycobacterium chimaera infections associated with heater-cooler units in cardiac surgery.

PubMed

Schreiber, Peter W; Sax, Hugo

2017-08-01

Mycobacterium chimaera infections following cardiac surgery have been reported from an increasing number of countries. These infections are characterized by a poor prognosis with a case fatality rate around 50% despite treatment. Since the first description in 2013, our understanding has grown steadily. Several outbreak investigations, case series, and experiments with heater-cooler units (HCUs) have been published. This review summarizes the current knowledge. M. chimaera transmission occurs during cardiopulmonary bypass via bioaerosols emitted from contaminated HCU water systems. Manifestations of M. chimaera infection comprise endocarditis, vascular graft infections, surgical site infections, and dissemination. So far, all cases were exposed to a single HCU brand. Samples from the manufacturing site as well as clonality of M. chimaera strains isolated from HCUs and patients suggest a contamination already at time of delivery representing the main source for the outbreak. Nevertheless, HCU contamination in hospitals cannot be excluded. Improved awareness of physicians of M. chimaera infection is crucial to prompt adequate diagnostic workup in patients that have been exposed to HCU presenting with compatible symptoms. For risk mitigation, strict separation between the air volume in contact with HCUs and critical clinical areas such as operating rooms is essential.

Rhinosinusitis and disseminated cutaneous infection caused by Mycobacterium chelonae in an immunocompromised patient.

PubMed

Enomoto, Yasunori; Oba, Misao; Ishii, Norihisa; Nakanaga, Kazue; Yagi, Yuki; Hasegawa, Hirotsugu; Ozawa, Yuichi; Matsui, Takashi; Yokomura, Koshi; Suda, Takafumi

2015-09-01

Mycobacterium chelonae frequently involves the skin, and the disseminated form can be observed in immunocompromised patients. In contrast, rhinosinusitis caused by the bacterium is a rare manifestation, which occurs independently of immune status. We report here a rare case of M. chelonae infection presenting as both disseminated cutaneous infection and rhinosinusitis in an immunocompromised patient. He had received systemic corticosteroids for 11 months due to cryptogenic organizing pneumonia. Before admission, he sustained injuries to his left arm and hand; those injuries succumbed to an infection that would subsequently spread to his other limbs, face, and even nasal cavities. This valuable case suggests that disseminated cutaneous infection by M. chelonae could spread to other organs. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections

PubMed Central

Khare, Sangeeta; Drake, Kenneth L.; Lawhon, Sara D.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris. A.; Adams, Leslie Garry

2016-01-01

It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer’s patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum

Systems Analysis of Early Host Gene Expression Provides Clues for Transient Mycobacterium avium ssp avium vs. Persistent Mycobacterium avium ssp paratuberculosis Intestinal Infections.

PubMed

Khare, Sangeeta; Drake, Kenneth L; Lawhon, Sara D; Nunes, Jairo E S; Figueiredo, Josely F; Rossetti, Carlos A; Gull, Tamara; Everts, Robin E; Lewin, Harris A; Adams, Leslie Garry

It has long been a quest in ruminants to understand how two very similar mycobacterial species, Mycobacterium avium ssp. paratuberculosis (MAP) and Mycobacterium avium ssp. avium (MAA) lead to either a chronic persistent infection or a rapid-transient infection, respectively. Here, we hypothesized that when the host immune response is activated by MAP or MAA, the outcome of the infection depends on the early activation of signaling molecules and host temporal gene expression. To test our hypothesis, ligated jejuno-ileal loops including Peyer's patches in neonatal calves were inoculated with PBS, MAP, or MAA. A temporal analysis of the host transcriptome profile was conducted at several times post-infection (0.5, 1, 2, 4, 8 and 12 hours). When comparing the transcriptional responses of calves infected with the MAA versus MAP, discordant patterns of mucosal expression were clearly evident, and the numbers of unique transcripts altered were moderately less for MAA-infected tissue than were mucosal tissues infected with the MAP. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis. Bayesian network modeling identified mechanistic genes, gene-to-gene relationships, pathways and Gene Ontologies (GO) biological processes that are involved in specific cell activation during infection. MAP and MAA had significant different pathway perturbation at 0.5 and 12 hours post inoculation. Inverse processes were observed between MAP and MAA response for epithelial cell proliferation, negative regulation of chemotaxis, cell-cell adhesion mediated by integrin and regulation of cytokine-mediated signaling. MAP inoculated tissue had significantly lower expression of phagocytosis receptors such as mannose receptor and complement receptors. This study reveals that perturbation of genes and cellular pathways during MAP infection resulted in host evasion by mucosal membrane barrier weakening to access entry in the ileum

Response to Alert on Possible Infections with Mycobacterium chimaera From Contaminated Heater-Cooler Devices in Hospitals Participating in the Canadian Nosocomial Infection Surveillance Program (CNISP).

PubMed

Mertz, Dominik; Macri, Jennifer; Hota, Susy; Amaratunga, Kanchana; Davis, Ian; Johnston, Lynn; Lee, Bonita; Pelude, Linda; Science, Michelle; Smith, Stephanie; Wong, Alice

2018-04-01

Canadian hospitals were made aware of the risk of Mycobacterium chimaera infection associated with heater-cooler units (HCUs) through alerts issued by the US food and Drug Administration (FDA) and the US Centers for Disease Control and Prevention (CDC). In response, most hospitals conducted retrospective reviews for infections, informed exposed patients, and initiated a requirement for informed consent with HCU use. Infect Control Hosp Epidemiol 2018;39:482-484.

Mycobacterium bovis infections in slaughter pigs in Mubende district, Uganda: a public health concern.

PubMed

Muwonge, Adrian; Johansen, Tone B; Vigdis, Edvardsen; Godfroid, Jacques; Olea-Popelka, Francisco; Biffa, Demelash; Skjerve, Eystein; Djønne, Berit

2012-09-21

Bovine tuberculosis (TB) caused by Mycobacterium bovis is primarily a disease of ruminants, particularly cattle (Bos primigenius) and buffalo (Syncerus caffer), and is endemic in most developing countries. To date, studies done in Uganda have documented the prevalence of M. bovis in cattle, humans and wild life, in addition to non-tuberculous mycobacteria in pigs. Pigs are increasingly becoming an important component of the livestock sector and share the human ecosystem in rural Uganda. It is therefore of public health interest that they are not a source of human infections. As a follow up to previously published findings on mycobacteria in pigs, this study was aimed at investigating the occurrence and molecular characteristics of M. bovis detected in slaughter pigs in Mubende district, Uganda. One hundred fifty mesenteric lymph nodes with lesions suggestive of mycobacterial infections were collected from approximately one thousand slaughtered pigs in Mubende district over a period of five months. The isolation and identification of M. bovis was done using conventional mycobacteriological methods. Mycobacteria belonging to the Mycobacterium tuberculosis complex (MTC) were identified to species level using deletion analysis. Molecular typing was done using Spoligotyping and MIRU-VNTR analysis. Molecular data were analysed and interpreted using MIRU-VNTR plus, SpolDB4.0 and the Mycobacterium bovis spoligo database. Of the examined animals, one boar and two sows from Madudu Sub County were infected with M. bovis which presented as lesions of a deep yellow colour and a grit-like texture in the mesenteric lymph nodes. This represents 2% (3/150) of the lymph nodes where lesions suggestive of mycobacterial infections were detected. Molecular analysis revealed that the isolates from the infected pigs showed identical MIRU-VNTR profile and spoligotype (SB1469). This is the first study documenting the occurrence of M. bovis in slaughter pigs in Uganda, revealing that one in

Atypical mycobacteria infection in an immunocompromised patient.

PubMed

Berger, Emily; Batra, Priya; Ralston, Jonathan; Sanchez, Miguel R; Franks, Andrew G

2010-11-15

A 61-year-old woman with systemic lupus erythematosus and Sjögren syndrome presented with a two-month history of symptomatic nodules on the buttocks and thighs that progressed to involve the dorsal aspects of the hands. On examination, infiltrative papules, nodules, and plaques were present in these regions. Biopsy specimens demonstrated granulomatous inflammation and acid-fast bacilli with the use of a Fite stain, although a culture and polymerase chain reaction analysis were negative. The patient continues to improve on long-term clarithromycin therapy. Atypical mycobacterial infections are becoming more common, especially in immunocompromised patients. Antimicrobial therapy, either with a single agent or multiple agents, often is prolonged. A high index of suspicion is warranted in immunocompromised patients, which includes those with connective-tissue diseases that are active or that require immunosuppression. In these patients, the differential diagnosis includes infectious as well as inflammatory, reactive, or neoplastic processes.

Incidence and nature of human tuberculosis due to Mycobacterium africanum in South-East England: 1977-87.

PubMed

Grange, J M; Yates, M D

1989-08-01

A total of 210 new cases of tuberculosis due to Mycobacterium africanum were registered at the South-East Regional Centre for Tuberculosis Bacteriology, Dulwich, between 1977 and 1987 inclusive. This represented 1.25% of bacteriologically-confirmed cases of tuberculosis in South-East England, an incidence slightly higher than that of disease due to M. bovis. Two variants were identified: 150 strains were typed as African I (a type associated with East Africa) and 60 as African II (a type more prevalent in West Africa). Over half the patients infected with African I strains were of Indian subcontinent ethnic origin; patients of African ethnic origin predominated in the African II group while about a fifth o patients infected with either type were of European origin. The European patients with tuberculosis due to M. africanum were notably younger than those in the same region with disease due to other tubercle bacilli. The distribution of lesions due to M. africanum was similar to that due to other tubercle bacilli in the various ethnic groups, except that genito-urinary tuberculosis was uncommon. The importance of a clinical awareness that M. africanum is a highly pathogenic and transmissible tubercle bacillus rather than an opportunist or 'atypical' mycobacterium is stressed.

Mycobacterium chimaera - a new threat for cardiac surgical patients?

PubMed

Jaworski, Radosław; Naumiuk, Łukasz; Paczkowski, Konrad; Formella, Danuta; Pek, Renata; Zieliński, Jacek; Haponiuk, Ireneusz

2017-03-01

An outbreak of invasive Mycobacterium chimaera infections associated with "heater-cooler" devices in patients treated with cardiac surgery has been described worldwide. The authors summarize the current state of knowledge regarding the epidemiology, diagnostics, treatment, and prevention of Mycobacterium chimaera infections in patients after cardiothoracic surgery.

Characterization of bovine gamma delta T cells phenotype during post-natal development and following Mycobacterium bovis vaccination or virulent infection

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis caused by Mycobacterium bovis is a globally significant veterinary health problem. Gamma delta T cells are known to participate in the immune control of mycobacterial infections. Data in human and non-human primates suggest that mycobacterial infection regulates memory/effector p...

Polyfunctional cytokine production by central memory T cells from cattle in response to Mycobacterium bovis infection and BCG vaccination

USDA-ARS?s Scientific Manuscript database

Polyfunctional T cells simultaneously produce IFN-gamma, IL-2 and TNF-alpha and play relevant roles in several chronic infections, including TB. Mycobacterium bovis infection of cattle elicits ex vivo polyfunctional T cell responses. Vaccine-elicited IFN-gamma Tcm (CD4+ CD45RO+ CCR7+) responses corr...

THE ISOLATION AND IDENTIFICATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) RECOVERED FROM LOS ANGELES POTABLE WATER, A POSSIBLE SOURCE OF INFECTION IN AIDS PATIENTS

EPA Science Inventory

Los Angeles water was investigated as a possible source of Mycobacterium avium complex (MAC) infection in patients with AIDS. MAC consists of M.avium (MA), M. intracellulare (MI) and Mycobacterium X (MX)(positive for MAC by DNA probe but not MA or MI). The study included 13 reser...

The hbhA Gene of Mycobacterium tuberculosis Is Specifically Upregulated in the Lungs but Not in the Spleens of Aerogenically Infected Mice

PubMed Central

Delogu, Giovanni; Sanguinetti, Maurizio; Posteraro, Brunella; Rocca, Stefano; Zanetti, Stefania; Fadda, Giovanni

2006-01-01

We report that hbhA is differentially regulated during Mycobacterium tuberculosis infection. Upregulation was observed in epithelial cell infection but not in macrophage infection and in the lungs but not in the spleens of infected mice, and it was greater during the early steps of infection, when bacilli disseminate from the site of primary infection. PMID:16622240

Isolation and characterization of an atypical Listeria monocytogenes associated with a canine urinary tract infection

USDA-ARS?s Scientific Manuscript database

Listeria monocytogenes, a well-described cause of encephalitis and abortion in ruminants and of food-borne illness in humans, is rarely associated with disease in companion animals. A case of urinary tract infection associated with an atypical, weakly hemolytic L. monocytogenes strain is described i...

Bacteriological diagnosis and molecular strain typing of Mycobacterium bovis and Mycobacterium caprae.

PubMed

Gormley, E; Corner, L A L; Costello, E; Rodriguez-Campos, S

2014-10-01

The primary isolation of a Mycobacterium sp. of the Mycobacterium tuberculosis complex from an infected animal provides a definitive diagnosis of tuberculosis. However, as Mycobacterium bovis and Mycobacterium caprae are difficult to isolate, particularly for animals in the early stages of disease, success is dependent on the optimal performance of all aspects of the bacteriological process, from the initial choice of tissue samples at post-mortem examination or clinical samples, to the type of media and conditions used to cultivate the microorganism. Each step has its own performance characteristics, which can contribute to sensitivity and specificity of the procedure, and may need to be optimized in order to achieve the gold standard diagnosis. Having isolated the slow-growing mycobacteria, species identification and fine resolution strain typing are keys to understanding the epidemiology of the disease and to devise strategies to limit transmission of infection. New technologies have emerged that can now even discriminate different isolates from the same animal. In this review we highlight the key factors that contribute to the accuracy of bacteriological diagnosis of M. bovis and M. caprae, and describe the development of advanced genotyping techniques that are increasingly used in diagnostic laboratories for the purpose of supporting detailed epidemiological investigations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Atypical Cutaneous Manifestations in Syphilis.

PubMed

Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

2016-05-01

Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

PubMed Central

González-Pérez, Mónica; Mariño-Ramírez, Leonardo; Parra-López, Carlos Alberto; Murcia, Martha Isabel; Marquina, Brenda; Mata-Espinoza, Dulce; Rodriguez-Míguez, Yadira; Baay-Guzman, Guillermina J.; Huerta-Yepez, Sara

2013-01-01

The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue. PMID:23959717

Polyfunctional cytokine production by central memory T cells from cattle in response to Mycobacterium bovis infection and BCG vaccination

USDA-ARS?s Scientific Manuscript database

Polyfunctional T cells simultaneously produce IFN-gamma, IL-2 and TNF-alpha and play relevant roles in several chronic infections, including TB. Mycobacterium bovis infection of cattle elicits ex vivo polyfunctional T cell responses. Vaccine-elicited IFN-gamma Tcm (CD4 plus CD45RO plus CCR7 plus) re...

Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

USDA-ARS?s Scientific Manuscript database

The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

Establishment of a Neonatal Rhesus Macaque Model to Study Mycobacterium tuberculosis Infection

PubMed Central

Cepeda, Magdalena; Salas, Mary; Folwarczny, Jessica; Leandro, Ana C.; Hodara, Vida L.; de la Garza, Melissa A.; Dick, Edward J.; Owston, Michael; Armitige, Lisa Y.; Gauduin, Marie-Claire

2014-01-01

Summary Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4–6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS. PMID:24388650

Disseminated Mycobacterium tuberculosis Infection in a Dog

PubMed Central

Martinho, Anna Paula Vitirito; Franco, Marília Masello Junqueira; Ribeiro, Márcio Garcia; Perrotti, Isabella Belletti Mutt; Mangia, Simone Henriques; Megid, Jane; Vulcano, Luiz Carlos; Lara, Gustavo Henrique Batista; Santos, Adolfo Carlos Barreto; Leite, Clarice Queico Fujimura; de Carvalho Sanches, Osimar; Paes, Antonio Carlos

2013-01-01

An uncommon disseminated Mycobacterium tuberculosis infection is described in a 12-year-old female dog presenting with fever, dyspnea, cough, weight loss, lymphadenopathy, melena, epistaxis, and emesis. The dog had a history of close contact with its owner, who died of pulmonary tuberculosis. Radiographic examination revealed diffuse radio-opaque images in both lung lobes, diffuse visible masses in abdominal organs, and hilar and mesenteric lymphadenopathy. Bronchial washing samples and feces were negative for acid-fast organisms. Polymerase chain reaction (PCR)-based species identification of bronchial washing samples, feces, and urine revealed M. tuberculosis using PCR-restriction enzyme pattern analysis-PRA. Because of public health concerns, which were worsened by the physical condition of the dog, euthanasia of the animal was recommended. Rough and tough colonies suggestive of M. tuberculosis were observed after microbiological culture of lung, liver, spleen, heart, and lymph node fragments in Löwenstein-Jensen and Stonebrink media. The PRA analysis enabled diagnosis of M. tuberculosis strains isolated from organs. PMID:23339199

Effects of recombinant granulocyte-colony stimulating factor administration during Mycobacterium avium infection in mice

PubMed Central

Gonçalves, A S; Appelberg, R

2001-01-01

Granulocyte colony-stimulating factor (G-CSF) administration in vivo has been shown to improve the defence mechanisms against infection by different microbes. Here we evaluated a possible protective role of this molecule in a mouse model of mycobacterial infection. The administration of recombinant G-CSF promoted an extensive blood neutrophilia but failed to improve the course of Mycobacterium avium infection in C57Bl/6 or beige mice. G-CSF administration also failed to improve the efficacy of a triple chemotherapeutic regimen (clarithromycin + ethambutol + rifabutin). G-CSF treatment did not protect interleukin-10 gene disrupted mice infected with M. avium. Spleen cells from infected mice treated with G-CSF had a decreased priming for antigen-specific production of interferon gamma compared to control infected mice. Our data do not substantiate previous reports on the protective activity of G-CSF in antimycobacterial immunity using mouse models. PMID:11422200

The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

PubMed

Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

2016-04-05

Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

Clinical and Histopathologic Ocular Findings in Disseminated Mycobacterium chimaera Infection after Cardiothoracic Surgery.

PubMed

Zweifel, Sandrine A; Mihic-Probst, Daniela; Curcio, Christine A; Barthelmes, Daniel; Thielken, Andrea; Keller, Peter M; Hasse, Barbara; Böni, Christian

2017-02-01

To investigate and characterize clinical and histopathologic ocular findings in patients with disseminated infection with Mycobacterium chimaera, a slow-growing nontuberculous mycobacterium (NTM), subsequent to cardiothoracic surgery. Observational case series. Five white patients (10 eyes). Analysis of clinical ocular findings, including visual acuity, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), and fluorescein angiography/indocyanine green (ICG) angiography findings, of patients with a disseminated M. chimaera infection. Biomicroscopic and multimodal imaging findings were compared with the histopathology of 1 patient. Clinical and histopathologic ocular findings of M. chimaera. The mean age of the 5 male patients, diagnosed with endocarditis or aortic graft infection, was 57.8 years. Clinical ocular findings included anterior and intermediate uveitis, optic disc swelling, and white-yellowish choroidal lesions. Multifocal choroidal lesions were observed bilaterally in all patients and were hyperfluorescent on fluorescein angiography, hypofluorescent on ICG angiography, and correlated with choroidal lesions on SD OCT. The extent of choroidal lesions varied from few in 2 patients to widespread miliary lesions in 3 patients leading to localized choroidal thickening with elevation of the overlying retinal layers. Spectral-domain optical coherence tomography through regressing lesions revealed altered outer retinal layers and choroidal hypertransmission. The ocular findings were correlated with the course of the systemic disease. Patients with few choroidal lesions had a favorable outcome, whereas all patients with widespread chorioretinitis died of systemic complications of M. chimaera infection despite long-term targeted antimicrobial therapy. Ocular tissue was obtained from 1 patient at autopsy. Necropsy of 2 eyes of 1 patient revealed prominent granulomatous lymphohistiocytic choroiditis with

Mycobacterium tuberculosis infection among persons who inject drugs in San Diego, California.

PubMed

Armenta, R F; Collins, K M; Strathdee, S A; Bulterys, M A; Munoz, F; Cuevas-Mota, J; Chiles, P; Garfein, R S

2017-04-01

Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use. To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA. PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression. A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others. Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region.

Mycobacterium bovis infections in domesticated non-bovine mammalian species. Part 2: A review of diagnostic methods.

PubMed

Broughan, J M; Crawshaw, T R; Downs, S H; Brewer, J; Clifton-Hadley, R S

2013-11-01

Despite the large host range of Mycobacterium bovis, ante-mortem diagnostic tests for the infection mostly lack sensitivity/specificity and/or remain unvalidated in non-bovine species. The epidemiology and importance of M. bovis infection in these species are discussed in the first part of this two-part review. This second part focuses on the diagnostic options available to identify infected species such as sheep, goats, dogs, cats, and camelids, and highlights the significant challenges posed, both in establishing estimates of disease prevalence and in controlling infections in these species, in the absence of fully validated tests. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Analysis of cytokine mRNA expression using a novel chromogenic in situ hybridization method in pulmonary granulomas of cattle experimentally infected by aerosolized Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis is the cause of tuberculosis in most animal species, including cattle and is a serious zoonotic pathogen. In humans, M. bovis infection can result in disease clinically indistinguishable from that caused by Mycobacterium tuberculosis, the cause of most tuberculosis in humans. Reg...

Deep Whole-Genome Sequencing to Detect Mixed Infection of Mycobacterium tuberculosis

PubMed Central

Gan, Mingyu; Liu, Qingyun; Yang, Chongguang; Gao, Qian; Luo, Tao

2016-01-01

Mixed infection by multiple Mycobacterium tuberculosis (MTB) strains is associated with poor treatment outcome of tuberculosis (TB). Traditional genotyping methods have been used to detect mixed infections of MTB, however, their sensitivity and resolution are limited. Deep whole-genome sequencing (WGS) has been proved highly sensitive and discriminative for studying population heterogeneity of MTB. Here, we developed a phylogenetic-based method to detect MTB mixed infections using WGS data. We collected published WGS data of 782 global MTB strains from public database. We called homogeneous and heterogeneous single nucleotide variations (SNVs) of individual strains by mapping short reads to the ancestral MTB reference genome. We constructed a phylogenomic database based on 68,639 homogeneous SNVs of 652 MTB strains. Mixed infections were determined if multiple evolutionary paths were identified by mapping the SNVs of individual samples to the phylogenomic database. By simulation, our method could specifically detect mixed infections when the sequencing depth of minor strains was as low as 1× coverage, and when the genomic distance of two mixed strains was as small as 16 SNVs. By applying our methods to all 782 samples, we detected 47 mixed infections and 45 of them were caused by locally endemic strains. The results indicate that our method is highly sensitive and discriminative for identifying mixed infections from deep WGS data of MTB isolates. PMID:27391214

Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates

PubMed Central

Zheng, Chao; Li, Song; Luo, Zhongyue; Pi, Rui; He, Qingxia; Tang, Ke; Luo, Mei; Li, Yuqing; Couvin, David; Rastogi, Nalin

2015-01-01

Mixed infections and heteroresistance of Mycobacterium tuberculosis contribute to the difficulty of diagnosis, treatment, and control of tuberculosis. However, there is still no proper solution for these issues. This study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors. A total of 499 resistant and susceptible isolates were subjected to spoligotyping and 24-locus variable-number tandem repeat methods to analyze their genotypic lineages and the occurrence of mixed infections. Two hundred ninety-two randomly selected isolates were sequenced on their rpoB gene to examine mutations and heteroresistance. The results showed that 12 patients had mixed infections, and the corresponding isolates belonged to Manu2 (n = 8), Beijing (n = 2), T (n = 1), and unknown (n = 1) lineages. Manu2 was found to be significantly associated with mixed infections (odds ratio, 47.72; confidence interval, 9.68 to 235.23; P < 0.01). Four isolates (1.37%) were confirmed to be heteroresistant, which was caused by mixed infections in three (75%) isolates; these belonged to Manu2. Additionally, 3.8% of the rifampin-resistant isolates showing no mutation in the rpoB gene were significantly associated with mixed infections (χ2, 56.78; P < 0.01). This study revealed for the first time that Manu2 was the predominant group in the cases of mixed infections, and this might be the main reason for heteroresistance and a possible mechanism for isolates without any mutation in the rpoB gene to become rifampin resistant. Further studies should focus on this lineage to clarify its relevance to mixed infections. PMID:25903578

Healthcare-Associated Mycobacterium chimaera Infection Subsequent to Heater-Cooler Device Exposure During Cardiac Surgery.

PubMed

Ninh, Allen; Weiner, Menachem; Goldberg, Andrew

2017-10-01

A SERIES of reports in the United States and Europe have linked Mycobacterium chimaera infections to contaminated heater-cooler devices used during cardiac surgery. Heater-cooler devices commonly are used for cardiopulmonary bypass during cardiac surgery. M. chimaera is a slow-growing nontuberculous mycobacterium that has been shown to cause cardiac complications that can lead to fatal disease following cardiac surgery. Given that more than 250,000 cardiothoracic surgical procedures requiring cardiopulmonary bypass take place each year in the United States, the estimated number of patient exposures to M. chimaera has prompted a public health crisis. The goal of this review is to summarize the present status of the M. chimaera outbreak and provide cardiothoracic surgeons, cardiac anesthesiologists, and other clinicians with current approaches to patient management and to discuss risk mitigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Sporotrichoid Mycobacterium marinum infection of the face following a cat scratch.

PubMed

Phan, Tai Anh; Relic, John

2010-02-01

Mycobacterium marinum infections in humans uncommonly affect the face and are not known to be associated with cat scratches. We describe a 24-year-old woman who presented with a 3-month history of multiple tender, occasionally discharging cystic nodules involving the left side of her face in a sporotrichoid distribution. She had suffered a cat scratch to her left lower eyelid 3 weeks before the onset of the eruption and owned multiple tropical fish tanks. She was systemically well and had no lymphadenopathy. She had a background history of a 4.5-mm-thick nodular melanoma of her temple treated by wide local excision and negative sentinel lymph node biopsy 4 years prior. Skin biopsies showed multiple variably sized granulomas surrounded by thick cuffs of lymphocytes involving the superficial and deep dermis with no organisms seen on Ziehl-Neelsen, peroidic acid-Schiff and methenamine silver stains. Laboratory investigations showed a mildly raised erythrocyte sedimentation rate but normal full blood count and C-reactive protein. Fluid from the left cheek grew an acid-fast bacillus identified as Mycobacterium marinum. The skin eruption cleared after 5-month treatment with oral clarithromycin 500 mg twice daily and rifampicin 600 mg daily.

Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases.

PubMed

Scriven, James E; Scobie, Antonia; Verlander, Neville Q; Houston, Angela; Collyns, Tim; Cajic, Vjeran; Kon, Onn Min; Mitchell, Tamara; Rahama, Omar; Robinson, Amy; Withama, Shirmila; Wilson, Peter; Maxwell, David; Agranoff, Daniel; Davies, Eleri; Llewelyn, Meirion; Soo, Shiu-Shing; Sahota, Amandip; Cooper, Mike; Hunter, Michael; Tomlins, Jennifer; Tiberi, Simon; Kendall, Simon; Dedicoat, Martin; Alexander, Eliza; Fenech, Teresa; Zambon, Maria; Lamagni, Theresa; Smith, E Grace; Chand, Meera

2018-05-24

Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through on-going surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30), and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotising granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (IQR 20-39) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower CRP as factors associated with better survival. Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery. Copyright © 2018. Published by Elsevier Ltd.

[Frontier of mycobacterium research--host vs. mycobacterium].

PubMed

Okada, Masaji; Shirakawa, Taro

2005-09-01

During the past decade, we have observed advance in tuberculosis research including novel vaccines, innate immunity (TLR), SNIP analysis and molecular mechanism of drug resistance. Worldwide genome project enabled the whole genome sequence of host resistant against tuberculosis as well as the whole genome sequence of M. tuberculosis H37Rv. DNA technology has also provided a great impact on the development of novel vaccine against TB. In this symposium, we have invited leading researchers in the field of the frontier study of Mycobacterium research in order to provide general overview of the cutting edge of frontier research. Molecular mechanism of drug resistance of M. tuberculosis has been clarified. On the other hand, molecular mechanism of host-defence (insusceptibility of host) against M. tuberculosis has not yet elucidated. Dr. Taro Shirakawa (Kyoto University) reviewed the susceptibility genes of host in TB infection and presented candidate genes associated with multi-drug resistant tuberculosis. Dr. Naoto Keicho (International Medical Center of Japan) tried to identify host genetic factors involved in susceptibility to pulmonary Mycobacterium avium complex (MAC) infection by candidate gene approach and genome-wide approach. In Japan, Dr. Masaji Okada (National Hospital Organization Kinki-Chuo Chest Medical Center) has been engaged actively in the development of new tuberculosis vaccines (HVJ-liposome/Hsp65 DNA + IL-12 DNA vaccine and recombinant 72f BCG vaccine). He showed basic strategy for construction of new candidate vaccines and also showed significant efficacy on the protection of tuberculosis infection using cynomolgus monkeys, which are very similar to human tuberculosis. Dr. Hatsumi Taniguchi (University of Occupational and Environmental Health) presented that M. tuberculosis mIHF and the neighbor genes went into a dormacy-like state of M. smegmatis in J774 macrophage cells. This study might provide a weapon for elucidating the mechanism of dormacy

Surgical management of cutaneous infection caused by atypical mycobacteria after penetrating injury: the hidden dangers of horticulture.

PubMed

Holland, J; Smith, C; Childs, P A; Holland, A J

1997-02-01

We identified two patients in a 12-month period who presented with cutaneous infection and secondary lymph node involvement from atypical mycobacterial infection after minor gardening injuries. One patient had a coinfection with Nocardia asteroides. Both patients required multiple surgical interventions, despite appropriate antibiotic therapy, before resolution of the disease. The course of the infection was characterized by chronic relapses with complete healing at 12 to 18 months after the original injury. The identification and management of this clinical problem are reviewed.

Computational and empirical studies predict Mycobacterium tuberculosis-specific T cells as a biomarker for infection outcome

DOE PAGES

Marino, Simeone; Gideon, Hannah P.; Gong, Chang; ...

2016-04-11

Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2-year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identifiedmore » T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. As a result, we emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery.« less

Computational and empirical studies predict Mycobacterium tuberculosis-specific T cells as a biomarker for infection outcome

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

Marino, Simeone; Gideon, Hannah P.; Gong, Chang

Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2-year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identifiedmore » T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. As a result, we emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery.« less

Typical and atypical symptoms of gastro esophageal reflux disease: Does Helicobacter pylori infection matter?

PubMed

Grossi, Laurino; Ciccaglione, Antonio Francesco; Marzio, Leonardo

2015-11-06

To analyze whether the presence of Helicobacter pylori (H. pylori) infection could affect the quality of symptoms in gastro-esophageal reflux disease (GERD) patients. one hundred and forty-four consecutive patients referred to our Unit for suspected GERD were recruited for the study. All patients underwent esophageal pH-metric recording. For those with a positive test, C13 urea breath test was then performed to assess the H. pylori status. GERD patients were stratified according to the quality of their symptoms and classified as typical, if affected by heartburn and regurgitation, and atypical if complaining of chest pain, respiratory and ears, nose, and throat features. H. pylori-negative patients were also asked whether they had a previous diagnosis of H. pylori infection. If a positive response was given, on the basis of the time period after successful eradication, patients were considered as "eradicated" (E) if H. pylori eradication occurred more than six months earlier or "recently eradicated" if the therapy had been administered within the last six months. Patients without history of infection were identified as "negative" (N). χ (2) test was performed by combining the clinical aspects with the H. pylori status. one hundred and twenty-nine of the 144 patients, including 44 H. pylori-positive and 85 H. pylori-negative (41 negative, 21 recently eradicated, 23 eradicated more than 6 mo before), were eligible for the analysis. No difference has been found between H. pylori status and either the number of reflux episodes (138 ± 23 vs 146 ± 36, respectively, P = 0.2, not significant) or the percentage of time with pH values < 4 (6.8 ± 1.2 vs 7.4 ± 2.1, respectively, P = 0.3, not significant). The distribution of symptoms was as follows: 13 typical (30%) and 31 atypical (70%) among the 44 H. pylori-positive cases; 44 typical (52%) and 41 atypical (48%) among the 85 H. pylori-negative cases, (P = 0.017 vs H. pylori+; OR = 2.55, 95%CI: 1.17-5.55). Furthermore

High prevalence of Mycobacterium tuberculosis mixed infection in the capital of moderate tuberculosis incidence country.

PubMed

Hajimiri, Elahe Sadat; Masoomi, Morteza; Ebrahimzadeh, Nayereh; Fateh, Abolfazl; Hadizadeh Tasbiti, Alireza; Rahimi Jamnani, Fatemeh; Bahrmand, Ahmad Reza; Mirsaeidi, Mehdi; Vaziri, Farzam; Siadat, Seyed Davar

2016-04-01

Recent studies using molecular epidemiological techniques have demonstrated mixed infection with multiple strains of Mycobacterium tuberculosis especially in countries with high tuberculosis (TB) burden. We aimed to determine the prevalence of mixed infection among patients with TB in the capital of Iran as a country with moderate incidence rate. Samples were collected randomly from January 2011 to December 2013 in Tehran, capital of Iran. A total of 75 M. tuberculosis isolates were genotyped by 24 loci mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-VNTR) for screening the mixed infection. Twenty patients (20/75) were identified with mixed infection, and the estimated rate of mixed infection was 26.6%. Thirteen out of the 24 loci were able to detect the mixed infection in our study. Mixed infections occur at high prevalence among studied Iranian TB patients. Further research is inevitable to evaluate the association of mixed infection and disease progression and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of loci associated with susceptibility to mycobacterium avium subspecies paratuberculosis (Map) tissue infection in cattle

USDA-ARS?s Scientific Manuscript database

Johne’s disease is a contagious bacterial infection of cattle caused by Mycobacterium avium ssp. paratuberculosis (Map). A previous genome-wide association analysis (GWAA) in Holstein cattle identified QTL on BTA3 and BTA9 that were highly associated (P < 5 × 10-7) and on BTA1, BTA16, and BTA21 that...

Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery.

PubMed

Kohler, Philipp; Kuster, Stefan P; Bloemberg, Guido; Schulthess, Bettina; Frank, Michelle; Tanner, Felix C; Rössle, Matthias; Böni, Christian; Falk, Volkmar; Wilhelm, Markus J; Sommerstein, Rami; Achermann, Yvonne; Ten Oever, Jaap; Debast, Sylvia B; Wolfhagen, Maurice J H M; Brandon Bravo Bruinsma, George J; Vos, Margreet C; Bogers, Ad; Serr, Annerose; Beyersdorf, Friedhelm; Sax, Hugo; Böttger, Erik C; Weber, Rainer; van Ingen, Jakko; Wagner, Dirk; Hasse, Barbara

2015-10-21

We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Isolation of Mycobacterium avium subsp paratuberculosis (Map) from feral cats on a dairy farm with Map-infected cattle.

PubMed

Palmer, Mitchell V; Stoffregen, William C; Carpenter, Jeremy G; Stabel, Judith R

2005-07-01

Paratuberculosis is an economically important disease of dairy cattle caused by Mycobacterium avium subsp. paratuberculosis (Map). The role of nonruminant, nondomestic animals in the epidemiology of paratuberculosis in cattle is unclear. To examine nonruminant, nondomestic animals for the presence of Map, 25 feral cats, nine mice (species unknown), eight rabbits (Sylvilagus floridanus), six raccoons (Procyon lotor), and three opossums (Didelphis virginiana) were collected from a mid-western dairy with known Map-infected cattle. Mycobacterium avium subsp. paratuberculosis was isolated from the mesenteric lymph node from seven of 25 (28%) feral cats. Ileum was culture-positive for three of these seven cats, and an isolation of Map was also made from the ileum of one of nine (11%) mice. Tissue samples from other species were negative as determined by Map culture; microscopic lesions consistent with paratuberculosis were not seen in any animal. Restriction fragment polymorphism analysis of isolates from cats and dairy cattle suggest interspecies transmission. The means by which interspecies transmission occurred may be through ingestion of Map-contaminated feces or waste milk or through ingestion of Map-infected prey. Shedding of Map from infected cats was not evaluated. The epidemiologic role of Map-infected feral cats on dairy farms requires further investigation.

A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis

ClinicalTrials.gov

2017-10-12

Lung Diseases; Pulmonary Disease; Cystic Fibrosis; Cystic Fibrosis Lung; Cystic Fibrosis Pulmonary Exacerbation; Cystic Fibrosis With Exacerbation; Respiratory Tract Disease; Pulmonary Inflammation; Multi-antibiotic Resistance; Antibiotic Resistant Infection; Lung Infection; Lung Infection Pseudomonal; Lung; Infection, Atypical Mycobacterium; Burkholderia Infections; Burkholderia Cepacia Infection; Lung Inflammation

WC1+ gamma delta T cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis respond differentially to stimulation with PPD-J.

USDA-ARS?s Scientific Manuscript database

A role for gamma delta T cells in protection against mycobacterial infections including Johne’s disease (JD) has been suggested. In neonatal calves where the risk to infection with Mycobacterium avium subsp. paratuberculosis (MAP) is high, the majority of circulating CD3+ lymphocytes are gamma delta...

Notes from the Field: Mycobacterium abscessus Infections Among Patients of a Pediatric Dentistry Practice--Georgia, 2015.

PubMed

Peralta, Gianna; Tobin-D'Angelo, Melissa; Parham, Angie; Edison, Laura; Lorentzson, Lauren; Smith, Carol; Drenzek, Cherie

2016-04-08

On September 13, 2015, the Georgia Department of Public Health (DPH) was notified by hospital A of a cluster of pediatric Mycobacterium abscessus odontogenic infections. Hospital A had provided care for nine children who developed presumptive or confirmed M. abscessus infection after having a pulpotomy at pediatric dentistry practice A (dates of onset: July 23, 2014-September 4, 2015). During a pulpotomy procedure, decay and the diseased pulp are removed to preserve a deciduous tooth. DPH initiated an investigation to identify the outbreak source and recommend prevention and control measures.

A novel multi-antigen virally vectored vaccine against Mycobacterium avium subspecies paratuberculosis.

PubMed

Bull, Tim J; Gilbert, Sarah C; Sridhar, Saranya; Linedale, Richard; Dierkes, Nicola; Sidi-Boumedine, Karim; Hermon-Taylor, John

2007-11-28

Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice. A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly

Comparative Sigma Factor-mRNA Levels in Mycobacterium marinum under Stress Conditions and during Host Infection

PubMed Central

Pettersson, B. M. Fredrik; Das, Sarbashis; Behra, Phani Rama Krishna; Jordan, Heather R.; Ramesh, Malavika; Mallick, Amrita; Root, Kate M.; Cheramie, Martin N.; de la Cruz Melara, Irma; Small, Pamela L. C.; Dasgupta, Santanu; Ennis, Don G.; Kirsebom, Leif A.

2015-01-01

We have used RNASeq and qRT-PCR to study mRNA levels for all σ-factors in different Mycobacterium marinum strains under various growth and stress conditions. We also studied their levels in M. marinum from infected fish and mosquito larvae. The annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. Some were highly abundant such as sigA, sigB, sigC, sigD, sigE and sigH while others were not. The σ-factor mRNA profiles were similar after heat stress, during infection of fish and mosquito larvae. The similarity also applies to some of the known heat shock genes such as the α-crystallin gene. Therefore, it seems probable that the physiological state of M. marinum is similar when exposed to these different conditions. Moreover, the mosquito larvae data suggest that this is the state that the fish encounter when infected, at least with respect to σ-factor mRNA levels. Comparative genomic analysis of σ-factor gene localizations in three M. marinum strains and Mycobacterium tuberculosis H37Rv revealed chromosomal rearrangements that changed the localization of especially sigA, sigB, sigD, sigE, sigF and sigJ after the divergence of these two species. This may explain the variation in species-specific expression upon exposure to different growth conditions. PMID:26445268

An association between pulmonary Mycobacterium avium-intracellulare complex infections and biomarkers of Th2-type inflammation.

PubMed

Pfeffer, Paul E; Hopkins, Susan; Cropley, Ian; Lowe, David M; Lipman, Marc

2017-05-15

The rising incidence of pulmonary Mycobacterium avium-intracellulare complex (MAI) infection is unexplained but parallels the growing world-wide epidemic of allergic disease. We hypothesized an association between pulmonary MAI infection and Th2-type immune responses as seen in allergy. Biomarkers of patient Th2-type immune responses (peripheral blood eosinophil counts and serum IgE levels) were compared between patients with positive pulmonary samples for tuberculosis and non-tuberculous mycobacterial (NTM) infection. A further comparison of clinical characteristics, including respiratory co-morbidities, and biomarkers, was conducted between patients culturing MAI NTM and those culturing NTM other than MAI. Patients culturing NTM from pulmonary samples had significantly higher peripheral blood eosinophil levels than those culturing Mycobacterium tuberculosis. Furthermore, patients culturing MAI compared to those culturing NTM other than MAI had higher eosinophil counts (mean 0.29x10 9 /L vs 0.15x10 9 /L, p = 0.010) and IgE levels (geometric mean 138kU/L vs 47kU/L, p = 0.021). However there was no significant difference in the frequency of asthma between the two NTM groups. There is an association between biomarkers of Th2-type immune responses and pulmonary MAI. Prospective and translational research could identify the direction of causation; and so determine whether our finding may be utilized within future management strategies for MAI.

Prevention of Mycobacterium avium subsp. paratuberculosis Infection in BALB/c Mice by Feeding Lactobacillus acidophilus Strain NP-51

USDA-ARS?s Scientific Manuscript database

The immune responses of 390 BALB/c mice fed the probiotic Lactobacillus acidophilus strain NP51® and infected with Mycobacterium avium subspecies paratuberculosis (MAP) were evaluated in a 6-month trial. Mice were randomized to nine treatment groups fed either viable- or heat-killed NP51 and inocula...

The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico.

PubMed

Han, Xiang Y; Sizer, Kurt Clement; Velarde-Félix, Jesús S; Frias-Castro, Luis O; Vargas-Ocampo, Francisco

2012-08-01

Mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named Mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in Mexico. We sought to differentiate the leprosy agents among 120 Mexican patients with various clinical forms of leprosy and to compare their relative prevalences and disease features. Archived skin biopsy specimens from these patients were tested for both M. leprae and M. lepromatosis using polymerase chain reaction-based species-specific assays. Etiologic species were confirmed in 87 (72.5%) patients, of whom 55 were infected with M. lepromatosis, 18 with M. leprae, and 14 with both organisms. The endemic regions of each agent differed but overlapped. Patients with M. lepromatosis were younger and were distributed across more states; their clinical diagnoses included DLL (n = 13), lepromatous leprosy (LL) (n = 34), and eight other forms of leprosy. By contrast, the diagnoses of patients with M. leprae did not include DLL but did include LL (n = 15) and three other forms of leprosy. Thus, M. lepromatosis caused DLL specifically (P = 0.023). Patients with M. lepromatosis also showed more variable skin lesions; the extremities were the most common sites of biopsy in these patients. Finally, patients with dual infections manifested all clinical forms and accounted for 16.1% of all species-confirmed cases. Mycobacterium lepromatosis is another cause of leprosy and is probably more prevalent than M. leprae in Mexico. It mainly causes LL and also specifically DLL. Dual infections caused by both species may occur in endemic areas. © 2012 The International Society of Dermatology.

Granulomatous encephalomyelitis and intestinal ganglionitis in a spectacled Amazon parrot (Amazona albifrons) infected with Mycobacterium genavense.

PubMed

Gomez, G; Saggese, M D; Weeks, B R; Hoppes, S M; Porter, B F

2011-01-01

An approximately 30-year-old male spectacled Amazon parrot (Amazona albifrons) was presented with a 2-week history of ataxia, head shaking, weight loss and seizures. Gross findings on necropsy examination included atrophy of the musculature, ruffled feathers and minimal epicardial and abdominal fat. Microscopically, there were perivascular cuffs of macrophages with fewer lymphocytes in the grey and white matter of the brain and spinal cord. These lesions were accompanied by gliosis and mild vacuolation of the white matter. In the small intestine, up to 70% of the intestinal ganglia were effaced by infiltrates of macrophages and fewer lymphocytes. The intestinal lamina propria contained multiple inflammatory aggregates of a similar nature. Ziehl-Neelsen staining revealed the presence of numerous bacilli within the cytoplasm of macrophages in the central nervous system (CNS) and enteric ganglia. Amplification of the DNAJ gene confirmed a mycobacterial infection and subsequent polymerase chain reaction (PCR) using a species-specific primer confirmed the aetiology as Mycobacterium genavense. Infection of the CNS with Mycobacterium spp. is uncommon and has not been previously reported in a parrot. This case is unusual in that the organism exhibited tropism for neural tissue. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Phenotypic and genotypic characteristics of Mycobacterium kansasii strains isolated in Spain (2000-2003)].

PubMed

Jiménez-Pajares, María Soledad; Herrera, Laura; Valverde, Azucena; Saiz, Pilar; Sáez-Nieto, Juan Antonio

2005-05-01

Mycobacterium kansasii is an opportunistic pathogen that mainly causes pulmonary infections. This species accounted for 9.7% of Mycobacteria other than tuberculosis complex identified in the reference laboratory of the Spanish Centro Nacional de Microbiologia during the period of 2000-2003. In this study we analyzed the phenotypic and genotypic characteristics of 298 M. kansasii strains isolated over this 4-year period. The phenotypic characteristics were determined by conventional methods: biochemical testing, culture and morphological study. Genotypic characteristics were studied using PCR restriction fragment analysis of a fragment of the hsp65 gene and digestion with BstEII and HaeIII, according to the method of Telenti. Among the total of tested strains, 57.4% had the typical phenotypic characteristics described for M. kansasii. The rest had atypical patterns that we grouped into 17 biotypes. Strains belonging to six of the seven described genotypes were identified, with 86.6% of the strains falling into genotype I. Analysis of the phenotypic characteristics of M. kansasii showed a higher discrimination index for intraspecific differentiation than genotypic methods. Nevertheless, the high variability of phenotypic characteristics, some of which were very specific for the species (e.g., photochromogenicity), could complicate their identification. Hence both conventional and molecular methods should be used to accurately identify the atypical isolates.

Immunogenicity of PtpA secreted during Mycobacterium avium ssp. paratuberculosis infection in cattle.

PubMed

Bach, Eviatar; Raizman, Eran A; Vanderwal, Rich; Soto, Paolete; Chaffer, Marcelo; Keefe, Greg; Pogranichniy, Roman; Bach, Horacio

2018-04-01

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease. To survive within host macrophages, the pathogen secretes a battery of proteins to interfere with the immunological response of the host. One of these proteins is tyrosine phosphate A (PtpA), which has been identified as a secreted protein critical for survival of its close relative M. tuberculosis within infected macrophages. In this study, the immune response to recombinant PtpA used as an antigen was investigated in a cohort of ∼1000 cows infected with MAP compared to negative control animals using ELISA. The sera from MAP-infected cows had significantly higher levels of antibodies against PtpA when compared to uninfected cows. The data presented here indicate that the antibodies produced against PtpA are sensitive enough to detect infected animals before the appearance of the disease symptoms. The use of PtpA as an antigen can be developed as an early diagnostic test. Moreover, PtpA is a candidate antigen for detection of humoral immune responses in cows infected with MAP. Copyright © 2018 Elsevier B.V. All rights reserved.

The Global Reciprocal Reprogramming between Mycobacteriophage SWU1 and Mycobacterium Reveals the Molecular Strategy of Subversion and Promotion of Phage Infection

PubMed Central

Fan, Xiangyu; Duan, Xiangke; Tong, Yan; Huang, Qinqin; Zhou, Mingliang; Wang, Huan; Zeng, Lanying; Young, Ry F.; Xie, Jianping

2016-01-01

Bacteriophages are the viruses of bacteria, which have contributed extensively to our understanding of life and modern biology. The phage-mediated bacterial growth inhibition represents immense untapped source for novel antimicrobials. Insights into the interaction between mycobacteriophage and Mycobacterium host will inform better utilizing of mycobacteriophage. In this study, RNA sequencing technology (RNA-seq) was used to explore the global response of Mycobacterium smegmatis mc2155 at an early phase of infection with mycobacteriophage SWU1, key host metabolic processes of M. smegmatis mc2155 shut off by SWU1, and the responsible phage proteins. The results of RNA-seq were confirmed by Real-time PCR and functional assay. 1174 genes of M. smegmatis mc2155 (16.9% of the entire encoding capacity) were differentially regulated by phage infection. These genes belong to six functional categories: (i) signal transduction, (ii) cell energetics, (iii) cell wall biosynthesis, (iv) DNA, RNA, and protein biosynthesis, (v) iron uptake, (vi) central metabolism. The transcription patterns of phage SWU1 were also characterized. This study provided the first global glimpse of the reciprocal reprogramming between the mycobacteriophage and Mycobacterium host. PMID:26858712

Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection.

PubMed Central

Segueni, Noria; Benmerzoug, Sulayman; Rose, Stéphanie; Gauthier, Amandine; Bourigault, Marie-Laure; Reverchon, Flora; Philippeau, Amandine; Erard, François; Le Bert, Marc; Bouscayrol, Hélène; Wachter, Thierry; Garcia, Irène; Kollias, George; Jacobs, Muazzam; Ryffel, Bernhard; Quesniaux, Valerie F.J.

2016-01-01

TNF is crucial for controlling Mycobacterium tuberculosis infection and understanding how will help immunomodulating the host response. Here we assessed the contribution of TNFR1 pathway from innate myeloid versus T cells. We first established the prominent role of TNFR1 in haematopoietic cells for controlling M. tuberculosis in TNFR1 KO chimera mice. Further, absence of TNFR1 specifically on myeloid cells (M-TNFR1 KO) recapitulated the uncontrolled M. tuberculosis infection seen in fully TNFR1 deficient mice, with increased bacterial burden, exacerbated lung inflammation, and rapid death. Pulmonary IL-12p40 over-expression was attributed to a prominent CD11b+ Gr1high cell population in infected M-TNFR1 KO mice. By contrast, absence of TNFR1 on T-cells did not compromise the control of M. tuberculosis infection over 6-months. Thus, the protective TNF/TNFR1 pathway essential for controlling primary M. tuberculosis infection depends on innate macrophage and neutrophil myeloid cells, while TNFR1 pathway in T cells is dispensable. PMID:26931771

Mycobacterium tuberculosis promotes genomic instability in macrophages

PubMed Central

Castro-Garza, Jorge; Luévano-Martínez, Miriam Lorena; Villarreal-Treviño, Licet; Gosálvez, Jaime; Fernández, José Luis; Dávila-Rodríguez, Martha Imelda; García-Vielma, Catalina; González-Hernández, Silvia; Cortés-Gutiérrez, Elva Irene

2018-01-01

BACKGROUND Mycobacterium tuberculosis is an intracellular pathogen, which may either block cellular defensive mechanisms and survive inside the host cell or induce cell death. Several studies are still exploring the mechanisms involved in these processes. OBJECTIVES To evaluate the genomic instability of M. tuberculosis-infected macrophages and compare it with that of uninfected macrophages. METHODS We analysed the possible variations in the genomic instability of Mycobacterium-infected macrophages using the DNA breakage detection fluorescence in situ hybridisation (DBD-FISH) technique with a whole human genome DNA probe. FINDINGS Quantitative image analyses showed a significant increase in DNA damage in infected macrophages as compared with uninfected cells. DNA breaks were localised in nuclear membrane blebs, as confirmed with DNA fragmentation assay. Furthermore, a significant increase in micronuclei and nuclear abnormalities were observed in infected macrophages versus uninfected cells. MAIN CONCLUSIONS Genomic instability occurs during mycobacterial infection and these data may be seminal for future research on host cell DNA damage in M. tuberculosis infection. PMID:29412354

Mycobacterium tuberculosis promotes genomic instability in macrophages.

PubMed

Castro-Garza, Jorge; Luévano-Martínez, Miriam Lorena; Villarreal-Treviño, Licet; Gosálvez, Jaime; Fernández, José Luis; Dávila-Rodríguez, Martha Imelda; García-Vielma, Catalina; González-Hernández, Silvia; Cortés-Gutiérrez, Elva Irene

2018-03-01

Mycobacterium tuberculosis is an intracellular pathogen, which may either block cellular defensive mechanisms and survive inside the host cell or induce cell death. Several studies are still exploring the mechanisms involved in these processes. To evaluate the genomic instability of M. tuberculosis-infected macrophages and compare it with that of uninfected macrophages. We analysed the possible variations in the genomic instability of Mycobacterium-infected macrophages using the DNA breakage detection fluorescence in situ hybridisation (DBD-FISH) technique with a whole human genome DNA probe. Quantitative image analyses showed a significant increase in DNA damage in infected macrophages as compared with uninfected cells. DNA breaks were localised in nuclear membrane blebs, as confirmed with DNA fragmentation assay. Furthermore, a significant increase in micronuclei and nuclear abnormalities were observed in infected macrophages versus uninfected cells. Genomic instability occurs during mycobacterial infection and these data may be seminal for future research on host cell DNA damage in M. tuberculosis infection.

Effectiveness of purified methylene blue in an experimental model of Mycobacterium ulcerans infection.

PubMed

Tian, Roger B D; Asmar, Shady; Napez, Claude; Lépidi, Hubert; Drancourt, Michel

2017-03-01

Mycobacterium ulcerans is responsible for Buruli ulcer, characterised by extensive, disabling ulcers. Standard treatment combining rifampicin and streptomycin exposes patients to toxicity and daily painful injections. In this study, the in vitro susceptibilities of 3 M. ulcerans strains, 1 Mycobacterium marinum strain and 18 strains representative of eleven other Mycobacterium species and subspecies to methylene blue were determined. Whilst growth of M. ulcerans was inhibited by 0.0125 g/L methylene blue, growth of all other tested strains was not inhibited by 1 g/L methylene blue. The effectiveness of methylene blue in a murine model of M. ulcerans infection was then tested. Topical treatment by brushing a methylene blue solution on the skin lesion, systemic treatment by intraperitoneal injection of methylene blue, and a combined treatment (topical and systemic) were tested. The three treatment groups exhibited a significantly lower clinical score compared with the non-treated control group (P <0.05). Moreover, subcutaneous nodules were significantly smaller in the systemic treatment group (excluding males) (3 ± 0.7 mm) compared with the other groups (P <0.05). The M. ulcerans insertion sequence IS2404 and the KR-B gene were detected in all challenged mice, but not in negative controls. The density of M. ulcerans (mycobacteria/cell) was significantly lower in the combined treatment group compared with the other groups. These data provide evidence for the effectiveness of purified methylene blue against the initial stage of Buruli ulcer. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

[Identification and drug susceptibility testing of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis].

PubMed

Li, W B; Ji, L Y; Xu, D L; Liu, H C; Zhao, X Q; Wu, Y M; Wan, K L

2018-05-10

Objective: To understand the etiological characteristics and drug susceptibility of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis and provide evidence for the prevention and control of infectious mastitis in cows. Methods: The milk sample was collected from a cow with mastitis, which was pretreated with 4 % NaOH and inoculated with L-J medium for Mycobacterium isolation. The positive cultures were initially identified by acid-fast staining and multi-loci PCR, then Mycobacterium species was identified by the multiple loci sequence analysis (MLSA) with 16S rRNA , hsp65 , ITS and SodA genes. The drug sensitivity of the isolates to 27 antibiotics was tested by alamar blue assay. Results: Two anti-acid stain positive strains were isolated from the milk of a cow with mastitis, which were identified as non- tuberculosis mycobacterium by multi-loci PCR, and multi-loci nucleic acid sequence analysis indicated that one strain was Mycobacterium thermoresistibile and another one was Mycobacterium elephantis . The results of the drug susceptibility test showed that the two strains were resistant to most antibiotics, including rifampicin and isoniazid, but they were sensitive to amikacin, moxifloxacin, levofloxacin, ethambutol, streptomycin, tobramycin, ciprofloxacin and linezolid. Conclusions: Mycobacterium thermoresistibile and Mycobacterium elephantis were isolated in a cow with mastitis and the drug susceptibility spectrum of the pathogens were unique. The results of the study can be used as reference for the prevention and control the infection in cows.

Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

Infection of the host with Mycobacterium avium subsp. paratuberculosis (MAP) results in a chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from asymptomatic subclinical disease state to advanced clinical disease are not fully under...

Detection of viruses and atypical bacteria associated with acute respiratory infection of children in Hubei, China.

PubMed

Wu, Zegang; Li, Yan; Gu, Jian; Zheng, Hongyun; Tong, Yongqing; Wu, Qing

2014-02-01

Acute respiratory infection is the major cause of disease and death in children, particularly in developing countries. However, the spectrum of pathogenic viruses and atypical bacteria that exist in many of these countries remains incompletely characterized. The aim of this study was to examine the spectrum of pathogenic viruses and atypical bacteria associated with acute respiratory infection in children under the age of 16. A total of 10 435 serum sera specimens were collected from hospitalized children presenting with acute respiratory infection symptoms. Indirect immunofluorescence assays were performed to detect immunoglobulin M antibodies against nine common pathogens: mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila, coxiella burnetii and chamydophila pneumonia. Of the 10 435 specimens examined, 7046 tested positive for at least one pathogen. Among all of the tested pathogens, mycoplasma pneumonia had the highest detection rate (56.9%). Influenza virus A and influenza virus B epidemics occurred during both winter and summer. The detection rate of respiratory syncytial virus and adenovirus was higher in spring. Cases of mixed infection were more complex: 4136 specimens (39.6%) tested positive for ≥2 pathogens. There were statistically significant difference in detection rates of mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila and chamydophila pneumonia among different age groups (P < 0.05). The most common pathogens causing acute respiratory infection among children in Hubei of China were mycoplasma pneumonia, influenza virus B and respiratory syncytial virus. The detection rates for each pathogen displayed specific seasonal and age group variations. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

The effect of Mycobacterium avium ssp. paratuberculosis infection on clinical mastitis occurrence in dairy cows.

PubMed

Rossi, G; Grohn, Y T; Schukken, Y H; Smith, R L

2017-09-01

Endemic diseases can be counted among the most serious sources of losses for livestock production. In dairy farms in particular, one of the most common diseases is Johne's disease, caused by Mycobacterium avium ssp. paratuberculosis (MAP). Infection with MAP causes direct costs because it affects milk production, but it has also been suspected to increase the risk of clinical mastitis (CM) among infected animals. This might contribute to further costs for farmers. We asked whether MAP infection represents a risk factor for CM and, in particular, whether CM occurrences were more common in MAP-infected animals. Our results, obtained by survival analysis, suggest that MAP-infected cows had an increased probability of experiencing CM during lactation. These results highlight the need to account for the interplay of infectious diseases and other health conditions in economic and epidemiological modeling. In this case, accounting for MAP-infected cows having an increased CM occurrence might have nonnegligible effects on the estimated benefit of MAP control. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

PubMed Central

Denkinger, Claudia M.; Kik, Sandra V.; Rangaka, Molebogeng X.; Zwerling, Alice; Oxlade, Olivia; Metcalfe, John Z.; Cattamanchi, Adithya; Dowdy, David W.; Dheda, Keertan; Banaei, Niaz

2014-01-01

SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers. PMID:24396134

Heparin-Binding Haemagglutinin, a New Tool for the Detection of Latent Mycobacterium tuberculosis Infection in Hemodialysis Patients

PubMed Central

Dessein, Rodrigue; Corbière, Véronique; Nortier, Joëlle; Dratwa, Max; Gastaldello, Karine; Pozdzik, Agnieszka; Lecher, Sophie; Grandbastien, Bruno; Locht, Camille; Mascart, Françoise

2013-01-01

Background Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more sensitive than tuberculin skin tests for the detection of infected individuals in dialysis patients. Methods On 143 dialysis patients prospectively enrolled, we compared the results from the QuantiFERON®-TB Gold assay (QFT), to those of an IGRA in response to in vitro stimulation of circulating mononuclear cells with the mycobacterial latency antigen Heparin-Binding Haemagglutinin purified from Mycobacterium bovis BCG (native HBHA, nHBHA). Results Seven patients had a past history of active TB and 1 had an undetermined result with both IGRAs. Among the other 135 patients, 94 had concordant results with the QFT and nHBHA-IGRA, 40.0% being negative and therefore not latently infected, and 29.6% being positive and thus LTBI. Discrepant results between these tests were found for 36 patients positive only with the nHBHA-IGRA and 5 only with the QFT. Conclusions The nHBHA-IGRA is more sensitive than the QFT for the detection of LTBI dialysis patients, and follow-up of the patients will allow us to define the clinical significance of discrepant results between the nHBHA-IGRA and the QFT. PMID:23940693

Prevalence of latent Mycobacterium tuberculosis infection in prisoners

PubMed Central

de Navarro, Pedro Daibert; de Almeida, Isabela Neves; Kritski, Afrânio Lineu; Ceccato, Maria das Graças; Maciel, Mônica Maria Delgado; Carvalho, Wânia da Silva; de Miranda, Silvana Spindola

2016-01-01

ABSTRACT Objective: To determine the prevalence of and the factors associated with latent Mycobacterium tuberculosis infection (LTBI) in prisoners in the state of Minas Gerais, Brazil. Methods: This was a cross-sectional cohort study conducted in two prisons in Minas Gerais. Tuberculin skin tests were performed in the individuals who agreed to participate in the study. Results: A total of 1,120 individuals were selected for inclusion in this study. The prevalence of LTBI was 25.2%. In the multivariate analysis, LTBI was associated with self-reported contact with active tuberculosis patients within prisons (adjusted OR = 1.51; 95% CI: 1.05-2.18) and use of inhaled drugs (adjusted OR = 1.48; 95% CI: 1.03-2.13). Respiratory symptoms were identified in 131 (11.7%) of the participants. Serological testing for HIV was performed in 940 (83.9%) of the participants, and the result was positive in 5 (0.5%). Two cases of active tuberculosis were identified during the study period. Conclusions: Within the prisons under study, the prevalence of LTBI was high. In addition, LTBI was associated with self-reported contact with active tuberculosis patients and with the use of inhaled drugs. Our findings demonstrate that it is necessary to improve the conditions in prisons, as well as to introduce strategies, such as chest X-ray screening, in order to detect tuberculosis cases and, consequently, reduce M. tuberculosis infection within the prison system. PMID:27812634

Influence of vehicles used for oral dosing of test molecules on the progression of Mycobacterium tuberculosis infection in mice.

PubMed

Singh, Shubhra; Dwivedi, Richa; Chaturvedi, Vinita

2012-11-01

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters.

Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

PubMed

Scordo, Julia M; Knoell, Daren L; Torrelles, Jordi B

2016-01-01

Tuberculosis (TB) is a disease that kills one person every 18 s. TB remains a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure, which influence the extent of infection. We further discuss how the M.tb-alveolar epithelium interaction instigates cell-to-cell crosstalk that regulates the immune balance between a proinflammatory and an immunoregulatory state, thereby prohibiting or allowing the establishment of infection. We propose that consideration of alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. © 2015 S. Karger AG, Basel.

Alveolar epithelial cells in Mycobacterium tuberculosis infection: Active Players or Innocent Bystanders

PubMed Central

Scordo, Julia M.; Knoell, Daren L.; Torrelles, Jordi B.

2015-01-01

Tuberculosis (TB) is a disease that kills one person every 18 seconds. TB remains a global threat due to the emergence of drug resistance Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following sero-conversion and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure that influence the extent of infection. We further discuss how the M.tb-alveolar epithelia interaction instigate cell to cell crosstalk that regulates immune balance between a pro-inflammatory or immunoregulatory state thereby prohibiting or allowing the establishment of infection. We propose that consideration of the alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. PMID:26384325

Experimental colitis is exacerbated by concomitant infection with Mycobacterium avium ssp. paratuberculosis.

PubMed

Suwandi, Abdulhadi; Bargen, Imke; Roy, Bishnudeo; Pils, Marina C; Krey, Martina; Zur Lage, Susanne; Basler, Tina; Rohde, Manfred; Falk, Christine S; Hornef, Mathias W; Goethe, Ralph; Weiss, Siegfried

2014-11-01

Crohn's disease (CD) is a chronic inflammatory disorder of the human gastrointestinal tract. Although genetic, immunological, environmental, and bacterial factors have been implicated, the pathogenesis is incompletely understood. The histopathological appearance of CD strikingly resembles Johne's disease, a ruminant inflammatory bowel disease, caused by Mycobacterium avium ssp. paratuberculosis (MAP), but a causative role of MAP in CD has not been established. In this work, we hypothesized that MAP might exacerbate an already existing intestinal disease. We combined dextran sulfate sodium (DSS)-induced colitis with MAP infection in mice and monitored the immune response and bacterial count in different organs. An increased size of liver and spleen was observed in DSS-treated and MAP-infected animals (DSS + MAP) as compared with DSS-treated uninfected (DSS + PBS) mice. Similarly, DSS treatment increased the number and size of MAP-induced liver granulomas and enhanced the MAP counts in enteric tissue. MAP infection in turn delayed the mucosal healing of DSS-induced tissue damage. Finally, high numbers of MAP were found in mesenteric fat tissue causing large granuloma and necrotic regions. Taken together, we present an in vivo model to study the role of MAP infection in CD. Our results confirm the hypothesis that MAP is able to exacerbate existing intestinal inflammation.

Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data

NASA Astrophysics Data System (ADS)

Magombedze, Gesham; Shiri, Tinevimbo; Eda, Shigetoshi; Stabel, Judy R.

2017-03-01

Available diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-γ, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-γ/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.

[Origin and development of RUTI, a new therapeutic vaccine against Mycobacterium tuberculosis infection].

PubMed

Cardona, P J; Amat, I

2006-01-01

This article reviews the pathophysiology of the latent form of Mycobacterium tuberculosis along with its natural history and progression in infected tissues. The proposed hypotheses regarding the relationship between M tuberculosis and the associated immune response, the cause of granuloma necrosis, the tolerance of a certain concentration of the bacillus in host tissues, the constant turnover of cells in the lung, and the effect of chemotherapy form the basis for the design of the therapeutic vaccine RUTI against latent M tuberculosis infection. This vaccine is generated from detoxified M tuberculosis cell fragments that facilitate a balanced T helper (Th) 1/Th2/Th3 response to a wide range of antigens along with intense antibody production. Treatment with RUTI following chemotherapy has been demonstrated to be effective in experimental models in mice and guinea pigs and does not exhibit toxicity.

Draft Genome Sequence of Mycobacterium asiaticum Strain DSM 44297.

PubMed

Croce, Olivier; Robert, Catherine; Raoult, Didier; Drancourt, Michel

2014-04-17

We report the draft genome sequence of Mycobacterium asiaticum strain DSM 44297, a tropical mycobacterium seldom responsible for human infection. The genome of M. asiaticum has a size of 5,935,986 bp, with a 66.03% G+C content, encoding 5,591 proteins and 81 RNAs.

Use of the Intradermal Tuberculin Test in a Herd of Captive Elk (Cervus elaphus nelsoni) Naturally Infected with Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Tuberculosis of captive Cervidae, caused by Mycobacterium bovis, attracted attention in 1991 in the United States when investigations, prompted by the identification of a tuberculous elk (Cervus elaphus nelsoni) in Canada, revealed infected captive elk herds in 8 different states. Based on methods u...

Drug susceptibility testing of Mycobacterium Avium subsp. Avium isolates from naturally infected domestic pigeons to avian tuberculosis.

PubMed

Parvandar, Kaveh; Mayahi, Mansour; Mosavari, Nader; Pajoohi, Reza Aref

2016-12-01

Avian tuberculosis is one of the most important infections affecting most species of birds. Several mycobacterial species have been identified causing avian tuberculosis, and the organisms confirmed most frequently are Mycobacterium avium and Mycobacterium genavense. Any species of birds can be infected with M. avium. Generally, domesticated fowl or captive wild birds are affected more frequently than those living in the wild. M. avium can not only infect all species of birds, but can also infect some domesticated mammals to cause disease, usually with localized lesion. In immunocompetent individuals, M. avium complex isolates produce localized soft tissue infections, including chronic pulmonary infections in the elderly and cervical lymphadenitis in children, but rarely any disseminated disease. In patients infected with HIV and AIDS or in other immunocompromised individuals, M. avium complex isolates frequently cause severe systemic infections. The importance of avian tuberculosis and the risk of its zoonotic spread motivated our interest to determine the drug susceptibility testing of M. avium subsp. avium isolates from naturally infected domestic pigeons to avian tuberculosis. Based on their clinical signs, 80 pigeons suspected with avian tuberculosis were subjected to the study. Out of the 51 identified isolates, 20 M. avium subsp. avium were subjected to the test. Drug susceptibly testing was performed according to the guidelines by Centers for Disease Control and Prevention and using proportional method. In the drug susceptibility testing, all isolates were resistant to streptomycin, kanamycin, ethionamide, and thiophene carboxylic acid hydrazide. Additionally, 3, 2, and 1 isolates were susceptible to isoniazid, rifampin, and ethambutol, respectively. To date, no study has documented the drug susceptibility testing of M. avium isolates from infected birds to avian tuberculosis. Pigeons are extensively kept in urban and rural areas for homing and racing

Mycobacterium avium-intracellulare: a rare cause of subacromial bursitis.

PubMed

Sinha, Raj; Tuckett, John; Hide, Geoff; Dildey, Petra; Karsandas, Alvin

2015-01-01

Septic subacromial bursitis is an uncommon disorder with only a few reported cases in the literature. The most common causative organism is Staphylococcus aureus. We report the case of a 61-year-old female with a septic subacromial bursitis where the causative organism was found to be Mycobacterium avium-intracellulare (MAI). The diagnosis was only made following a biopsy, and we use this case to highlight the importance of recognising the need to consider a biopsy and aspiration in atypical situations.

Generation of transgenic cattle expressing human β-defensin 3 as an approach to reducing susceptibility to Mycobacterium bovis infection.

PubMed

Su, Feng; Wang, Yongsheng; Liu, Guanghui; Ru, Kun; Liu, Xin; Yu, Yuan; Liu, Jun; Wu, Yongyan; Quan, Fusheng; Guo, Zekun; Zhang, Yong

2016-03-01

Bovine tuberculosis results from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis family. Worldwide, M. bovis infections result in economic losses in the livestock industry; cattle production is especially hard-hit by this disease. Generating M. bovis-resistant cattle may potentially mitigate the impact of this disease by reducing M. bovis infections. In this study, we used transgenic somatic cell nuclear transfer to generate cattle expressing the gene encoding human β-defensin 3 (HBD3), which confers resistance to mycobacteria in vitro. We first generated alveolar epithelial cells expressing HBD3 under the control of the bovine MUC1 promoter, and confirmed that these cells secreted HBD3 and possessed anti-mycobacterial capacity. We then generated and identified transgenic cattle by somatic cell nuclear transfer. The cleavage and blastocyst formation rates of genetically modified embryos provided evidence that monoclonal transgenic bovine fetal fibroblast cells have an integral reprogramming ability that is similar to that of normal cells. Five genetically modified cows were generated, and their anti-mycobacterial capacities were evaluated. Alveolar epithelial cells and macrophages from these cattle expressed higher levels of HBD3 protein compared with non-transgenic cells and possessed effective anti-mycobacterial capacity. These results suggest that the overall risk of M. bovis infection in transgenic cattle is efficiently reduced, and support the development of genetically modified animals as an effective tool to reduce M. bovis infection. © 2016 Federation of European Biochemical Societies.

Impact of Euro-American sublineages of Mycobacterium tuberculosis on new infections among named contacts.

PubMed

Feng, J-Y; Jarlsberg, L G; Rose, J; Grinsdale, J A; Janes, M; Higashi, J; Osmond, D H; Nahid, P; Hopewell, P C; Kato-Maeda, M

2017-05-01

The impact of demographic, clinical, and bacterial factors on new infection by Euro-American lineage Mycobacterium tuberculosis among contacts of patients with tuberculosis (TB) has not been evaluated. To describe the risk factors for new infection by Euro-American M. tuberculosis sublineages in San Francisco, California. We included contacts of patients with TB due to Euro-American M. tuberculosis. Sublineages were determined by large-sequence polymorphisms. We used tuberculin skin testing or QuantiFERON®-TB Gold In-Tube to identify contacts with new infection. Regression models with generalized estimating equations were used to determine the risk factors for new infection. We included 1488 contacts from 134 patients with TB. There were 79 (5.3%) contacts with new infection. In adjusted analyses, contacts of patients with TB due to region of difference 219 M. tuberculosis sublineage were less likely to have new infection (OR 0.23, 95%CI 0.06-0.84) than those with other sublineages. Other risk factors for new infection were contacts exposed to more than one patient with TB, contacts exposed for 30 days, or contacts with a history of smoking or excessive alcohol consumption. In addition to well-known exposure and clinical characteristics, bacterial characteristics independently contribute to the transmissibility of TB in San Francisco.

A Negative Feedback Loop Between Autophagy and Immune Responses in Mycobacterium leprae Infection.

PubMed

Ma, Yuelong; Zhang, Li; Lu, Jie; Shui, Tiejun; Chen, Jia; Yang, Jun; Yuan, Joanna; Liu, Yeqiang; Yang, Degang

2017-01-01

The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level. However, macrophages with high autophagy levels preferentially expressed lower levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor-α, and preferentially primed anti-inflammatory T cells responses, characterized by high IL-10 and low interferon-γ, granzyme B, and perforin responses. These anti-inflammatory T cells could suppress further induction of autophagy, leading to improved survival of intracellular M. leprae in infected macrophages. Therefore, these data demonstrated that although autophagy had a role in eliminating intracellular pathogens, the induction of autophagy resulted in anti-inflammatory immune responses, which suppressed autophagy in a negative feedback loop and allowed the persistence of M. leprae.

MULTIMODAL IMAGING OF CHOROIDAL LESIONS IN DISSEMINATED MYCOBACTERIUM CHIMAERA INFECTION AFTER CARDIOTHORACIC SURGERY.

PubMed

Böni, Christian; Al-Sheikh, Mayss; Hasse, Barbara; Eberhard, Roman; Kohler, Philipp; Hasler, Pascal; Erb, Stefan; Hoffmann, Matthias; Barthelmes, Daniel; Zweifel, Sandrine A

2017-12-04

To explore morphologic characteristics of choroidal lesions in patients with disseminated Mycobacterium chimaera infection subsequent to open-heart surgery. Nine patients (18 eyes) with systemic M. chimaera infection were reviewed. Activity of choroidal lesions were evaluated using biomicroscopy, fundus autofluorescence, enhanced depth imaging optical coherence tomography, fluorescein angiography/indocyanine green angiography, and optical coherence tomography angiography. Relationships of choroidal findings to systemic disease activity were sought. All 9 male patients, aged between 49 and 66 years, were diagnosed with endocarditis and/or aortic graft infection. Mean follow-up was 17.6 months. Four patients had only inactive lesions (mild disease). In all five patients (10 eyes) with progressive ocular disease, indocyanine green angiography was superior to other tests for revealing new lesions and active lesions correlated with hyporeflective choroidal areas on enhanced depth imaging optical coherence tomography. One eye with a large choroidal granuloma developed choroidal neovascularization. Optical coherence tomography angiography showed areas with reduced perfusion at the inner choroid. All 5 patients with progressive ocular disease had evidence of systemic disease activity within ±6 weeks' duration. Choroidal manifestation of disseminated M. chimaera infection indicates systemic disease activity. Multimodal imaging is suitable to recognize progressive ocular disease. We propose ophthalmologic screening examinations for patients with M. chimaera infection.

ISONIAZID AND RIFAMPIN PHARMACOKINETICS IN TWO ASIAN ELEPHANTS (ELEPHAS MAXIMUS) INFECTED WITH MYCOBACTERIUM TUBERCULOSIS.

PubMed

Egelund, Eric F; Isaza, Ramiro; Alsultan, Abdullah; Peloquin, Charles A

2016-09-01

This report describes the pharmacokinetic profiles of chronically administered oral isoniazid and rifampin in one adult male and one adult female Asian elephant ( Elephas maximus ) that were asymptomatically infected with Mycobacterium tuberculosis . Rifampin's half-life was reduced when compared to previous single-dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both elephants experienced delayed absorption of isoniazid and rifampin as compared to previous pharmacokinetic studies in this species. The altered pharmacokinetics of both drugs in repeated-dosing clinical situations underscores the need for individual therapeutic drug monitoring for tuberculosis treatment.

Mycobacterium tuberculosis and non-tuberculous mycobacteria isolates from HIV-infected patients in Guangxi, China.

PubMed

Lan, R; Yang, C; Lan, L; Ou, J; Qiao, K; Liu, F; Gao, Q

2011-12-01

Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected persons. The prevalence of infection with Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) in HIV-infected patients in China is unknown. To estimate the prevalence of M. tuberculosis and NTM in HIV-infected patients in Guangxi Province, determine their drug resistance profiles, and evaluate the genotype patterns of M. tuberculosis strains. Samples were collected from two HIV designated hospitals in Guangxi Province between 2005 and 2008. HIV-infected patients who were culture-positive for mycobacteria were included. Drug susceptibility testing was performed for mycobacterial isolates. NTM species was identified by sequencing, and M. tuberculosis isolates were genotyped using the variable number of tandem repeats method. M. tuberculosis and NTM were identified in respectively 117 (53%) and 102 (47%) HIV-infected patients. Drug resistance was found in 27% and multi-drug-resistant TB (MDR-TB) in 11% of the patients with TB. Previous treatment for TB was significantly associated with MDR-TB. Twenty (17%) TB patients belonged to eight VNTR-defined clusters. The high frequency of NTM among HIV-infected patients raises concerns about accurate species identification before the determination of appropriate treatment. The potential for TB transmission exists among HIV-infected patients. Intensified screening and effective treatment of TB-HIV co-infected patients is urgently needed.

Atypical necrotizing encephalitis associated with systemic canine distemper virus infection in pups

PubMed Central

Amude, Alexandre Mendes; Alfieri, Amauri Alcindo; Beloni, Suely Nunes Esteves; Alfieri, Alice Fernandes

2011-01-01

This report describes the naturally occurring atypical neuropathological manifestation of systemic canine distemper virus (CDV) infection in two 16-day-old Pit Bull pups. CDV-induced changes affected the gray and white matter of the forebrain while sparing the hindbrain. Histologically, there was necrosis with destruction of the nervous parenchyma due to an influx of inflammatory and reactive cells associated with eosinophilic intranuclear inclusion bodies within glial cells. Positive immunoreactivity against CDV antigens was predominantly observed within astrocytes and neurons. RT-PCR was used to amplify CDV-specific amplicons from brain fragments. These findings suggest the participation of CDV in the etiopathogenesis of these lesions. PMID:22122909

Chronic infection with Mycobacterium lepraemurium induces alterations in the hippocampus associated with memory loss.

PubMed

Becerril-Villanueva, Enrique; Ponce-Regalado, María Dolores; Pérez-Sánchez, Gilberto; Salazar-Juárez, Alberto; Arreola, Rodrigo; Álvarez-Sánchez, María Elizbeth; Juárez-Ortega, Mario; Falfán-Valencia, Ramcés; Hernández-Pando, Rogelio; Morales-Montor, Jorge; Pavón, Lenin; Rojas-Espinosa, Oscar

2018-06-13

Murine leprosy, caused by Mycobacterium lepraemurium (MLM), is a chronic disease that closely resembles human leprosy. Even though this disease does not directly involve the nervous system, we investigated a possible effect on working memory during this chronic infection in Balb/c mice. We evaluated alterations in the dorsal region of the hippocampus and measured peripheral levels of cytokines at 40, 80, and 120 days post-infection. To evaluate working memory, we used the T-maze while a morphometric analysis was conducted in the hippocampus regions CA1, CA2, CA3, and dentate gyrus (DG) to measure morphological changes. In addition, a neurochemical analysis was performed by HPLC. Our results show that, at 40 days post-infection, there was an increase in the bacillary load in the liver and spleen associated to increased levels of IL-4, working memory deterioration, and changes in hippocampal morphology, including degeneration in the four subregions analyzed. Also, we found a decrease in neurotransmitter levels at the same time of infection. Although MLM does not directly infect the nervous system, these findings suggest a possible functional link between the immune system and the central nervous system.

Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice

PubMed Central

Singh, Shubhra; Dwivedi, Richa

2012-01-01

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters. PMID:22926571

Multisite Infection with Mycobacterium abscessus after Replacement of Breast Implants and Gluteal Lipofilling

PubMed Central

Rüegg, Eva; Cheretakis, Alexandre; Modarressi, Ali; Harbarth, Stephan; Pittet-Cuénod, Brigitte

2015-01-01

Introduction. Medical tourism for aesthetic surgery is popular. Nontuberculous mycobacteria (NTM) occasionally cause surgical-site infections. As NTM grow in biofilms, implantations of foreign bodies are at risk. Due to late manifestation, infections occur when patients are back home, where they must be managed properly. Case Report. A 39-year-old healthy female was referred for acute infection of the right gluteal area. Five months before, she had breast implants replacement, abdominal liposuction, and gluteal lipofilling in Mexico. Three months postoperatively, implants were removed for NTM-infection in Switzerland. Adequate antibiotic treatment was stopped after seven days for drug-related hepatitis. At entrance, gluteal puncture for bacterial analysis was performed. MRI showed large subcutaneous collection. Debridement under general anaesthesia was followed by open wound management. Total antibiotic treatment was 20 weeks. Methods. Bacterial analysis of periprosthetic and gluteal liquids included Gram-stain plus acid-fast stain, and aerobic, anaerobic and mycobacterial cultures.  Results. In periprosthetic fluid, Mycobacterium abscessus, Propionibacterium, and Staphylococcus epidermidis were identified. The same M. abscessus strain was found gluteally. The gluteal wound healed within six weeks. At ten months' follow-up, gluteal asymmetry persists for deep scarring. Conclusion. This case presents major complications of multisite aesthetic surgery. Surgical-site infections in context of medical tourism need appropriate bacteriological investigations, considering potential NTM-infections. PMID:25893122

A Rapid Method for Quantifying Viable Mycobacterium avium subsp. paratuberculosis in Cellular Infection Assays

PubMed Central

Pooley, Hannah B.; de Silva, Kumudika; Purdie, Auriol C.; Begg, Douglas J.; Whittington, Richard J.

2016-01-01

ABSTRACT Determining the viability of bacteria is a key outcome of in vitro cellular infection assays. Currently, this is done by culture, which is problematic for fastidious slow-growing bacteria such as Mycobacterium avium subsp. paratuberculosis, where it can take up to 4 months to confirm growth. This study aimed to identify an assay that can rapidly quantify the number of viable M. avium subsp. paratuberculosis cells in a cellular sample. Three commercially available bacterial viability assays along with a modified liquid culture method coupled with high-throughput quantitative PCR growth detection were assessed. Criteria for assessment included the ability of each assay to differentiate live and dead M. avium subsp. paratuberculosis organisms and their accuracy at low bacterial concentrations. Using the culture-based method, M. avium subsp. paratuberculosis growth was reliably detected and quantified within 2 weeks. There was a strong linear association between the 2-week growth rate and the initial inoculum concentration. The number of viable M. avium subsp. paratuberculosis cells in an unknown sample was quantified based on the growth rate, by using growth standards. In contrast, none of the commercially available viability assays were suitable for use with samples from in vitro cellular infection assays. IMPORTANCE Rapid quantification of the viability of Mycobacterium avium subsp. paratuberculosis in samples from in vitro cellular infection assays is important, as it allows these assays to be carried out on a large scale. In vitro cellular infection assays can function as a preliminary screening tool, for vaccine development or antimicrobial screening, and also to extend findings derived from experimental animal trials. Currently, by using culture, it takes up to 4 months to obtain quantifiable results regarding M. avium subsp. paratuberculosis viability after an in vitro infection assay; however, with the quantitative PCR and liquid culture method

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

PubMed Central

Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

2016-01-01

ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

A proof of concept study to assess the potential of PCR testing to detect natural Mycobacterium bovis infection in South American camelids

PubMed Central

2014-01-01

Background Cases of Mycobacterium bovis infection South American camelids have been increasing in Great Britain. Current antemortem immunological tests have some limitations. Cases at post mortem examination frequently show extensive pathology. The feasibility of detecting Mycobacterium bovis DNA in clinical samples was investigated. Findings A sensitive extraction methodology was developed and used on nasal swabs and faeces taken post-mortem to assess the potential for a PCR test to detect Mycobacterium bovis in clinical samples. The gross pathology of the studied South American camelids was scored and a significantly greater proportion of South American camelids with more severe pathology were positive in both the nasal swab and faecal PCR tests. A combination of the nasal swab and faecal PCR tests detected 63.9% of all the South American camelids with pathology that were tested. Conclusions The results suggest that antemortem diagnosis of Mycobacterium bovis in South American camelids may be possible using a PCR test on clinical samples, however more work is required to determine sensitivity and specificity, and the practicalities of applying the test in the field. PMID:24507471

A proof of concept study to assess the potential of PCR testing to detect natural Mycobacterium bovis infection in South American camelids.

PubMed

Crawshaw, Timothy R; Chanter, Jeremy I; McGoldrick, Adrian; Line, Kirsty

2014-02-07

Cases of Mycobacterium bovis infection South American camelids have been increasing in Great Britain. Current antemortem immunological tests have some limitations. Cases at post mortem examination frequently show extensive pathology. The feasibility of detecting Mycobacterium bovis DNA in clinical samples was investigated. A sensitive extraction methodology was developed and used on nasal swabs and faeces taken post-mortem to assess the potential for a PCR test to detect Mycobacterium bovis in clinical samples. The gross pathology of the studied South American camelids was scored and a significantly greater proportion of South American camelids with more severe pathology were positive in both the nasal swab and faecal PCR tests. A combination of the nasal swab and faecal PCR tests detected 63.9% of all the South American camelids with pathology that were tested. The results suggest that antemortem diagnosis of Mycobacterium bovis in South American camelids may be possible using a PCR test on clinical samples, however more work is required to determine sensitivity and specificity, and the practicalities of applying the test in the field.

Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum-Specific Atypical Memory B Cells.

PubMed

Frosch, Anne E; Odumade, Oludare A; Taylor, Justin J; Ireland, Kathleen; Ayodo, George; Ondigo, Bartholomew; Narum, David L; Vulule, John; John, Chandy C

2017-06-15

Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the Plasmodium falciparum vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels. HIV-infected individuals had a higher proportion of total atypical and total activated memory B cells (MBCs). Using an AMA1 tetramer to detect AMA1-specific B cells, HIV-infected individuals were also shown to have a higher proportion of AMA1-specific atypical MBCs. However, this proportional increase resulted in large part from a loss in the number of naive and resting MBCs rather than an increase in the number of atypical and activated cells. The loss of resting MBCs and naive B cells was mirrored in a population of cells specific for an Ag to which these individuals were unlikely to have been chronically exposed. Together, the data show that changes in P. falciparum Ag-specific B cell subsets in HIV-infected individuals mirror those in the overall B cell population, and suggest that the increased proportion of atypical MBC phenotypes found in HIV-1-infected individuals results from the loss of naive and resting MBCs. Copyright © 2017 by The American Association of Immunologists, Inc.

Outbreak of Mycobacterium chelonae infection associated with tattoo ink.

PubMed

Kennedy, Byron S; Bedard, Brenden; Younge, Mary; Tuttle, Deborah; Ammerman, Eric; Ricci, John; Doniger, Andrew S; Escuyer, Vincent E; Mitchell, Kara; Noble-Wang, Judith A; O'Connell, Heather A; Lanier, William A; Katz, Linda M; Betts, Robert F; Mercurio, Mary Gail; Scott, Glynis A; Lewis, Matthew A; Goldgeier, Mark H

2012-09-13

In January 2012, on the basis of an initial report from a dermatologist, we began to investigate an outbreak of tattoo-associated Mycobacterium chelonae skin and soft-tissue infections in Rochester, New York. The main goals were to identify the extent, cause, and form of transmission of the outbreak and to prevent further cases of infection. We analyzed data from structured interviews with the patients, histopathological testing of skin-biopsy specimens, acid-fast bacilli smears, and microbial cultures and antimicrobial susceptibility testing. We also performed DNA sequencing, pulsed-field gel electrophoresis (PFGE), cultures of the ink and ingredients used in the preparation and packaging of the ink, assessment of source water and faucets at tattoo parlors, and investigation of the ink manufacturer. Between October and December 2011, a persistent, raised, erythematous rash in the tattoo area developed in 19 persons (13 men and 6 women) within 3 weeks after they received a tattoo from a single artist who used premixed gray ink; the highest occurrence of tattooing and rash onset was in November (accounting for 15 and 12 patients, respectively). The average age of the patients was 35 years (range, 18 to 48). Skin-biopsy specimens, obtained from 17 patients, showed abnormalities in all 17, with M. chelonae isolated from 14 and confirmed by means of DNA sequencing. PFGE analysis showed indistinguishable patterns in 11 clinical isolates and one of three unopened bottles of premixed ink. Eighteen of the 19 patients were treated with appropriate antibiotics, and their condition improved. The premixed ink was the common source of infection in this outbreak. These findings led to a recall by the manufacturer.

Selection of genes of Mycobacterium tuberculosis upregulated during residence in lungs of infected mice.

PubMed

Srivastava, Vikas; Jain, Anamika; Srivastava, Brahm S; Srivastava, Ranjana

2008-05-01

In sequel to previous report [Srivastava V, Rouanet C, Srivastava R, Ramalingam B, Locht C, Srivastava BS. Macrophage-specific Mycobacterium tuberculosis genes: identification by green fluorescent protein and kanamycin resistance selection. Microbiology 2007;153:659-66], the genes of Mycobacterium tuberculosis upregulated during residence in lungs of infected mice were identified in an in vivo expression system based on kanamycin resistance. A promoter library of M. tuberculosis was constructed in a promoter trap shuttle vector pLL192 containing an artificial bicistronic operon composed of promoterless green fluorescent protein gene followed by kanamycin resistance gene. The library was introduced in M. bovis BCG and then infected in mice by intravenous route. Mice were treated twice daily with 40 mg/kg dose of kanamycin by intramuscular route for 21 days. Recombinant BCG recovered from the lungs were reinfected in mice to enrich clones surviving kanamycin treatment in the lung but sensitive to killing by kanamycin in vitro. After nucleotide sequencing of inserts from these clones, 20 genes belonging to fatty acids metabolism, membrane transport, nitric oxide defence and PE_PGRS/PPE family were identified. Real-time PCR analysis using RNA isolated from M. tuberculosis grown in vitro and from the lungs, confirmed upregulation of genes from 2 to 20-fold in vivo compared to growth in vitro. Several of these select 20 genes were also found upregulated ex vivo in macrophage-like cell line J774A.1, thus, suggesting a correlation in mycobacterial gene expression between ex vivo and in vivo conditions.

Source investigation of two outbreaks of skin and soft tissue infection by Mycobacterium abscessus subsp. abscessus in Venezuela.

PubMed

Torres-Coy, J A; Rodríguez-Castillo, B A; Pérez-Alfonzo, R; DE Waard, J H

2016-04-01

Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela.

The atypical pneumonias: clinical diagnosis and importance.

PubMed

Cunha, B A

2006-05-01

The most common atypical pneumonias are caused by three zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and three nonzoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical CAPs by the pattern of extrapulmonary organ involvement which is characteristic for each atypical CAP. Zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history. The commonest clinical problem is to differentiate legionnaire's disease from typical CAP as well as from C. pneumoniae or M. pneumonia infection. Legionella is the most important atypical pathogen in terms of severity. It may be clinically differentiated from typical CAP and other atypical pathogens by the use of a weighted point system of syndromic diagnosis based on the characteristic pattern of extrapulmonary features. Because legionnaire's disease often presents as severe CAP, a presumptive diagnosis of Legionella should prompt specific testing and empirical anti-Legionella therapy such as the Winthrop-University Hospital Infectious Disease Division's weighted point score system. Most atypical pathogens are difficult or dangerous to isolate and a definitive laboratory diagnosis is usually based on indirect, i.e., direct flourescent antibody (DFA), indirect flourescent antibody (IFA). Atypical CAP is virtually always monomicrobial; increased IFA IgG tests indicate past exposure and not concurrent infection. Anti-Legionella antibiotics include macrolides, doxycycline, rifampin, quinolones, and telithromycin. The drugs with the highest level of anti-Legionella activity are quinolones and telithromycin. Therapy is usually continued for 2 weeks if potent anti-Legionella drugs are

Genotype heterogeneity of Mycobacterium tuberculosis within geospatial hotspots suggests foci of imported infection in Sydney, Australia.

PubMed

Gurjav, Ulziijargal; Jelfs, Peter; Hill-Cawthorne, Grant A; Marais, Ben J; Sintchenko, Vitali

2016-06-01

In recent years the State of New South Wales (NSW), Australia, has maintained a low tuberculosis incidence rate with little evidence of local transmission. Nearly 90% of notified tuberculosis cases occurred in people born in tuberculosis-endemic countries. We analyzed geographic, epidemiological and genotypic data of all culture-confirmed tuberculosis cases to identify the bacterial and demographic determinants of tuberculosis hotspot areas in NSW. Standard 24-loci mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-24) typing was performed on all isolates recovered between 2009 and 2013. In total 1692/1841 (91.9%) cases with confirmed Mycobacterium tuberculosis infection had complete MIRU-24 and demographic data and were included in the study. Despite some year-to-year variability, spatio-temporal analysis identified four tuberculosis hotspots. The incidence rate and the relative risk of tuberculosis in these hotspots were 2- to 10-fold and 4- to 8-fold higher than the state average, respectively. MIRU-24 profiles of M. tuberculosis isolates associated with these hotspots revealed high levels of heterogeneity. This suggests that these spatio-temporal hotspots, within this low incidence setting, can represent areas of predominantly imported infection rather than clusters of cases due to local transmission. These findings provide important epidemiological insight and demonstrate the value of combining tuberculosis genotyping and spatiotemporal data to guide better-targeted public health interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

Atypical Rocky Mountain spotted fever with polyarticular arthritis.

PubMed

Chaudhry, Muhammad A; Scofield, Robert Hal

2013-11-01

Rocky Mountain spotted fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently, RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare. The purpose of this study is to describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands and to review the previously reported patients with rickettsial infection and inflammatory arthritis. An 18-year-old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on examination in addition to an erythematosus macular rash and occasional fever. Acute and convalescent serology demonstrated R rickettsi infection. She was successfully treated with doxycycline. Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with 8 previously reported patients, only 1 of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations.

Atypical Rocky Mountain spotted fever with polyarticular arthritis

PubMed Central

Chaudhry, Muhammad A.; Hal Scofield, R.

2017-01-01

Background Rocky Mountain Spotted Fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare Purpose Describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands, and to review the previously reported patients with rickettsial infection and inflammatory arthritis Patient An 18 year old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on exam as well as an erythematosus macular rash, and occasional fever. Acute and convalescent serology demonstrated Rickettsia rickettsi infection. She was successfully treated with doxycycline. Conclusion Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with eight previously reported patients, only one of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations. PMID:24157965

Draft Genome Sequence of Mycobacterium chimaera Type ...

EPA Pesticide Factsheets

We report the draft genome sequence of the type strain Mycobacterium chimaera Fl-0169T, a member of the Mycobacterium avium complex (MAC). M. chimaera Fl-0169T was isolated from a patient in Italy and is highly similar to strains of M. chimaera isolated in Ireland, though Fl-0169T possesses unique virulence genes. Evidence suggests that M. avium, M. intracellulare, and M. chimaera are differently virulent and a comparative genomic analysis is critically needed to identify diagnostic targets that reliably differentiate species of MAC. With treatment costs for Mycobacterium infections estimated to be >$1.8 B annually in the U.S., correct species identification will result in improved treatment selection, lower costs, and improved patient outcomes.

Mycobacteriosis in a black-tailed deer (Odocoileus hemionus columbianus) caused by Mycobacterium kansasii

USGS Publications Warehouse

Hall, P.B.; Bender, L.C.; Garner, M.M.

2005-01-01

An eviscerated hunter-harvested female black-tailed deer (Odocoileus hemionus columbianus) was submitted to the Washington Department of Fish and Wildlife. The deer was emaciated, devoid of adipose tissue, and the parietal surface of the thoracic cavity contained multiple granulomas. Acid-fast bacteria were detected histologically from the granulomas and were isolated and identified as Mycobacterium kansasii, a nontuberculous mycobacterium sporadically reported to cause tuberculosis-like disease in a variety of vertebrates. This was the first report of symptomatic disease caused by M. kansasii in free-ranging deer. This case indicates that atypical mycobacteria can cause tuberculosis-like disease in free-ranging deer and illustrates the importance of identifying causative agents of tuberculosis-like disease in wildlife. Copyright 2005 by American Association of Zoo Veterinarians.

Pulmonary infection caused by Mycobacterium kansasii: findings on computed tomography of the chest*

PubMed Central

Mogami, Roberto; Goldenberg, Telma; de Marca, Patricia Gomes Cytrangulo; Mello, Fernanda Carvalho de Queiroz; Lopes, Agnaldo José

2016-01-01

Objective To describe the main tomography findings in patients diagnosed with pulmonary infection caused by Mycobacterium kansasii. Materials and Methods Retrospective study of computed tomography scans of 19 patients with pulmonary infection by M. kansasii. Results Of the 19 patients evaluated, 10 (52.6%) were male and 9 (47.4%) were female. The mean age of the patients was 58 years (range, 33-76 years). Computed tomography findings were as follows: architectural distortion, in 17 patients (89.5%); reticular opacities and bronchiectasis, in 16 (84.2%); cavities, in 14 (73.7%); centrilobular nodules, in 13 (68.4%); small consolidations, in 10 (52.6%); atelectasis and large consolidations, in 9 (47.4%); subpleural blebs and emphysema, in 6 (31.6%); and adenopathy, in 1 (5.3%). Conclusion There was a predominance of cavities, as well as of involvement of the small and large airways. The airway disease was characterized by bronchiectasis and bronchiolitis presenting as centrilobular nodules. PMID:27777472

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.

PubMed

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M; Casadevall, Arturo; Flynn, JoAnne

2014-12-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection

PubMed Central

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M.; Casadevall, Arturo; Flynn, JoAnne

2014-01-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. PMID:25458990

Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection.

PubMed

Treerat, P; Prince, O; Cruz-Lagunas, A; Muñoz-Torrico, M; Salazar-Lezama, M A; Selman, M; Fallert-Junecko, B; Reinhardt, T A; Alcorn, J F; Kaushal, D; Zuñiga, J; Rangel-Moreno, J; Kolls, J K; Khader, S A

2017-07-01

Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces. Thus far, collective data show that IL-22 deficient mice are not more susceptible to aerosolized infection with less virulent Mtb strains. Thus, in this study we addressed the functional role for the IL-22 pathway in immunity to emerging Mtb isolates, using W-Beijing lineage member, Mtb HN878 as a prototype. We show that Mtb HN878 stimulates IL-22 production in TLR2 dependent manner and IL-22 mediates protective immunity during chronic stages of Mtb HN878 infection in mice. Interestingly, IL-22-dependent pathways in both epithelial cells and macrophages mediate protective mechanisms for Mtb HN878 control. Thus, our results project a new protective role for IL-22 in emerging Mtb infections.

Recurrent catheter-related infection caused by a single clone of Mycobacterium chelonae with two colonial morphotypes.

PubMed

Hsueh, P R; Teng, L J; Yang, P C; Chen, Y C; Ho, S W; Luh, K T

1998-05-01

We describe herein a recurrent catheter-related (Port-A-Cath; Smiths Industries Medical Systems [SIMS] Deltec, Inc., St. Paul, Minn.) infection caused by multidrug-resistant Mycobacterium chelonae with two colonial morphotypes in a 53-year-old woman with gastric adenocarcinoma. Four isolates recovered from this patient within a 3-month period were found to belong to a single clone on the basis of the isolates' identical antibiotypes as determined by the E test and their identical random amplified polymorphic DNA patterns.

Detection and partial molecular characterization of atypical plum pox virus isolates from naturally infected sour cherry.

PubMed

Chirkov, Sergei; Ivanov, Peter; Sheveleva, Anna

2013-06-01

Atypical isolates of plum pox virus (PPV) were discovered in naturally infected sour cherry in urban ornamental plantings in Moscow, Russia. The isolates were detected by polyclonal double antibody sandwich ELISA and RT-PCR using universal primers specific for the 3'-non-coding and coat protein (CP) regions of the genome but failed to be recognized by triple antibody sandwich ELISA with the universal monoclonal antibody 5B and by RT-PCR using primers specific to for PPV strains D, M, C and W. Sequence analysis of the CP genes of nine isolates revealed 99.2-100 % within-group identity and 62-85 % identity to conventional PPV strains. Phylogenetic analysis showed that the atypical isolates represent a group that is distinct from the known PPV strains. Alignment of the N-terminal amino acid sequences of CP demonstrated their close similarity to those of a new tentative PPV strain, CR.

PATTERNS OF MYCOBACTERIUM LEPRAE INFECTION IN WILD NINE-BANDED ARMADILLOS (DASYPUS NOVEMCINCTUS) IN MISSISSIPPI, USA.

PubMed

Perez-Heydrich, Carolina; Loughry, W J; Anderson, Corey Devin; Oli, Madan K

2016-07-01

The nine-banded armadillo ( Dasypus novemcinctus ) is the only known nonhuman reservoir of Mycobacterium leprae , the causative agent of Hansen's disease or leprosy. We conducted a 6-yr study on a wild population of armadillos in western Mississippi that was exposed to M. leprae to evaluate the importance of demographic and spatial risk factors on individual antibody status. We found that spatially derived covariates were not predictive of antibody status. Furthermore, analyses revealed no evidence of clustering by antibody-positive individuals. Lactating females and adult males had higher odds of being antibody positive than did nonlactating females. No juveniles or yearlings were antibody positive. Results of these analyses support the hypothesis that M. leprae infection patterns are spatially homogeneous within this armadillo population. Further research related to movement patterns, contact among individuals, antibody status, and environmental factors could help address hypotheses related to the role of environmental transmission on M. leprae infection and the mechanisms underlying the differential infection patterns among demographic groups.

Seroprevalence and risk factors of Mycobacterium avium subspecies paratuberculosis infection in domestic sika deer in China.

PubMed

Meng, Qing-Feng; Li, Ying; Yang, Fan; Yao, Gui-Zhi; Qian, Ai-Dong; Wang, Wei-Li; Cong, Wei

2015-06-01

Paratuberculosis or Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic infectious granulomatous enteritis of ruminants and other animals, which has a worldwide occurrence, but little is known of MAP infection in domestic sika deer in Jilin Province, China. The objective of the present investigation was to examine seroprevalence and risk factors of MAP infection in Jilin Province. Serum samples collected from 1400 sika deer from 16 sika deer herds were collected in the 4 districts of the province between May 2013 and August 2014 and were tested independently for the presence of antibodies against MAP. A total of 247 (17.64 %) sika deer tested positive for MAP antibodies using a commercially available enzyme immunoassay kit. The management level of farm and collecting region of sika deer was the main risk factor associated with MAP infection. The present study revealed the seroprevalence of MAP infection in sika deer in Jilin Province, China, which provided the baseline data for taking comprehensive countermeasures and measures in effectively preventing and controlling MAP infection in sika deer.

Intranasal IFNγ extends passive IgA antibody protection of mice against Mycobacterium tuberculosis lung infection

PubMed Central

Reljic, R; Clark, S O; Williams, A; Falero-Diaz, G; Singh, M; Challacombe, S; Marsh, P D; Ivanyi, J

2006-01-01

Intranasal inoculation of mice with monoclonal IgA against the α-crystallin (acr1) antigen can diminish the tuberculous infection in the lungs. As this effect has been observed only over a short-term, we investigated if it could be extended by inoculation of IFNγ 3 days before infection, and further coinoculations with IgA, at 2 h before and 2 and 7 days after aerosol infection with Mycobacterium tuberculosis H37Rv. This treatment reduced the lung infection at 4 weeks more than either IgA or IFNγ alone (i.e. 17-fold, from 4·2 × 107 to 2·5 × 106 CFU, P = 0·006), accompanied also by lower granulomatous infiltration of the lungs. IFNγ added prior to infection of mouse peritoneal macrophages with IgA-opsonized bacilli resulted in a synergistic increase of nitric oxide and TNFα production and a 2–3 fold decrease in bacterial counts. Our improved results suggest, that combined treatment with IFNγ and IgA could be developed towards prophylactic treatment of AIDS patients, or as an adjunct to chemotherapy. PMID:16487246

Autophagy protects type II alveolar epithelial cells from Mycobacterium tuberculosis infection

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

Guo, Xu-Guang; Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou; Ji, Tian-Xing

Highlights: ► We investigated the protective effect of autophagy pathway against MTB infection. ► MTB-infected A549 cells had higher LDH release. ► Inhibition of autophagy signaling significantly enhanced the MTB-induced necrosis. ► Autophagy prevents apoptosis and promotes cell survival in infected cells. -- Abstract: This study was designed to investigate the protective effect of the autophagy signaling pathway against Mycobacterium tuberculosis infection in type II alveolar epithelial cells. An in vitro M. tuberculosis system was established using human A549 cells. Infection-induced changes in the expression of the autophagic marker LC3 were assessed by reverse transcription-PCR and Western blotting. Morphological changesmore » in autophagosomes were detected by transmission electron microscopy (TEM). The function of the autophagy signaling pathway during infection was assessed by measuring the level of cell death and the amount of lactate dehydrogenase (LDH) released in the presence or absence of the inhibitor 3-methyladenine (3-MA). In addition, effects on LDH release were assessed after the siRNA-mediated knockdown of the essential autophagosomal structural membrane protein Atg5. LC3 mRNA expression was significantly reduced in M.tuberculosis-infected A549 cells (16888.76 ± 1576.34 vs. uninfected: 12744.29 ± 1089.37; P < 0.05). TEM revealed M.tuberculosis bacilli-containing compartments that were surrounded by double membranes characteristic of the autophagic process. M.tuberculosis-infected A549 cells released more LDH (1.45 ± 0.12 vs. uninfected: 0.45 ± 0.04; P < 0.05). The inhibition of autophagy signaling significantly enhanced M.tuberculosis-induced necrosis (3-MA: 75 ± 5% vs. untreated: 15 ± 1%; P < 0.05) and LDH release (3-MA: 2.50 ± 0.24 vs. untreated: 0.45 ± 0.04; Atg5 knockdown: 3.19 ± 0.29 vs. untreated: 1.28 ± 0.11; P < 0.05). Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar

Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy

PubMed Central

Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano

2016-01-01

Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions. PMID

Mycobacterium species related to M. leprae and M. lepromatosis from cows with bovine nodular thelitis.

PubMed

Pin, Didier; Guérin-Faublée, Véronique; Garreau, Virginie; Breysse, Franck; Dumitrescu, Oana; Flandrois, Jean-Pierre; Lina, Gerard

2014-12-01

Bovine nodular thelitis is a granulomatous dermatitis associated with infection with acid-fast bacteria. To identify the mycobacterium responsible for this infection, we conducted phylogenetic investigations based on partial sequencing of 6 genes. These bacteria were identified as an undescribed Mycobacterium species that was phylogenetically related to M. leprae and M. lepromatosis.

Multifaceted role of lipids in Mycobacterium leprae.

PubMed

Kaur, Gurkamaljit; Kaur, Jagdeep

2017-03-01

Mycobacterium leprae must adopt a metabolic strategy and undergo various metabolic alterations upon infection to survive inside the human body for years in a dormant state. A change in lipid homeostasis upon infection is highly pronounced in Mycobacterium leprae. Lipids play an essential role in the survival and pathogenesis of mycobacteria. Lipids are present in several forms and serve multiple roles from being a source of nutrition, providing rigidity, evading the host immune response to serving as virulence factors, etc. The synthesis and degradation of lipids is a highly regulated process and is the key to future drug designing and diagnosis for mycobacteria. In the current review, an account of the distinct roles served by lipids, the mechanism of their synthesis and degradation has been elucidated.

Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

PubMed Central

López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C.; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

2016-01-01

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

Immunohistochemical characterization of tuberculous lesions in sheep naturally infected with Mycobacterium bovis.

PubMed

Vallejo, Raquel; García Marín, Juan Francisco; Juste, Ramón Antonio; Muñoz-Mendoza, Marta; Salguero, Francisco Javier; Balseiro, Ana

2018-05-04

Sheep have been traditionally considered as less susceptible to Mycobacterium bovis (Mbovis) infection than other domestic ruminants such as cattle and goats. However, there is increasing evidence for the role of this species as a domestic Mbovis reservoir, mostly when sheep share grazing fields with infected cattle and goats. Nevertheless, there is a lack of information about the pathogenesis and the immune response of Mbovis infection in sheep. The goals of this study were to characterize the granuloma stages produced by the natural infection of Mbovis in sheep, to compare them with other species and to identify possible differences in the sheep immune response. Samples from bronchial lymph nodes from twelve Mbovis-naturally infected sheep were used. Four immunohistochemical protocols for the specific detection of T-lymphocytes, B-lymphocytes, plasma cells and macrophages were performed to study the local immune reaction within the granulomas. Differences were observed in the predominant cell type present in each type of granuloma, as well as differences and similarities with the development of tuberculous granulomas in other species. Very low numbers of T-lymphocytes were observed in all granuloma types indicating that specific cellular immune response mediated by T-cells might not be of much importance in sheep in the early stages of infection, when macrophages are the predominant cell type within lesions. Plasma cells and mainly B lymphocytes increased considerably as the granuloma developed being attracted to the lesions in a shift towards a Th2 response against the increasing amounts of mycobacteria. Therefore, we have proposed that the granulomas could be defined as initial, developed and terminal. Results showed that the study of the lymphoid tissue granulomata reinforces the view that the three different types of granuloma represent stages of lesion progression and suggest an explanation to the higher resistance of sheep based on a higher effective innate

Comparative genomics of archived pyrazinamide resistant Mycobacterium tuberculosis complex isolates from Uganda

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis is a ‘neglected zoonosis’ and its contribution to the proportion of Mycobacterium tuberculosis complex infections in humans is unknown. A retrospective study on archived Mycobacterium tuberculosis complex (MTC) isolates from a reference laboratory in Uganda was undertaken to iden...

Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals.

PubMed

Ly, Judy; Lagman, Minette; Saing, Tommy; Singh, Manpreet Kaur; Tudela, Enrique Vera; Morris, Devin; Anderson, Jessica; Daliva, John; Ochoa, Cesar; Patel, Nishita; Pearce, Daniel; Venketaraman, Vishwanath

2015-11-01

Cytokines are signaling biomolecules that serve as key regulators of our immune system. CD4(+) T-cells can be grouped into 2 major categories based on their cytokine profile: T-helper 1 (TH1) subset and T-helper 2 (TH2) subset. Protective immunity against HIV infection requires TH1-directed CD4 T-cell responses, mediated by cytokines, such as interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Cytokines released by the TH1 subset of CD4 T-cells are considered important for mediating effective immune responses against intracellular pathogens such as Mycobacterium tuberculosis (M. tb). Oxidative stress and redox imbalance that occur during HIV infection often lead to inappropriate immune responses. Glutathione (GSH) is an antioxidant present in nearly all cells and is recognized for its function in maintaining redox homeostasis. Our laboratory previously reported that individuals with HIV infection have lower levels of GSH. In this study, we report a link between lower levels of GSH and dysregulation of TH1- and TH2-associated cytokines in the plasma samples of HIV-positive subjects. Furthermore, we demonstrate that supplementing individuals with HIV infection for 13 weeks with liposomal GSH (lGSH) resulted in a significant increase in the levels of TH1 cytokines, IL-1β, IL-12, IFN-γ, and TNF-α. lGSH supplementation in individuals with HIV infection also resulted in a substantial decrease in the levels of free radicals and immunosuppressive cytokines, IL-10 and TGF-β, relative to those in a placebo-controlled cohort. Finally, we determined the effects of lGSH supplementation in improving the functions of immune cells to control M. tb infection by conducting in vitro assays using peripheral blood mononuclear cells collected from HIV-positive individuals at post-GSH supplementation. Our studies establish a correlation between low levels of GSH and increased susceptibility to M. tb infection through TH2-directed response

Age- and Sex-Specific Social Contact Patterns and Incidence of Mycobacterium tuberculosis Infection.

PubMed

Dodd, Peter J; Looker, Clare; Plumb, Ian D; Bond, Virginia; Schaap, Ab; Shanaube, Kwame; Muyoyeta, Monde; Vynnycky, Emilia; Godfrey-Faussett, Peter; Corbett, Elizabeth L; Beyers, Nulda; Ayles, Helen; White, Richard G

2016-01-15

We aimed to model the incidence of infection with Mycobacterium tuberculosis among adults using data on infection incidence in children, disease prevalence in adults, and social contact patterns. We conducted a cross-sectional face-to-face survey of adults in 2011, enumerating "close" (shared conversation) and "casual" (shared indoor space) social contacts in 16 Zambian communities and 8 South African communities. We modeled the incidence of M. tuberculosis infection in all age groups using these contact patterns, as well as the observed incidence of M. tuberculosis infection in children and the prevalence of tuberculosis disease in adults. A total of 3,528 adults participated in the study. The reported rates of close and casual contact were 4.9 per adult per day (95% confidence interval: 4.6, 5.2) and 10.4 per adult per day (95% confidence interval: 9.3, 11.6), respectively. Rates of close contact were higher for adults in larger households and rural areas. There was preferential mixing of close contacts within age groups and within sexes. The estimated incidence of M. tuberculosis infection in adults was 1.5-6 times higher (2.5%-10% per year) than that in children. More than 50% of infections in men, women, and children were estimated to be due to contact with adult men. We conclude that estimates of infection incidence based on surveys in children might underestimate incidence in adults. Most infections may be due to contact with adult men. Treatment and control of tuberculosis in men is critical to protecting men, women, and children from tuberculosis. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques.

PubMed

Phuah, Jiayao; Wong, Eileen A; Gideon, Hannah P; Maiello, Pauline; Coleman, M Teresa; Hendricks, Matthew R; Ruden, Rachel; Cirrincione, Lauren R; Chan, John; Lin, Philana Ling; Flynn, JoAnne L

2016-05-01

Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.

PubMed

Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

2016-02-01

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Induction therapy with linezolid/clarithromycin combination for Mycobacterium chelonae skin infections in immunocompromised hosts.

PubMed

Parize, P; Hamelin, A; Veziris, N; Morand, P C; Guillemain, R; Lortholary, O; Dupin, N

2016-01-01

The optimal management of Mycobacterium chelonae disease in immunocompromised patients remains unclear. A combination of antimicrobial agents is recommended as monotherapy with clarithromycin has been associated with clinical failures due to acquired resistance. We aim to report the efficacy and tolerability of linezolid in association with clarithromycin for the treatment of M. chelonae infections in immunocompromised patients. We describe four immunocompromised patients treated by linezolid and clarithromycin for cutaneous M. chelonae disease. This combination was associated with rapid clinical efficacy in all patients with no relapse observed after a median follow-up of 2.25 years (1.4 years). However, this treatment was responsible for frequent adverse events including thrombocytopaenia, myalgia and mitochondrial toxicity. All adverse effects were reversible after linezolid discontinuation. We therefore suggest linezolid/clarithromycin combination as the initial therapeutic strategy for M. chelonae skin infections in immunocompromised patients. © 2015 European Academy of Dermatology and Venereology.

DETECTION,QUANTIFICATION AND CHARACTERIZATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS IN DRINKING WATER.

EPA Science Inventory

Bacteria belonging to the Mycobacterium avium complex (MAC), including Mycobacterium avium and M. intracellulare, are clinically relevant and cause a myriad of opportunistic infections. Children, the elderly, and persons with previous lung conditions or immune system dysfunction...

An atypical pattern of Epstein-Barr virus infection in a case with idiopathic tubulointerstitial nephritis.

PubMed

Okada, Hirokazu; Ikeda, Naofumi; Kobayashi, Tatsuya; Inoue, Tsutomu; Kanno, Yoshihiko; Sugahara, Souichi; Nakamoto, Hidetomo; Yamamoto, Takako; Suzuki, Hiromichi

2002-10-01

Recently, Epstein-Barr virus (EBV) received attention because a latent form of its infection in renal proximal tubular epithelial cells was found to cause idiopathic, chronic tubulointerstitial nephritis. In this report, we describe the case of a patient with a replicative form of EBV infection, chronic active EBV infection (CAEBV), who developed acute tubulointerstitial nephritis and minimal change nephrotic syndrome. A renal biopsy revealed papillary infoldings of atypical tubular epithelium and adjacent dense infiltration of lymphocytes. Using in situ polymerase chain reaction methods, we detected the EBV genome in some of the infiltrating lymphocytes, but not in the tubular epithelial cells. EBV-infected T cells are thought to activate other educated T cells, as well as secrete an unrestricted variety of cytokines, thus playing a pivotal role in CAEBV and its end organ disease. Therefore, in our case, the CAEBV activated, educated T cells may have followed the EBV-infected lymphocytes as they infiltrated into the peritubular interstitium, and promoted focal tubular epithelial atypia and minimal change nephrotic syndrome. The long-term observation of such patients is important because CAEBV may progress into lymphoproliferative diseases. Copyright 2002 S. Karger AG, Basel

Mycobacterium Species Related to M. leprae and M. lepromatosis from Cows with Bovine Nodular Thelitis

PubMed Central

Guérin-Faublée, Véronique; Garreau, Virginie; Breysse, Franck; Dumitrescu, Oana; Flandrois, Jean-Pierre; Lina, Gerard

2014-01-01

Bovine nodular thelitis is a granulomatous dermatitis associated with infection with acid-fast bacteria. To identify the mycobacterium responsible for this infection, we conducted phylogenetic investigations based on partial sequencing of 6 genes. These bacteria were identified as an undescribed Mycobacterium species that was phylogenetically related to M. leprae and M. lepromatosis. PMID:25417797

Anomalies in T Cell Function Are Associated With Individuals at Risk of Mycobacterium abscessus Complex Infection

PubMed Central

Lutzky, Viviana P.; Ratnatunga, Champa N.; Smith, Daniel J.; Kupz, Andreas; Doolan, Denise L.; Reid, David W.; Thomson, Rachel M.; Bell, Scott C.; Miles, John J.

2018-01-01

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFα production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts. PMID:29942313

Anomalies in T Cell Function Are Associated With Individuals at Risk of Mycobacterium abscessus Complex Infection.

PubMed

Lutzky, Viviana P; Ratnatunga, Champa N; Smith, Daniel J; Kupz, Andreas; Doolan, Denise L; Reid, David W; Thomson, Rachel M; Bell, Scott C; Miles, John J

2018-01-01

The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFα production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts.

Mycobacterium chimaera infections in post–operative patients exposed to heater–cooler devices: An overview

PubMed Central

Ogunremi, T; Taylor, G; Johnston, L; Amaratunga, K; Muller, M; Coady, A; Defalco, K; Dunn, K; Johnstone, J; Smith, S; Embree, J; Henry, B; Stafford, J

2017-01-01

A multi-country outbreak of Mycobacterium chimaera infection associated with contaminated heater–cooler devices (HCDs) has been reported, with more than 70 cases in Europe and the United States and two cases in Canada to date. The epidemiological and microbiological characteristics of this outbreak provide evidence for common-source transmission of M. chimaera from the exhaust air of intrinsically contaminated HCDs to patients during cardiac surgery. To date, all reported cases have been associated with Stöckert 3T HCDs manufactured at one plant by LivaNova prior to September 2014. Implantation of prosthetic material increases the risk of infection. Infections usually present as prosthetic valve endocarditis, vascular graft infection or disseminated infection. Reported mortality rates have varied, but were often over 40%. Several measures are recommended to facilitate case-finding and mitigate risk of exposure. The feasibility of some risk mitigation measures and their effectiveness in reducing the risk of exposure are yet to be determined. Until HCDs are redesigned in a manner that prevents water contamination and aerosolization, separating the HCD exhaust air from the operating room air during surgery may be the most effective risk mitigation strategy. However, possible unintended consequences of this approach should be considered. This overview summarizes findings from peer-reviewed and other relevant national documents on key features of the outbreak, including the source, identified risk factors for infection, signs and symptoms of infection, burden of disease, risk mitigation measures, management challenges and knowledge gaps.

Mycobacterium chimaera infections in post-operative patients exposed to heater-cooler devices: An overview.

PubMed

Ogunremi, T; Taylor, G; Johnston, L; Amaratunga, K; Muller, M; Coady, A; Defalco, K; Dunn, K; Johnstone, J; Smith, S; Embree, J; Henry, B; Stafford, J

2017-05-04

A multi-country outbreak of Mycobacterium chimaera infection associated with contaminated heater-cooler devices (HCDs) has been reported, with more than 70 cases in Europe and the United States and two cases in Canada to date. The epidemiological and microbiological characteristics of this outbreak provide evidence for common-source transmission of M. chimaera from the exhaust air of intrinsically contaminated HCDs to patients during cardiac surgery. To date, all reported cases have been associated with Stöckert 3T HCDs manufactured at one plant by LivaNova prior to September 2014. Implantation of prosthetic material increases the risk of infection. Infections usually present as prosthetic valve endocarditis, vascular graft infection or disseminated infection. Reported mortality rates have varied, but were often over 40%. Several measures are recommended to facilitate case-finding and mitigate risk of exposure. The feasibility of some risk mitigation measures and their effectiveness in reducing the risk of exposure are yet to be determined. Until HCDs are redesigned in a manner that prevents water contamination and aerosolization, separating the HCD exhaust air from the operating room air during surgery may be the most effective risk mitigation strategy. However, possible unintended consequences of this approach should be considered. This overview summarizes findings from peer-reviewed and other relevant national documents on key features of the outbreak, including the source, identified risk factors for infection, signs and symptoms of infection, burden of disease, risk mitigation measures, management challenges and knowledge gaps.

Nasal PCR assay for the detection of Mycobacterium leprae pra gene to study subclinical infection in a community.

PubMed

Arunagiri, Kamalanathan; Sangeetha, Gopalakrishnan; Sugashini, Padmavathy Krishnan; Balaraman, Sekar; Showkath Ali, M K

2017-03-01

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Identification of Mycobacterium leprae is difficult in part due to the inability of the leprosy bacillus to grow in vitro. A number of diagnostic methods for leprosy diagnosis have been proposed. Both serological tests and molecular probes have shown certain potential for detection and identification of Mycobacterium leprae in patients. In this study, we have investigated whether Mycobacterium leprae DNA from the nasal secretion of healthy household contacts and the non contacts could be detected through PCR amplification as a method to study the sub clinical infection in a community. A total of 200 samples, 100 each from contacts and non contacts representing all age groups and sex were included in this study. The M. leprae specific primer (proline-rich region) of pra gene was selected and PCR was performed using extracted DNA from the sample. A total of 13 samples were found to be positive for nasal PCR for pra gene among the male and female contacts out of which 7% were males and 6% were females. Even though several diagnostic tools are available to detect the cases of leprosy, they lack the specificity and sensitivity. PCR technology has demonstrated the improved diagnostic accuracy for epidemiological studies and requires minimal time. Although nasal PCR studies have been reported from many countries it is not usually recommended due to the high percentage of negative results in the contact. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity of Mycobacterium bovis to common beef processing interventions

USDA-ARS?s Scientific Manuscript database

Introduction. Cattle infected with Mycobacterium bovis, the causative agent of bovine tuberculosis and a relevant zoonosis to humans, may be sent to slaughter before diagnosis of infection because of slow multiplication of the pathogen. Purpose. This study evaluates multiple processing interventi...

Atypical Presentation of Herpes Simplex Virus Type 2 Infection Refractory to Treatment With Acyclovir in 2 Hematologic Patients.

PubMed

Nieto Rodríguez, D; Sendagorta Cudós, E; Rueda Carnero, J M; Herranz Pinto, P

2017-12-01

Herpesvirus infections are not uncommon in hematologic patients. Our first patient, diagnosed with chronic lymphatic leukemia, presented extensive genital herpes infection refractory to treatment with acyclovir and with a partial response to foscarnet, which had to be withdrawn due to systemic adverse effects. The second patient, diagnosed with follicular Hodgkin lymphoma, presented hypertrophic herpes infection refractory to treatment with acyclovir but that responded to intralesional cidofovir and topical imiquimod. As in other immunodepressed patients, herpesvirus infection in hematologic patients can present atypical manifestations, as well as resistance to treatments that act via the viral thymidine kinase. A high level of clinical suspicion is therefore needed to make an early diagnosis, together with extensive knowledge of the different treatments available. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Phylogenomic analysis of the species of the Mycobacterium tuberculosis complex demonstrates that Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii are later heterotypic synonyms of Mycobacterium tuberculosis.

PubMed

Riojas, Marco A; McGough, Katya J; Rider-Riojas, Cristin J; Rastogi, Nalin; Hazbón, Manzour Hernando

2018-01-01

The species within the Mycobacterium tuberculosis Complex (MTBC) have undergone numerous taxonomic and nomenclatural changes, leaving the true structure of the MTBC in doubt. We used next-generation sequencing (NGS), digital DNA-DNA hybridization (dDDH), and average nucleotide identity (ANI) to investigate the relationship between these species. The type strains of Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii were sequenced via NGS. Pairwise dDDH and ANI comparisons between these, previously sequenced MTBC type strain genomes (including 'Mycobacterium canettii', 'Mycobacterium mungi' and 'Mycobacterium orygis') and M. tuberculosis H37Rv T were performed. Further, all available genome sequences in GenBank for species in or putatively in the MTBC were compared to H37Rv T . Pairwise results indicated that all of the type strains of the species are extremely closely related to each other (dDDH: 91.2-99.2 %, ANI: 99.21-99.92 %), greatly exceeding the respective species delineation thresholds, thus indicating that they belong to the same species. Results from the GenBank genomes indicate that all the strains examined are within the circumscription of H37Rv T (dDDH: 83.5-100 %). We, therefore, formally propose a union of the species of the MTBC as M. tuberculosis. M. africanum, M. bovis, M. caprae, M. microti and M. pinnipedii are reclassified as later heterotypic synonyms of M. tuberculosis. 'M. canettii', 'M. mungi', and 'M. orygis' are classified as strains of the species M. tuberculosis. We further recommend use of the infrasubspecific term 'variant' ('var.') and infrasubspecific designations that generally retain the historical nomenclature associated with the groups or otherwise convey such characteristics, e.g. M. tuberculosis var. bovis.

Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

PubMed Central

Portugal, Silvia; Tipton, Christopher M; Sohn, Haewon; Kone, Younoussou; Wang, Jing; Li, Shanping; Skinner, Jeff; Virtaneva, Kimmo; Sturdevant, Daniel E; Porcella, Stephen F; Doumbo, Ogobara K; Doumbo, Safiatou; Kayentao, Kassoum; Ongoiba, Aissata; Traore, Boubacar; Sanz, Inaki; Pierce, Susan K; Crompton, Peter D

2015-01-01

Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity. DOI: http://dx.doi.org/10.7554/eLife.07218.001 PMID:25955968

Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

PubMed Central

Hoang, Truc; Agger, Else Marie; Cassidy, Joseph P.; Christensen, Jan P.

2015-01-01

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse of Mycobacterium tuberculosis, as well as increased pathology, in both Mycobacterium bovis BCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ+ TNF-α+ and IFN-γ+ cells). PEM during M. tuberculosis infection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine against M. tuberculosis infection. PMID:25754202

Lipolytic enzymes in Mycobacterium tuberculosis.

PubMed

Côtes, K; Bakala N'goma, J C; Dhouib, R; Douchet, I; Maurin, D; Carrière, F; Canaan, S

2008-04-01

Mycobacterium tuberculosis is a bacterial pathogen that can persist for decades in an infected patient without causing a disease. In vivo, the tubercle bacillus present in the lungs store triacylglycerols in inclusion bodies. The same process can be observed in vitro when the bacteria infect adipose tissues. Indeed, before entering in the dormant state, bacteria accumulate lipids originating from the host cell membrane degradation and from de novo synthesis. During the reactivation phase, these lipids are hydrolysed and the infection process occurs. The degradation of both extra and intracellular lipids can be directly related to the presence of lipolytic enzymes in mycobacteria, which have been ignored during a long period particularly due to the difficulties to obtain a high expression level of these enzymes in M. tuberculosis. The completion of the M. tuberculosis genome offered new opportunity to this kind of study. The aim of this review is to focus on the recent results obtained in the field of mycobacterium lipolytic enzymes and although no experimental proof has been shown in vivo, it is tempting to speculate that these enzymes could be involved in the virulence and pathogenicity processes.

Utility of a fecal real-time PCR protocol for detection of Mycobacterium bovis infection in African buffalo (Syncerus caffer).

PubMed

Roug, Annette; Geoghegan, Claire; Wellington, Elizabeth; Miller, Woutrina A; Travis, Emma; Porter, David; Cooper, David; Clifford, Deana L; Mazet, Jonna A K; Parsons, Sven

2014-01-01

A real-time PCR protocol for detecting Mycobacterium bovis in feces was evaluated in bovine tuberculosis-infected African buffalo (Syncerus caffer). Fecal samples spiked with 1.42 × 10(3) cells of M. bovis culture/g and Bacille Calmette-Guérin standards with 1.58 × 10(1) genome copies/well were positive by real-time PCR but all field samples were negative.

Human respiratory syncytial virus in children with lower respiratory tract infections or influenza-like illness and its co-infection characteristics with viruses and atypical bacteria in Hangzhou, China.

PubMed

Yu, Xinfen; Kou, Yu; Xia, Daozong; Li, Jun; Yang, Xuhui; Zhou, Yinyan; He, Xiaoyan

2015-08-01

Human respiratory syncytial virus (RSV) is the most important viral pathogen in children. However, its epidemic patterns and co-infection characteristics are not fully understood. We attempted to determine the level of genetic variation of RSV, and describe the prevalence and co-infection characteristics of RSV in Hangzhou during two epidemic seasons. Single respiratory samples from 1820 pediatric patients were screened for RSV and genotyped by RT-PCR and sequencing. In all RSV positive specimens, we screened for viruses and atypical bacteria. Demographic and clinical information was recorded and analyzed. A total of 34.5% and 3.8% of samples from acute lower respiratory tract infections (ALRI) and influenza-like illness (ILI) were positive for RSV, respectively. Phylogenetic analysis revealed that 61.1% of the selected 167 RSV strains were NA1, 31.1% were BA, 3.6% were ON1, 2.4% were CB1, and 1.8% were NA3. A new genotype, BA11 was identified, which comprised 98.1% of BA strains in this study, while the rest were BA10. A total of 36.4% and 9.1% of RSV-positive children with ALRI and ILI respectively were found to be co-infected. Rhinovirus was the most common additional respiratory virus, followed by human metapneumovirus. Except for fever, no significant differences in other clinical presentation between the RSV mono-infection and co-infection groups were observed. The circulating RSV strains had high genetic variability with RSV-B showing a more local pattern. In ALRI cases, co-infection of RSV with other viruses or atypical bacteria has no significant effect on the clinical presentation except fever. Copyright © 2015 Elsevier B.V. All rights reserved.

Challenges and perspectives for improved management of HIV/Mycobacterium tuberculosis co-infection.

PubMed

Sester, M; Giehl, C; McNerney, R; Kampmann, B; Walzl, G; Cuchí, P; Wingfield, C; Lange, C; Migliori, G B; Kritski, A L; Meyerhans, A

2010-12-01

HIV and Mycobacterium tuberculosis (MTB) are two widespread and highly successful microbes whose synergy in pathogenesis has created a significant threat for human health globally. In acknowledgement of this fact, the European Union (EU) has funded a multinational support action, the European Network for global cooperation in the field of AIDS and TB (EUCO-Net), that brings together experts from Europe and those regions that bear the highest burden of HIV/MTB co-infection. Here, we summarise the main outcome of the EUCO-Net project derived from an expert group meeting that took place in Stellenbosch (South Africa) (AIDS/TB Workshop on Research Challenges and Opportunities for Future Collaboration) and the subsequent discussions, and propose priority areas for research and concerted actions that will have impact on future EU calls.

Mycobacterium tuberculosis infection in cattle from the Eastern Cape Province of South Africa.

PubMed

Hlokwe, Tiny Motlatso; Said, Halima; Gcebe, Nomakorinte

2017-10-10

Mycobacterium tuberculosis is the main causative agent of tuberculosis (TB) in human and Mycobacterium bovis commonly causes tuberculosis in animals. Transmission of tuberculosis caused by both pathogens can occur from human to animals and vice versa. In the current study, M. tuberculosis, as confirmed by polymerase chain reaction (PCR) using primers targeting 3 regions of difference (RD4, RD9 and RD12) on the genomes, was isolated from cattle originating from two epidemiologically unrelated farms in the Eastern Cape (E.C) Province of South Africa. Although the isolates were genotyped with variable number of tandem repeat (VNTR) typing, no detailed epidemiological investigation was carried out on the respective farms to unequivocally confirm or link humans as sources of TB transmission to cattle, a move that would have embraced the 'One Health' concept. In addition, strain comparison with human M. tuberculosis in the database from the E.C Province and other provinces in the country did not reveal any match. This is the first report of cases of M. tuberculosis infection in cattle in South Africa. The VNTR profiles of the M. tuberculosis strains identified in the current study will form the basis for creating M. tuberculosis VNTR database for animals including cattle for future epidemiological studies. Our findings however, call for urgent reinforcement of collaborative efforts between the veterinary and the public health services of the country.

The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.

PubMed

Correa, Andre F; Bailão, Alexandre M; Bastos, Izabela M D; Orme, Ian M; Soares, Célia M A; Kipnis, Andre; Santana, Jaime M; Junqueira-Kipnis, Ana Paula

2014-12-01

Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Immunoreactivity of protein tyrosine phosphatase A (PtpA) in sera from sheep infected with Mycobacterium avium subspecies paratuberculosis.

PubMed

Gurung, Ratna B; Begg, Douglas J; Purdie, Auriol C; Bach, Horacio; Whittington, Richard J

2014-07-15

Evasion of host defense mechanisms and survival inside infected host macrophages are features of pathogenic mycobacteria including Mycobacterium avium subspecies paratuberculosis, the causative agent of Johne's disease in ruminants. Protein tyrosine phosphatase A (PtpA) has been identified as a secreted protein critical for survival of mycobacteria within infected macrophages. The host may mount an immune response to such secreted proteins. In this study, the humoral immune response to purified recombinant M. avium subsp. paratuberculosis PtpA was investigated using sera from a cohort of sheep infected with M. avium subsp. paratuberculosis and compared with uninfected healthy controls. A significantly higher level of reactivity to PtpA was observed in sera collected from M. avium subspecies paratuberculosis infected sheep when compared to those from uninfected healthy controls. PtpA could be a potential candidate antigen for detection of humoral immune responses in sheep infected with M. avium subspecies paratuberculosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Exit Site Infection due to Mycobacterium chelonae in an Elderly Patient on Peritoneal Dialysis.

PubMed

Hibi, Arata; Kasugai, Takahisa; Kamiya, Keisuke; Ito, Chiharu; Kominato, Satoru; Miura, Toshiyuki; Koyama, Katsushi

2018-01-01

Nontuberculous mycobacteria (NTM) are rarely isolated from peritoneal dialysis (PD)-associated catheter infections. However, NTM infection is usually difficult to treat and leads to catheter loss. Prompt diagnosis is essential for appropriate treatment. A 70-year-old Japanese man who had been on PD for 2 years and with a medical history of 2 episodes of exit site infections (ESIs) due to methicillin-resistant Staphylococcus aureus was admitted to the hospital due to suspected ESI recurrence. However, Gram staining of the pus revealed no gram-positive cocci. Instead, weakly stained gram-positive rods were observed after 7 days of incubation, which were also positive for acid-fast staining. Rapidly growing NTM Mycobacterium chelonae was isolated on day 14. Despite administering a combination antibiotic therapy, ESI could not be controlled, and catheter removal surgery was performed on day 21. Although PD was discontinued temporarily, the patient did not require hemodialysis, without any uremic symptoms. The catheter was reinserted on day 48, and PD was reinitiated on day 61. The patient was discharged on day 65. Antibiotic therapy was continued for 3 months after discharge, with no indications of recurrent infections observed. It is important to consider the risk of NTM infections in patients on PD. Acid-fast staining could be a key test for prompt diagnosis and provision of an appropriate treatment.

Dose-response association between salivary cotinine levels and Mycobacterium tuberculosis infection.

PubMed

Shin, S S; Laniado-Laborin, R; Moreno, P G; Novotny, T E; Strathdee, S A; Garfein, R S

2013-11-01

Tijuana, Mexico. To describe the association between salivary cotinine levels and interferon-gamma (IFN-γ) release assay results. We conducted a cross-sectional study among injection drug users. Salivary cotinine levels were measured using NicAlert, a semi-quantitative dipstick assay. QuantiFERON©-TB Gold In-Tube (QFT-GIT) was used to determine Mycobacterium tuberculosis infection. Among 234 participants, the prevalence of QFT-GIT positivity for NicAlert cotinine categories 0 (non-smoking), 1 (second-hand smoke exposure or low-level smoking) and 26 (regular smoking) were respectively 42.1%, 46.4% and 65.2% (Ptrend 0.012). We found increasing trends in QFT-GIT positivity (Ptrend 0.003) and IFN-γ concentrations (Spearman's r 0.200, P 0.002) across cotinine levels 0 to 6. In multivariable log-binomial regression models adjusted for education, cotinine levels were not associated with QFT-GIT positivity when included as smoking categories (1 and 26 vs. 0), but were independently associated with QFT-GIT positivity when included as an ordinal variable (prevalence ratio 1.09 per 1 cotinine level, 95%CI 1.021.16). Our findings suggest that a dose-response relationship exists between tobacco smoke exposure and M. tuberculosis infection. Longitudinal studies that use biochemical measures for smoking status are needed to confirm our findings.

Ultra-low dose of Mycobacterium tuberculosis aerosol creates partial infection in mice.

PubMed

Saini, Divey; Hopkins, Gregory W; Seay, Sarah A; Chen, Ching-Ju; Perley, Casey C; Click, Eva M; Frothingham, Richard

2012-03-01

A murine low dose (LD) aerosol model is commonly used to test tuberculosis vaccines. Doses of 50-400 CFU (24h lung CFU) infect 100% of exposed mice. The LD model measures progression from infection to disease based on organ CFU at defined time points. To mimic natural exposure, we exposed mice to an ultra-low dose (ULD) aerosol. We estimated the presented dose by sampling the aerosol. Female C57BL/6 mice were exposed to Mycobacterium tuberculosis H37Rv aerosol at 1.0, 1.1, 1.6, 5.4, and 11 CFU presented dose, infecting 27%, 36%, 36%, 100%, and 95% of mice, respectively. These data are compatible with a stochastic infection event (Poisson distribution, weighted R(2)=0.97) or with a dose-response relationship (sigmoid distribution, weighted R(2)=0.97). Based on the later assumption, the ID50 was 1.6CFU presented dose (95% confidence interval, 1.2-2.1). We compared organ CFU after ULD and LD aerosols (5.4 vs. 395CFU presented dose). Lung burden was 30-fold lower in the ULD model at 4 weeks (3.4 vs. 4.8 logs, p<0.001) and 18 weeks (≤3.6 vs. 5.0 logs, p=0.01). Mice exposed to ULD aerosols as compared to LD aerosols had greater within-group CFU variability. Exposure to ULD aerosols leads to infection in a subset of mice, and to persistently low organ CFU. The ULD aerosol model may resemble human pulmonary tuberculosis more closely than the standard LD model, and may be used to identify host or bacterial factors that modulate the initial infection event. Copyright © 2011 Elsevier Ltd. All rights reserved.

Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model.

PubMed

Trigo, Gabriela; Martins, Teresa G; Fraga, Alexandra G; Longatto-Filho, Adhemar; Castro, António G; Azeredo, Joana; Pedrosa, Jorge

2013-01-01

Buruli Ulcer (BU) is a neglected, necrotizing skin disease caused by Mycobacterium ulcerans. Currently, there is no vaccine against M. ulcerans infection. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages is still based on the surgical resection of infected skin. The use of bacteriophages for the control of bacterial infections has been considered as an alternative or to be used in association with antibiotherapy. Additionally, the mycobacteriophage D29 has previously been shown to display lytic activity against M. ulcerans isolates. We used the mouse footpad model of M. ulcerans infection to evaluate the therapeutic efficacy of treatment with mycobacteriophage D29. Analyses of macroscopic lesions, bacterial burdens, histology and cytokine production were performed in both M. ulcerans-infected footpads and draining lymph nodes (DLN). We have demonstrated that a single subcutaneous injection of the mycobacteriophage D29, administered 33 days after bacterial challenge, was sufficient to decrease pathology and to prevent ulceration. This protection resulted in a significant reduction of M. ulcerans numbers accompanied by an increase of cytokine levels (including IFN-γ), both in footpads and DLN. Additionally, mycobacteriophage D29 treatment induced a cellular infiltrate of a lymphocytic/macrophagic profile. Our observations demonstrate the potential of phage therapy against M. ulcerans infection, paving the way for future studies aiming at the development of novel phage-related therapeutic approaches against BU.

Systemic and Mucosal Immune Reactivity upon Mycobacterium avium ssp. paratuberculosis Infection in Mice

PubMed Central

Suwandi, Abdulhadi; Roderfeld, Martin; Tschuschner, Annette; Rath, Timo; Gerlach, Gerald F.; Hornef, Mathias; Goethe, Ralph; Weiss, Siegfried; Roeb, Elke

2014-01-01

Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease, an inflammatory bowel disorder of ruminants. Due to the similar pathology, MAP was also suggested to cause Crohn's disease (CD). Despite of intensive research, this question is still not settled, possibly due to the lack of versatile mouse models. The aim of this study was to identify basic immunologic mechanisms in response to MAP infection. Immune compromised C57BL/6 Rag2 −/− mice were infected with MAP intraperitoneally. Such chronically infected mice were then reconstituted with CD4+ and CD8+ T cells 28 days after infection. A systemic inflammatory response, detected as enlargement of the spleen and granuloma formation in the liver, was observed in mice infected and reconstituted with CD4+ T cells. Whereby inflammation in infected and CD4+CD45RBhi T cell reconstituted animals was always higher than in the other groups. Reconstitution of infected animals with CD8+ T cells did not result in any inflammatory signs. Interestingly, various markers of inflammation were strongly up-regulated in the colon of infected mice reconstituted with CD4+CD45RBlo/int T cells. We propose, the usual non-colitogenic CD4+CD45RBlo/int T cells were converted into inflammatory T cells by the interaction with MAP. However, the power of such cells might be not sufficient for a fully established inflammatory response in the colon. Nevertheless, our model system appears to mirror aspects of an inflammatory bowel disease (IBD) like CD and Johne's diseases. Thus, it will provide an experimental platform on which further knowledge on IBD and the involvement of MAP in the induction of CD could be acquired. PMID:24728142

Clofazimine Modulates the Expression of Lipid Metabolism Proteins in Mycobacterium leprae-Infected Macrophages

PubMed Central

Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

2012-01-01

Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine. PMID:23236531

Systemic and mucosal immune reactivity upon Mycobacterium avium ssp. paratuberculosis infection in mice.

PubMed

Koc, Arzu; Bargen, Imke; Suwandi, Abdulhadi; Roderfeld, Martin; Tschuschner, Annette; Rath, Timo; Gerlach, Gerald F; Hornef, Mathias; Goethe, Ralph; Weiss, Siegfried; Roeb, Elke

2014-01-01

Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease, an inflammatory bowel disorder of ruminants. Due to the similar pathology, MAP was also suggested to cause Crohn's disease (CD). Despite of intensive research, this question is still not settled, possibly due to the lack of versatile mouse models. The aim of this study was to identify basic immunologic mechanisms in response to MAP infection. Immune compromised C57BL/6 Rag2-/- mice were infected with MAP intraperitoneally. Such chronically infected mice were then reconstituted with CD4+ and CD8+ T cells 28 days after infection. A systemic inflammatory response, detected as enlargement of the spleen and granuloma formation in the liver, was observed in mice infected and reconstituted with CD4+ T cells. Whereby inflammation in infected and CD4+CD45RB(hi) T cell reconstituted animals was always higher than in the other groups. Reconstitution of infected animals with CD8+ T cells did not result in any inflammatory signs. Interestingly, various markers of inflammation were strongly up-regulated in the colon of infected mice reconstituted with CD4+CD45RB(lo/int) T cells. We propose, the usual non-colitogenic CD4+CD45RB(lo/int) T cells were converted into inflammatory T cells by the interaction with MAP. However, the power of such cells might be not sufficient for a fully established inflammatory response in the colon. Nevertheless, our model system appears to mirror aspects of an inflammatory bowel disease (IBD) like CD and Johne's diseases. Thus, it will provide an experimental platform on which further knowledge on IBD and the involvement of MAP in the induction of CD could be acquired.

Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages.

PubMed

Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

2012-01-01

Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.

Mycobacterium bovis in Panama, 2013

PubMed Central

Acosta, Fermín; Chernyaeva, Ekatherina; Mendoza, Libardo; Sambrano, Dilcia; Correa, Ricardo; Rotkevich, Mikhail; Tarté, Miroslava; Hernández, Humberto; Velazco, Bredio; de Escobar, Cecilia; de Waard, Jacobus H.

2015-01-01

Panama remains free of zoonotic tuberculosis caused by Mycobacterium bovis. However, DNA fingerprinting of 7 M. bovis isolates from a 2013 bovine tuberculosis outbreak indicated minimal homology with strains previously circulating in Panama. M. bovis dispersion into Panama highlights the need for enhanced genotype testing to track zoonotic infections. PMID:25988479

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis-Infected Macrophages

PubMed Central

Barrow, Esther L. W.; Winchester, Gary A.; Staas, Jay K.; Quenelle, Debra C.; Barrow, William W.

1998-01-01

Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of Mycobacterium tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing M. tuberculosis intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages. PMID:9756777

Evidence of disseminated infection by Mycobacterium avium subspecies hominissuis in a pet ferret (Mustela putorius furo).

PubMed

Bezos, Javier; Álvarez-Carrión, Beatriz; Rodríguez-Bertos, Antonio; Fernández-Manzano, Álvaro; de Juan, Lucía; Huguet, Cristina; Briones, Víctor; Romero, Beatriz

2016-12-01

The infection caused by the zoonotic opportunistic pathogen Mycobacterium avium subsp. hominissuis (Mah) was reported for the first time in a pet ferret. Both owners were HIV-positive. Euthanasia of the pet was recommended due to medical reasons and as a preventive action. Disseminated and open tuberculosis lesions were observed in the gastrointestinal and respiratory systems of the ferret. Ecographic and radiographic surveys showed a severe generalized lymphadenopathy, strong thickening of the gastric wall and peritoneum layer. The histopathological findings revealed a disseminated, granulomatous, chronic inflammation affecting the gastrointestinal tract, lungs, lymphoid tissues (spleen, tonsils and lymph nodes) and liver. Ziehl-Neelsen staining displayed the presence of positive acid-fast bacilli within these granulomas. Bacteriology and sequencing of the isolates yielded Mah sequevar code 3. Ferrets can act as reservoirs of mycobacteria exposing their owners to the infection, which is of major concern in immunodeficient individuals, as those HIV-infected. Copyright © 2016 Elsevier Ltd. All rights reserved.

A naturally occurring cowpox virus with an ectromelia virus A-type inclusion protein gene displays atypical A-type inclusions.

PubMed

Okeke, Malachy Ifeanyi; Hansen, Hilde; Traavik, Terje

2012-01-01

Human orthopoxvirus (OPV) infections in Europe are usually caused by cowpox virus (CPXV). The genetic heterogeneity of CPXVs may in part be due to recombination with other OPV species. We describe the characterization of an atypical CPXV (CPXV-No-H2) isolated from a human patient in Norway. CPXV-No-H2 was characterized on the basis of A-type inclusion (ATI) phenotype as well as the DNA region containing the p4c and atip open reading frames. CPXV-No-H2 produced atypical V(+/) ATI, in which virions are on the surface of ATI but not within the ATI matrix. Phylogenetic analysis showed that the atip gene of CPXV-No-H2 clustered closely with that of ectromelia virus (ECTV) with a bootstrap support of 100% whereas its p4c gene is diverged compared to homologues in other OPV species. By recombination analysis we identified a putative crossover event at nucleotide 147, downstream the start of the atip gene. Our results suggest that CPXV-No-H2 originated from a recombination between CPXV and ECTV. Our findings are relevant to the evolution of OPVs. Copyright © 2011 Elsevier B.V. All rights reserved.

Prevalence of latent Mycobacterium tuberculosis infection in prisoners.

PubMed

Navarro, Pedro Daibert de; Almeida, Isabela Neves de; Kritski, Afrânio Lineu; Ceccato, Maria das Graças; Maciel, Mônica Maria Delgado; Carvalho, Wânia da Silva; Miranda, Silvana Spindola de

2016-01-01

To determine the prevalence of and the factors associated with latent Mycobacterium tuberculosis infection (LTBI) in prisoners in the state of Minas Gerais, Brazil. This was a cross-sectional cohort study conducted in two prisons in Minas Gerais. Tuberculin skin tests were performed in the individuals who agreed to participate in the study. A total of 1,120 individuals were selected for inclusion in this study. The prevalence of LTBI was 25.2%. In the multivariate analysis, LTBI was associated with self-reported contact with active tuberculosis patients within prisons (adjusted OR = 1.51; 95% CI: 1.05-2.18) and use of inhaled drugs (adjusted OR = 1.48; 95% CI: 1.03-2.13). Respiratory symptoms were identified in 131 (11.7%) of the participants. Serological testing for HIV was performed in 940 (83.9%) of the participants, and the result was positive in 5 (0.5%). Two cases of active tuberculosis were identified during the study period. Within the prisons under study, the prevalence of LTBI was high. In addition, LTBI was associated with self-reported contact with active tuberculosis patients and with the use of inhaled drugs. Our findings demonstrate that it is necessary to improve the conditions in prisons, as well as to introduce strategies, such as chest X-ray screening, in order to detect tuberculosis cases and, consequently, reduce M. tuberculosis infection within the prison system. Determinar a prevalência e os fatores associados à infecção latente por Mycobacterium tuberculosis (ILTB) em pessoas privadas de liberdade no Estado de Minas Gerais. Estudo de coorte transversal realizado em duas penitenciárias em Minas Gerais. Foi realizada a prova tuberculínica nos indivíduos que aceitaram participar do estudo. Foram selecionados 1.120 indivíduos para a pesquisa. A prevalência da ILTB foi de 25,2%. Na análise multivariada, a ILTB esteve associada com relato de contato com caso de tuberculose ativa dentro da penitenciária (OR ajustada = 1,51; IC95%: 1

Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease.

PubMed

Guggino, Giuliana; Orlando, Valentina; Cutrera, Stella; La Manna, Marco P; Di Liberto, Diana; Vanini, Valentina; Petruccioli, Elisa; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia

2015-08-01

Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

PPAR-γ and Akt regulate GLUT1 and GLUT3 surface localization during Mycobacterium tuberculosis infection.

PubMed

Dasgupta, Shyamashree; Rai, Ramesh Chandra

2018-03-01

The success of Mycobacterium tuberculosis (Mtb) as a pathogen stems from its ability to manipulate the host macrophage towards increased lipid biogenesis and lipolysis inhibition. Inhibition of lipolysis requires augmented uptake of glucose into the host cell causing an upregulation of the glucose transporters GLUT1 and GLUT3 on the cell surface. Mechanism behind this upregulation of the GLUT proteins during Mtb infection is hitherto unknown and demands intensive investigation in order to understand the pathways linked with governing them. Our endeavor to investigate some of the key proteins that have been found to be affected during Mtb infection led us to investigate host molecular pathways such as Akt and PPAR-γ that remain closely associated with the survival of the bacilli by modulating the localization of glucose transporters GLUT1 and GLUT3.

Mycobacterium komaniense sp. nov., a rapidly growing non-tuberculous Mycobacterium species detected in South Africa.

PubMed

Gcebe, Nomakorinte; Rutten, Victor P M G; van Pittius, Nicolaas Gey; Naicker, Brendon; Michel, Anita L

2018-05-01

Some species of non-tuberculous mycobacteria (NTM) have been reported to be opportunistic pathogens of animals and humans. Recently there has been an upsurge in the number of cases of NTM infections, such that some NTM species are now recognized as pathogens of humans and animals. From a veterinary point of view, the major significance of NTM is the cross-reactive immune response they elicit against Mycobacterium bovis antigens, leading to misdiagnosis of bovine tuberculosis. Four NTM isolates were detected from a bovine nasal swab, soil and water, during an NTM survey in South Africa. These were all found using 16S rRNA gene sequence analysis to be closely related to Mycobacterium moriokaense. The isolates were further characterised by sequence analysis of the partial fragments of hsp65, rpoB and sodA. The genome of the type strain was also elucidated. Gene (16S rRNA, hsp65, rpoB and sodA) and protein sequence data analysis of 6 kDa early secretory antigenic target (ESAT 6) and 10 kDa culture filtrate protein (CFP-10) revealed that these isolates belong to a unique Mycobacterium species. Differences in phenotypic and biochemical traits between the isolates and closely related species further supported that these isolates belong to novel Mycobacterium species. We proposed the name Mycobacterium komaniense sp. nov. for this new species. The type strain is GPK 1020 T (=CIP 110823T=ATCC BAA-2758).

Detection of Mycobacterium avium in pet birds

PubMed Central

Godoy, Silvia Neri; Sakamoto, Sidnei Miyoshi; de Paula, Cátia Dejuste; Catão-Dias, José Luiz; Matushima, Eliana Reiko

2009-01-01

The present study is a report on the presence of Mycobacterium avium in four birds of the psittaciform order kept as pets. Anatomopathological diagnosis showed lesions suggestive of the agent and presence of alcohol-acid resistant bacilli (AARB) shown by the Ziehl-Neelsen staining. The identification of Mycobacterium avium was performed by means of PRA (PCR Restriction Analysis). DNA was directly extracted from tissue of the lesions and blocked in paraffin. The role of this agent in pet bird infection is discussed, as well as its zoonotic potential. PMID:24031356

Immune Responses in Cattle Inoculated with Mycobacterium bovis, Mycobacterium tuberculosis, or Mycobacterium kansasii

USDA-ARS?s Scientific Manuscript database

Cattle were inoculated with Mycobacterium bovis, Mycobacterium tuberculosis, or Mycobacterium kansasii to compare antigen-specific immune responses to varied patterns of mycobacterial disease. Disease expression ranged from colonization with associated pathology (M. bovis), colonization without path...

Mycobacterium bovis infection in the lion (Panthera leo): Current knowledge, conundrums and research challenges.

PubMed

Viljoen, Ignatius M; van Helden, Paul D; Millar, Robert P

2015-06-12

Mycobacterium bovis has global public-health and socio-economic significance and can infect a wide range of species including the lion (Panthera leo) resulting in tuberculosis. Lions are classified as vulnerable under the IUCN Red List of Threatened Species and have experienced a 30% population decline in the past two decades. However, no attempt has been made to collate and critically evaluate the available knowledge of M. bovis infections in lions and potential effects on population. In this review we set out to redress this. Arguments suggesting that ingestion of infected prey animals are the main route of infection for lions have not been scientifically proven and research is needed into other possible sources and routes of infection. The paucity of knowledge on host susceptibility, transmission directions and therefore host status, manifestation of pathology, and epidemiology of the disease in lions also needs to be addressed. Advances have been made in diagnosing the presence of M. bovis in lions. However, these diagnostic tests are unable to differentiate between exposure, presence of infection, or stage of disease. Furthermore, there are contradictory reports on the effects of M. bovis on lion populations with more data needed on disease dynamics versus the lion population's reproductive dynamics. Knowledge on disease effects on the lion reproduction and how additional stressors such as drought or co-morbidities may interact with tuberculosis is also lacking. Filling these knowledge gaps will contribute to the understanding of mycobacterial infections and disease in captive and wild lions and assist in lion conservation endeavours. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid susceptibility testing of Mycobacterium avium complex and Mycobacterium tuberculosis isolated from AIDS patients

NASA Technical Reports Server (NTRS)

Dhople, Arvind M.

1994-01-01

In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of HIV infection will continue to rise more rapidly worldwide than predicted earlier. The AIDS patients are susceptible to diseases called opportunistic infections of which tuberculosis and Mycobacterium avium complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, MD, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. We proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis.

Antemortem diagnosis of Mycobacterium bovis infection in free-ranging African lions (Panthera leo) and implications for transmission.

PubMed

Miller, Michele; Buss, Peter; Hofmeyr, Jennifer; Olea-Popelka, Francisco; Parsons, Sven; van Helden, Paul

2015-04-01

Diagnosis of tuberculosis in wildlife often relies on postmortem samples because of logistical challenges and lack of field-friendly techniques for live animal testing. Confirmation of infection through detection of infectious organisms is essential for studying the pathogenesis and epidemiology of disease. We describe the application of a technique to obtain respiratory samples from free-ranging living lions to facilitate detection of viable Mycobacterium bovis under field conditions. We identified M. bovis by mycobacterial culture and PCR in tracheobronchial lavage samples from 8/134 (6.0%) lions tested in Kruger National Park, South Africa. This confirms the respiratory shedding of viable M. bovis in living lions. The implications of these results are that infected lions have the potential to transmit this disease and serve as maintenance hosts.

IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

PubMed

Hu, Shengfeng; He, Wenting; Du, Xialin; Yang, Jiahui; Wen, Qian; Zhong, Xiao-Ping; Ma, Li

2017-09-01

To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and EKR in neutrophils. Furthermore, we found that Toll-like receptor 2 (TLR2) and TLR4 mediated the activation of the kinases NF-κB, p38, ERK, and JNK and the production of IL-6, IL-23, and IL-17 in neutrophils infected with MTB H37Rv. Autocrine IL-17 produced by neutrophils played a vital role in inhibiting MTB H37Rv growth by mediating reactive oxygen species production and the migration of neutrophils in the early stages of infection. However, IL-17 production by neutrophils contributed to collagen-induced arthritis development during MTB infection. Our findings identify a protective mechanism against mycobacteria and the pathogenic role of MTB in arthritis development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Pediatric Dental Clinic-Associated Outbreak of Mycobacterium abscessus Infection.

PubMed

Hatzenbuehler, Lindsay A; Tobin-D'Angelo, Melissa; Drenzek, Cherie; Peralta, Gianna; Cranmer, Lisa C; Anderson, Evan J; Milla, Sarah S; Abramowicz, Shelly; Yi, Jumi; Hilinski, Joseph; Rajan, Roy; Whitley, Matthew K; Gower, Verlia; Berkowitz, Frank; Shapiro, Craig A; Williams, Joseph K; Harmon, Paula; Shane, Andi L

2017-09-01

Mycobacterium abscessus is an uncommon cause of invasive odontogenic infection. M abscessus-associated odontogenic infections occurred in a group of children after they each underwent a pulpotomy. A probable case-child was defined as a child with facial or neck swelling and biopsy-confirmed granulomatous inflammation after a pulpotomy between October 1, 2013, and September 30, 2015. M abscessus was isolated by culture in confirmed case-children. Clinical presentation, management, and outcomes were determined by medical record abstraction. Among 24 children, 14 (58%) were confirmed case-children. Their median age was 7.3 years (interquartile range, 5.8-8.2 years), and the median time from pulpotomy to symptom onset was 74 days (range, 14-262 days). Clinical diagnoses included cervical lymphadenitis (24 [100%] of 24), mandibular or maxillary osteomyelitis (11 [48%] of 23), and pulmonary nodules (7 [37%] of 19). Each child had ≥1 hospitalization and a median of 2 surgeries (range, 1-6). Of the 24 children, 12 (50%) had surgery alone and 11 (46%) received intravenous (IV) antibiotics. Nineteen of the 24 (79%) children experienced complications, including vascular access malfunction (7 [64%] of 11), high-frequency hearing loss (5 [56%] of 9), permanent tooth loss (11 [48%] of 23), facial nerve palsy (7 [29%] of 24), urticarial rash (3 [25%] of 12), elevated liver enzyme levels (1 [20%] of 5), acute kidney injury (2 [18%] of 11), incision dehiscence/fibrosis (3 [13%] of 24), and neutropenia (1 [9%] of 11). M abscessus infection was associated with significant medical morbidity and treatment complications. Unique manifestations included extranodal mandibular or maxillary osteomyelitis and pulmonary nodules. Challenges in the identification of case-children resulted from an extended incubation period and various clinical manifestations. Clinicians should consider the association between M abscessus infection and pulpotomy in children who present with subacute cervical

Atypical Skeletal Muscle Profiles in Human Immunodeficiency Virus-Infected Asymptomatic Middle-Aged Adults.

PubMed

Tran, Thanh; Guardigni, Viola; Pencina, Karol M; Amato, Anthony A; Floyd, Michael; Brawley, Brooke; Mozeleski, Brian; McKinnon, Jennifer; Woodbury, Erin; Heckel, Emily; Li, Zhuoying; Storer, Tom; Sax, Paul E; Montano, Monty

2018-06-01

Human immunodeficiency virus (HIV)-infected individuals are at increased risk of age-associated functional impairment, even with effective antiretroviral therapy (ART). A concurrent characterization of skeletal muscle, physical function, and immune phenotype in aviremic middle-aged HIV-infected adults represents a knowledge gap in prognostic biomarker discovery. We undertook a prospective observational study of 170 middle-aged, HIV-infected ambulatory men and women with CD4+ T-cell counts of at least 350/µL and undetectable plasma viremia while on effective ART, and uninfected control participants. We measured biomarkers for inflammation and immune activation, fatigue, the Veterans Aging Cohort Study mortality index, and physical function. A subset also received a skeletal muscle biopsy and computed tomography scan. Compared to the uninfected participants, HIV-infected participants displayed increased immune activation (P < .001), inflammation (P = .001), and fatigue (P = .010), and in a regression model adjusting for age and sex displayed deficits in stair-climb power (P < .001), gait speed (P = .036), and predicted metabolic equivalents (P = .019). Skeletal muscle displayed reduced nuclear peroxisome proliferator-activated receptor-γ coactivator 1α-positive myonuclei (P = .006), and increased internalized myonuclei (P < .001) that correlated with immune activation (P = .003) and leukocyte infiltration (P < .001). Internalized myonuclei improved a model for HIV discrimination, increasing the C-statistic from 0.84 to 0.90. Asymptomatic HIV-infected middle-aged adults display atypical skeletal muscle profiles, subclinical deficits in physical function, and persistent inflammation and immune activation. Identifying biomarker profiles for muscle dysregulation and risk for future functional decline in the HIV-infected population will be key to developing and monitoring preventive interventions. NCT03011957.

Mycobacterium haemophilum infection in a juvenile leatherback sea turtle (Dermochelys coriacea).

PubMed

Donnelly, Kyle; Waltzek, Thomas B; Wellehan, James F X; Stacy, Nicole I; Chadam, Maria; Stacy, Brian A

2016-11-01

Mycobacteriosis is infrequently reported in free-ranging sea turtles. Nontuberculous Mycobacterium haemophilum was identified as the causative agent of disseminated mycobacteriosis in a juvenile leatherback turtle (Dermochelys coriacea) that was found stranded on the Atlantic coast of Florida. Disseminated granulomatous inflammation was identified histologically, most notably affecting the nervous system. Identification of mycobacterial infection was based on cytologic, molecular, histologic, and microbiologic methods. Among stranded sea turtles received for diagnostic evaluation from the Atlantic and Gulf of Mexico coasts of the United States between 2004 and 2015, the diagnosis of mycobacteriosis was overrepresented in stranded oceanic-phase juveniles compared with larger size classes, which suggests potential differences in susceptibility or exposure among different life phases in this region. We describe M. haemophilum in a sea turtle, which contributes to the knowledge of diseases of small juvenile sea turtles, an especially cryptic life phase of the leatherback turtle. © 2016 The Author(s).

Gamma Interferon-Induced T-Cell Loss in Virulent Mycobacterium avium Infection

PubMed Central

Flórido, Manuela; Pearl, John E.; Solache, Alejandra; Borges, Margarida; Haynes, Laura; Cooper, Andrea M.; Appelberg, Rui

2005-01-01

Infection by virulent Mycobacterium avium caused progressive severe lymphopenia in C57BL/6 mice due to increased apoptosis rates. T-cell depletion did not occur in gamma interferon (IFN-γ)-deficient mice which showed increased T-cell numbers and proliferation; in contrast, deficiency in nitric oxide synthase 2 did not prevent T-cell loss. Although T-cell loss was IFN-γ dependent, expression of the IFN-γ receptor on T cells was not required for depletion. Similarly, while T-cell loss was optimal if the T cells expressed IFN-γ, CD8+ T-cell depletion could occur in the absence of T-cell-derived IFN-γ. Depletion did not require that the T cells be specific for mycobacterial antigen and was not affected by deficiencies in the tumor necrosis factor receptors p55 or p75, the Fas receptor (CD95), or the respiratory burst enzymes or by forced expression of bcl-2 in hematopoietic cells. PMID:15908387

Characterization of mycobacteria in HIV/AIDS patients of Nepal.

PubMed

Dhungana, G P; Ghimire, P; Sharma, S; Rijal, B P

2008-01-01

Besides Mycobacterium tuberculosis, a number of other Mycobacterium species are also occasional human pathogens. Tuberculosis due to Mycobacterium avium complex (MAC) and Mycobacterium kansasii is particularly prevalent in AIDS patients as compared to the normal population. A cross-sectional study was carried out during January 2004 to August 2005 in 100 HIV-infected persons visiting Tribhuvan University, Teaching Hospital, and about a dozen of HIV/AIDS care centers of Kathmandu with the objectives to characterize the different mycobacterial species in HIV/AIDS patients. Three sputum specimens from each person were used to investigate tuberculosis by Ziehl-Neelsen staining, culture and identification tests. Among the 100 HIV-infected cases, 66 (66%) were males and 34 (34%) were females. Sixty percent of the cases were in the age group of 21-30 years. Mycobacteria were detected in 23 (23%) HIV cases of which 15 (65.2%) were in the age group of 21-30 years ; 17(74%) were males and 6 (26 %) were females. Among 23 co-infected cases, 22 were culture positive for mycobacteria. Among these, the predominant one was Mycobacterium avium complex (MAC), 9 (41%), followed by M. tuberculosis, 6 (27%), M .kansasii, 4 (18%), M. fortuitum, 2 (10%) and M. chelonae 1 (4%). Significant relationship was established between smoking/alcoholism and the subsequent development of tuberculosis (chi(2)=7.24, p<0.05 for smoking habit and chi(2)=4.39, p<0.05 for alcoholism). Fourteen (61%) co-infected cases presented with weight loss and cough whereas diarrhea was presented only by those patients with atypical mycobacterial co-infection, which was as high as 5 (56%) in patients with MAC co-infection. This study demonstrated the predominance of atypical mycobacteria, mainly MAC, in HIV/AIDS cases and most of them were from sputum smear-negative cases.

Low cross-reactivity of T-cell responses against lipids from Mycobacterium bovis and M. avium paratuberculosis during natural infection

PubMed Central

Van Rhijn, Ildiko; Nguyen, Thi Kim Anh; Michel, Anita; Cooper, Dave; Govaerts, Marc; Cheng, Tan-Yun; van Eden, Willem; Moody, D. Branch; Coetzer, Jacobus A. W.; Rutten, Victor; Koets, Ad P.

2011-01-01

Although CD1 proteins are known to present mycobacterial lipid antigens to T cells, there is little understanding of the in vivo behavior of T cells restricted by CD1a, CD1b and CD1c, and the relative immunogenicity and immunodominance of individual lipids within the total array of lipids that comprise a bacterium. Because bovines express multiple CD1 proteins and are natural hosts of Mycobacterium bovis and Mycobacterium avium paratuberculosis (MAP), we used them as a new animal model of CD1 function. Here, we report the surprisingly divergent responses against lipids produced by these two pathogens during infection. Despite considerable overlap in lipid content, only three out of 69 animals cross-react with M. bovis and MAP total lipid preparations. The unidentified immunodominant compound of M. bovis is a hydrophilic compound, whereas the immunodominant lipid of MAP is presented by CD1b and was identified as glucose monomycolate (GMM). The preferential recognition of GMM antigen by MAP-infected cattle may be explained by the higher expression of GMM by MAP than by M. bovis. The bacterial species-specific nature of the CD1-restricted, adaptive T-cell response affects the approach to development of lipid based immunodiagnostic tests. PMID:19688747

Non-contiguous genome sequence of Mycobacterium simiae strain DSM 44165(T.).

PubMed

Sassi, Mohamed; Robert, Catherine; Raoult, Didier; Drancourt, Michel

2013-01-01

Mycobacterium simiae is a non-tuberculosis mycobacterium causing pulmonary infections in both immunocompetent and imunocompromized patients. We announce the draft genome sequence of M. simiae DSM 44165(T). The 5,782,968-bp long genome with 65.15% GC content (one chromosome, no plasmid) contains 5,727 open reading frames (33% with unknown function and 11 ORFs sizing more than 5000 -bp), three rRNA operons, 52 tRNA, one 66-bp tmRNA matching with tmRNA tags from Mycobacterium avium, Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium microti, Mycobacterium marinum, and Mycobacterium africanum and 389 DNA repetitive sequences. Comparing ORFs and size distribution between M. simiae and five other Mycobacterium species M. simiae clustered with M. abscessus and M. smegmatis. A 40-kb prophage was predicted in addition to two prophage-like elements, 7-kb and 18-kb in size, but no mycobacteriophage was seen after the observation of 10(6) M. simiae cells. Fifteen putative CRISPRs were found. Three genes were predicted to encode resistance to aminoglycosides, betalactams and macrolide-lincosamide-streptogramin B. A total of 163 CAZYmes were annotated. M. simiae contains ESX-1 to ESX-5 genes encoding for a type-VII secretion system. Availability of the genome sequence may help depict the unique properties of this environmental, opportunistic pathogen.

Diagnostic value of animal-side antibody assays for rapid detection of Mycobacterium bovis or Mycobacterium microti infection in South American camelids.

PubMed

Lyashchenko, Konstantin P; Greenwald, Rena; Esfandiari, Javan; Rhodes, Shelley; Dean, Gillian; de la Rua-Domenech, Ricardo; Meylan, Mireille; Vordermeier, H Martin; Zanolari, Patrik

2011-12-01

Tuberculosis (TB) in South American camelids (SAC) is caused by Mycobacterium bovis or Mycobacterium microti. Two serological methods, rapid testing (RT) and the dual-path platform (DPP) assay, were evaluated using naturally infected SAC. The study population included 156 alpacas and 175 llamas in Great Britain, Switzerland, and the United States. TB due to M. bovis (n = 44) or M. microti (n = 8) in 35 alpacas and 17 llamas was diagnosed by gross pathology examination and culture. Control animals were from herds with no TB history. The RT and the DPP assay showed sensitivities of 71% and 74%, respectively, for alpacas, while the sensitivity for llamas was 77% for both assays. The specificity of the DPP assay (98%) was higher than that of RT (94%) for llamas; the specificities of the two assays were identical (98%) for alpacas. When the two antibody tests were combined, the parallel-testing interpretation (applied when either assay produced a positive result) enhanced the sensitivities of antibody detection to 89% for alpacas and 88% for llamas but at the cost of lower specificities (97% and 93%, respectively), whereas the serial-testing interpretation (applied when both assays produced a positive result) maximized the specificity to 100% for both SAC species, although the sensitivities were 57% for alpacas and 65% for llamas. Over 95% of the animals with evidence of TB failed to produce skin test reactions, thus confirming concerns about the validity of this method for testing SAC. The findings suggest that serological assays may offer a more accurate and practical alternative for antemortem detection of camelid TB.

Protection against atypical Aeromonas salmonicida infection in carp (Cyprinus carpio L.) by oral administration of humus extract.

PubMed

Kodama, Hiroshi; Denso; Nakagawa, Tsuyoshi

2007-04-01

Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms have been present. In the present study, oral administration of humus extract to common carp (Cyprinus carpio L.) induced effective protection against experimental atypical Aeromonas salmonicida infection. Mortality of fish and development of skin lesions such as hemorrhages and ulcers were significantly suppressed in carp treated with 10%, 5% or 1% humus extract adsorbed on dry feeding pellets. The median surviving days was also greater in fish treated with 10% or 5% humus extract than in untreated fish. Atypical A. salmonicida was isolated from ulcerative lesions of part of dead fish, but Aeromonas hydrophila and Flavobacterium sp. were also isolated from these fish, verifying bacterial population changes during the progression of skin lesions. These results clearly show that treatment of fish with humus extract is effective in preventing A. salmonicida disease.

DIAGNOSIS AND IMPLICATIONS OF MYCOBACTERIUM BOVIS INFECTION IN BANDED MONGOOSES (MUNGOS MUNGO) IN THE KRUGER NATIONAL PARK, SOUTH AFRICA.

PubMed

Brüns, Angela C; Tanner, Manfred; Williams, Mark C; Botha, Louise; O'Brien, Amanda; Fosgate, Geoffrey T; van Helden, Paul D; Clarke, John; Michel, Anita L

2017-01-01

Bovine tuberculosis (bTB) was first diagnosed in the Kruger National Park (KNP) in 1990. Research has since focused on the maintenance host, the African buffalo ( Syncerus caffer ) and clinically affected lion ( Panthera leo ). However, little is known about the role of small predators in tuberculosis epidemiology. During 2011-12, we screened banded mongooses ( Mungos mungo ) in the bTB high-prevalence zone of the KNP for Mycobacterium tuberculosis complex members. Fecal swabs, tracheal swabs, and tracheal lavages of 76 banded mongooses caught in cage traps within a 2-km radius of Skukuza Rest Camp were submitted for Mycobacterium culture, isolation, and species identification. Lesions and lymph node samples collected from 12 animals at postmortem examination were submitted for culture and histopathology. In lung and lymph nodes of two banded mongooses, well demarcated, irregularly margined, gray-yellow nodules of up to 5 mm diameter were identified with either central necrosis or calcification, characterized on histopathology as caseating necrosis with epithelioid macrophages or necrogranuloma with calcified centre. No acid fast bacteria were identified with Ziehl-Neelsen stain. We isolated Mycobacterium bovis from lung, lymph node, and liver samples, as well as from tracheal lavages and tracheal swab from the same two banded mongooses. Blood samples were positive by ElephantTB STAT-PAK® Assay for 12 and Enferplex™ TB Assay for five animals. Only the two banded mongooses positive on pathology and M. bovis culture were positive on both serologic assays. We provide evidence of bTB infection in banded mongooses in the KNP, demonstrate their ability to shed M. bovis , and propose a possible antemortem diagnostic algorithm. Our findings open the discussion around possible sources of infection and their significance at the human/wildlife interface in and around Skukuza.

Seeing a Mycobacterium-Infected Cell in Nanoscale 3D: Correlative Imaging by Light Microscopy and FIB/SEM Tomography

PubMed Central

Beckwith, Marianne Sandvold; Beckwith, Kai Sandvold; Sikorski, Pawel; Skogaker, Nan Tostrup

2015-01-01

Mycobacteria pose a threat to the world health today, with pathogenic and opportunistic bacteria causing tuberculosis and non-tuberculous disease in large parts of the population. Much is still unknown about the interplay between bacteria and host during infection and disease, and more research is needed to meet the challenge of drug resistance and inefficient vaccines. This work establishes a reliable and reproducible method for performing correlative imaging of human macrophages infected with mycobacteria at an ultra-high resolution and in 3D. Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) tomography is applied, together with confocal fluorescence microscopy for localization of appropriately infected cells. The method is based on an Aclar poly(chloro-tri-fluoro)ethylene substrate, micropatterned into an advantageous geometry by a simple thermomoulding process. The platform increases the throughput and quality of FIB/SEM tomography analyses, and was successfully applied to detail the intracellular environment of a whole mycobacterium-infected macrophage in 3D. PMID:26406896

Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells.

PubMed

Rivas-Santiago, Bruno; Hernandez-Pando, Rogelio; Carranza, Claudia; Juarez, Esmeralda; Contreras, Juan Leon; Aguilar-Leon, Diana; Torres, Martha; Sada, Eduardo

2008-03-01

The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.

Three Mycobacterium tuberculosis Rel Toxin-Antitoxin Modules Inhibit Mycobacterial Growth and Are Expressed in Infected Human Macrophages▿

PubMed Central

Korch, Shaleen B.; Contreras, Heidi; Clark-Curtiss, Josephine E.

2009-01-01

Mycobacterium tuberculosis protein pairs Rv1246c-Rv1247c, Rv2865-Rv2866, and Rv3357-Rv3358, here named RelBE, RelFG, and RelJK, respectively, were identified based on homology to the Escherichia coli RelBE toxin:antitoxin (TA) module. In this study, we have characterized each Rel protein pair and have established that they are functional TA modules. Overexpression of individual M. tuberculosis rel toxin genes relE, relG, and relK induced growth arrest in Mycobacterium smegmatis; a phenotype that was completely reversible by expression of their cognate antitoxin genes, relB, relF, and relJ, respectively. We also provide evidence that RelB and RelE interact directly, both in vitro and in vivo. Analysis of the genetic organization and regulation established that relBE, relFG, and relJK form bicistronic operons that are cotranscribed and autoregulated, in a manner unlike typical TA modules. RelB and RelF act as transcriptional activators, inducing expression of their respective promoters. However, RelBE, RelFG, and RelJK (together) repress expression to basal levels of activity, while RelJ represses promoter activity altogether. Finally, we have determined that all six rel genes are expressed in broth-grown M. tuberculosis, whereas relE, relF, and relK are expressed during infection of human macrophages. This is the first demonstration of M. tuberculosis expressing TA modules in broth culture and during infection of human macrophages. PMID:19114484

Observed management practices in relation to the risk of infection with paratuberculosis and to the spread of Mycobacterium avium subsp. paratuberculosis in Swiss dairy and beef herds

PubMed Central

2014-01-01

Background Many studies have been conducted to define risk factors for the transmission of bovine paratuberculosis, mostly in countries with large herds. Little is known about the epidemiology in infected Swiss herds and risk factors important for transmission in smaller herds. Therefore, the presence of known factors which might favor the spread of paratuberculosis and could be related to the prevalence at animal level of fecal shedding of Mycobacterium avium subsp. paratuberculosis were assessed in 17 infected herds (10 dairy, 7 beef). Additionally, the level of knowledge of herd managers about the disease was assessed. In a case–control study with 4 matched negative control herds per infected herd, the association of potential risk factors with the infection status of the herd was investigated. Results Exposure of the young stock to feces of older animals was frequently observed in infected and in control herds. The farmers’ knowledge about paratuberculosis was very limited, even in infected herds. An overall prevalence at animal level of fecal shedding of Mycobacterium avium subsp. paratuberculosis of 6.1% was found in infected herds, whereby shedders younger than 2 years of age were found in 46.2% of the herds where the young stock was available for testing. Several factors related to contamination of the heifer area with cows’ feces and the management of the calving area were found to be significantly associated with the within-herd prevalence. Animal purchase was associated with a positive herd infection status (OR = 7.25, p = 0.004). Conclusions Numerous risk factors favoring the spread of Mycobacterium avium subsp. paratuberculosis from adult animals to the young stock were observed in infected Swiss dairy and beef herds, which may be amenable to improvement in order to control the disease. Important factors were contamination of the heifer and the calving area, which were associated with higher within-herd prevalence of fecal shedding. The

Mycobacterium marinum infection in a blue-fronted Amazon parrot (Amazona aestiva).

PubMed

Hannon, David E; Bemis, David A; Garner, Michael M

2012-12-01

A blue-fronted Amazon parrot (Amazona aestiva) was presented with a granuloma involving the proximal rhinotheca and extending into the rostral sinuses. Mycobacterium marinum was diagnosed based on results of biopsy and culture. Treatment was initiated with clarithromycin, rifampin, and ethambutol, but the bird died 4 months after the onset of antimicrobial therapy. Additional granulomas were found in the left lung and liver on postmortem examination. Mycobacterial isolation on postmortem samples was unsuccessful. This is the first report of Mycobacterium marinum in a bird.

Effect of Mycobacterium paratuberculosis infection on production, reproduction, and health traits in US Holsteins.

PubMed

Gonda, M G; Chang, Y M; Shook, G E; Collins, M T; Kirkpatrick, B W

2007-07-16

Our objective was to estimate the effect of Mycobacterium paratuberculosis infection on milk, fat, and protein yield deviations, pregnancy rate, lactation somatic cell score, and projected total months in milk (productive life). A serum ELISA and fecal culture for M. paratuberculosis were performed on 4375 Holsteins in 232 DHIA herds throughout the US. Primarily first through third lactation cows (99% of total) were assayed for infection. Trait information (except productive life) was obtained for the lactation concurrent with disease tests. Productive life was total months in milk through a cow's life, which was projected if a cow was still milking. For most analyses, case definition for M. paratuberculosis infection was defined as either an ELISA S/P ratio>or=0.25 or a positive fecal culture for M. paratuberculosis or both. To determine if diagnostic test affected estimates, case definition was redefined to include only cows with ELISA S/P ratios>or=0.25 or only fecal culture-positive cows. Linear models were used to estimate effect of M. paratuberculosis infection on traits. M. paratuberculosis-infected cows (7.89% of cows) produced 303.9 kg less milk/lactation, 11.46 kg less fat/lactation, and 9.49 kg less protein/lactation (PInfected cows had higher pregnancy rates (1.39%) (P=0.0385) and lower productive life (2.85 months) (Pinfection did not affect somatic cell score. Effect of infection on milk and protein yields was larger in first lactation M. paratuberculosis-positive cows relative to cows that tested positive in later lactations. Fecal culture-positive cows had consistently larger effects on all traits than ELISA-positive cows. M. paratuberculosis infection, and not just clinical Johne's disease, decreases milk, fat, and protein yields, thus increasing the estimated cost of paratuberculosis to the US dairy industry.

Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice.

PubMed

Monin, Leticia; Mehta, Shail; Elsegeiny, Waleed; Gopal, Radha; McAleer, Jeremy P; Oury, Tim D; Kolls, Jay; Khader, Shabaana A

2018-03-01

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus -coinfected lungs. Our results demonstrate that A. fumigatus , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model. Copyright © 2018 American Society for Microbiology.

Infection caused by Mycobacterium tuberculosis.

PubMed

Peloquin, C A; Berning, S E

1994-01-01

To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future. The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts. Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis. Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented. The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug-resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control

Severe Disseminated Mycobacterium avium Infection in a Patient with a Positive Serum Autoantibody to Interferon-γ

PubMed Central

Ikeda, Hiroshi; Nakamura, Kiwamu; Ikenori, Mei; Saito, Takahiro; Nagamine, Keisuke; Inoue, Minoru; Sakagami, Takuro; Suzuki, Hiroko; Usui, Mariko; Kanemitsu, Keiji; Matsumoto, Akinori; Shinbo, Takuro

2016-01-01

We herein report a case of disseminated Mycobacterium avium infection that involved both optic nerves, the conjunctiva, the right lower lung, and multiple skin lesions, including a thoracic nodule. The patient was a 65-year-old man without any significant medical history. The pathogen was detected in the patient's eye discharge, sputum, bronchial lavage fluid, and thoracic nodule. Anti-mycobacterial chemotherapy, including clarithromycin, rifampicin, and ethambutol, was administered, and the thoracic nodule was resected. An autoantibody to interferon-γ was detected in the patient's serum. Bilateral swelling of his optic nerves and facial dermatitis improved after initiating anti-mycobacterial chemotherapy. PMID:27746449

Bilateral Mycobacterium chelonae Keratitis after Phacoemulsification Cataract Surgery.

PubMed

Martinez, Jaime D; Amescua, Guillermo; Lozano-Cárdenas, Jesus; Suh, Leejee H

2017-01-01

The purpose of this manuscript is to report the case of an 81-year-old patient who presented with bilateral keratitis after phacoemulsification surgery. Cultures came back positive for Mycobacterium chelonae . Despite aggressive topical and systemic antimicrobial treatment, the patient developed a corneal perforation in both eyes, treated with corneal glue in the right eye and corneoscleral patch in the left eye. After two years of follow-up, patient was free of infection in the right eye with visual acuity of 20/200 and the left eye progressed to phthisis bulbi. We present an unusual case of bilateral Mycobacterium chelonae keratitis associated with phacoemulsification cataract surgery. This case represents the importance of making clinicians aware of this devastating infection and highlights the need for better management to improve outcomes.

Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1.

PubMed

McElvania Tekippe, Erin; Allen, Irving C; Hulseberg, Paul D; Sullivan, Jonathan T; McCann, Jessica R; Sandor, Matyas; Braunstein, Miriam; Ting, Jenny P-Y

2010-08-20

The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1beta secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3(-/-), Casp-1(-/-), and WT mice showed no differences in pulmonary IL-1beta production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard(-/-) mice. Decreased survival of Pycard(-/-) animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.

First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance

PubMed Central

2010-01-01

Background The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in katG, rpoB and inhA genes, resulting in isoniazid (INH) and rifampin (RIF) resistance. Results Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as M. bovis, 9 as M. avium and 1 as M. intracellulare. IS6110-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 M. bovis strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG → TCG (Glu → Ser) at codon 469 of rpoB gene. Conclusions This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control. PMID:20236539

Differential Transcriptional Response in Macrophages Infected with Cell Wall Deficient versus Normal Mycobacterium Tuberculosis

PubMed Central

Fu, Yu-Rong; Gao, Kun-Shan; Ji, Rui; Yi, Zheng-Jun

2015-01-01

Host-pathogen interactions determine the outcome following infection by mycobacterium tuberculosis (Mtb). Under adverse circumstances, normal Mtb can form cell-wall deficient (CWD) variants within macrophages, which have been considered an adaptive strategy for facilitating bacterial survival inside macrophages. However, the molecular mechanism by which infection of macrophages with different phenotypic Mtb elicits distinct responses of macrophages is not fully understood. To explore the molecular events triggered upon Mtb infection of macrophages, differential transcriptional responses of RAW264.7 cells infected with two forms of Mtb, CWD-Mtb and normal Mtb, were studied by microarray analysis. Some of the differentially regulated genes were confirmed by RT-qPCR in both RAW264.7 cells and primary macrophages. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was used to analyze functions of differentially expressed genes. Distinct gene expression patterns were observed between CWD-Mtb and normal Mtb group. Mapt was up-regulated, while NOS2 and IL-11 were down-regulated in CWD-Mtb infected RAW264.7 cells and primary macrophages compared with normal Mtb infected ones. Many deregulated genes were found to be related to macrophages activation, immune response, phagosome maturation, autophagy and lipid metabolism. KEGG analysis showed that the differentially expressed genes were mainly involved in MAPK signaling pathway, nitrogen metabolism, cytokine-cytokine receptor interaction and focal adhesion. Taken together, the present study showed that differential macrophage responses were induced by intracellular CWD-Mtb an normal Mtb infection, which suggested that interactions between macrophages and different phenotypic Mtb are very complex. The results provide evidence for further understanding of pathogenesis of CWD-Mtb and may help in improving strategies to eliminate intracellular CWD-Mtb. PMID:25552926

Airborne Mycobacterium avium infection in a group of red-shanked douc langurs (Pygathrix nemaeus nemaeus).

PubMed

Plesker, Roland; Teschner, Katja; Behlert, Olaf; Prenger-Berninghoff, Ellen; Hillemann, Doris

2010-04-01

This report describes an airborne Mycobacterium avium (MA)-infection in two red-shanked douc langurs (Pygathrix nemaeus nemaeus) from Cologne zoo. The two individuals and their tissues were investigated clinically (including x-rays), in pathology, in pathohistology, in classical bacteriology and by polymerase chain reaction (PCR). Clinically, one individual displayed emaciation and a positive reaction in an intrapalpebral testing for M. bovis/MA. The other individual was without any symptoms and did not show any reaction in the intrapalpebral test. In x-ray photos of the lungs, calcified nodules were detected. In pathology, calcified and necrotic nodules were observed within the lungs and the bronchial lymph nodes. In pathohistology, both classical tuberculous granulomas, and few acid fast rods were seen in Ziehl-Neelsen-stain. However, classical bacteriology could not demonstrate mycobacteria. In PCR, MA-infection could be confirmed in one individual using the bronchial lymph nodes. It was an airborne infection; however, the definite source of infection in these cases remained unclear. Animals in contact to the langurs (house sparrows and mice) as well as water used in the building are the most promising candidates. The risk for a zoonotic transmission in these cases has been calculated to be low.

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

PubMed Central

2015-01-01

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. PMID:26064970

Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

PubMed

Ufimtseva, Elena

2015-01-01

Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

Low dose aerosol fitness at the innate phase of murine infection better predicts virulence amongst clinical strains of Mycobacterium tuberculosis.

PubMed

Caceres, Neus; Llopis, Isaac; Marzo, Elena; Prats, Clara; Vilaplana, Cristina; de Viedma, Dario Garcia; Samper, Sofía; Lopez, Daniel; Cardona, Pere-Joan

2012-01-01

Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 10⁴ CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 10² CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism of the induction of active TB derived from the dynamic hypothesis of latent tuberculosis infection.

To achieve an earlier IFN-γ response is not sufficient to control Mycobacterium tuberculosis infection in mice.

PubMed

Vilaplana, Cristina; Prats, Clara; Marzo, Elena; Barril, Carles; Vegué, Marina; Diaz, Jorge; Valls, Joaquim; López, Daniel; Cardona, Pere-Joan

2014-01-01

The temporo-spatial relationship between the three organs (lung, spleen and lymph node) involved during the initial stages of Mycobacterium tuberculosis infection has been poorly studied. As such, we performed an experimental study to evaluate the bacillary load in each organ after aerosol or intravenous infection and developed a mathematical approach using the data obtained in order to extract conclusions. The results showed that higher bacillary doses result in an earlier IFN-γ response, that a certain bacillary load (BL) needs to be reached to trigger the IFN-γ response, and that control of the BL is not immediate after onset of the IFN-γ response, which might be a consequence of the spatial dimension. This study may have an important impact when it comes to designing new vaccine candidates as it suggests that triggering an earlier IFN-γ response might not guarantee good infection control, and therefore that additional properties should be considered for these candidates.

To Achieve an Earlier IFN-γ Response Is Not Sufficient to Control Mycobacterium tuberculosis Infection in Mice

PubMed Central

Marzo, Elena; Barril, Carles; Vegué, Marina; Diaz, Jorge; Valls, Joaquim; López, Daniel; Cardona, Pere-Joan

2014-01-01

The temporo-spatial relationship between the three organs (lung, spleen and lymph node) involved during the initial stages of Mycobacterium tuberculosis infection has been poorly studied. As such, we performed an experimental study to evaluate the bacillary load in each organ after aerosol or intravenous infection and developed a mathematical approach using the data obtained in order to extract conclusions. The results showed that higher bacillary doses result in an earlier IFN-γ response, that a certain bacillary load (BL) needs to be reached to trigger the IFN-γ response, and that control of the BL is not immediate after onset of the IFN-γ response, which might be a consequence of the spatial dimension. This study may have an important impact when it comes to designing new vaccine candidates as it suggests that triggering an earlier IFN-γ response might not guarantee good infection control, and therefore that additional properties should be considered for these candidates. PMID:24959669

Skin test performed with highly purified Mycobacterium tuberculosis recombinant protein triggers tuberculin shock in infected guinea pigs.

PubMed

Reece, Stephen T; Stride, Nicole; Ovendale, Pamela; Reed, Steven G; Campos-Neto, Antonio

2005-06-01

Tuberculin shock due to inoculation of Mycobacterium tuberculosis antigens in patients with tuberculosis is a serious syndrome originally described over 100 years ago by Robert Koch. Here, we present experimental evidence that a single M. tuberculosis recombinant protein, CFP-10, triggers this syndrome. Intradermal inoculation of CFP-10 elicits in M. tuberculosis-infected mice high levels of serum tumor necrosis factor alpha and causes tuberculin shock in infected guinea pigs characterized by hypothermia and death within 6 to 48 h after the antigen inoculation. Autopsies of these animals revealed intense polycythemia and hemorrhagic patches in the lung parenchyma, a pathological observation consistent with tuberculin shock. These results point to the possible occurrence of tuberculin shock in sensitive individuals inoculated with highly purified M. tuberculosis recombinant proteins as vaccine candidates or skin test reagents.

Revisiting Host Preference in the Mycobacterium tuberculosis Complex: Experimental Infection Shows M. tuberculosis H37Rv to Be Avirulent in Cattle

PubMed Central

Whelan, Adam O.; Coad, Michael; Cockle, Paul J.; Hewinson, Glyn; Vordermeier, Martin; Gordon, Stephen V.

2010-01-01

Experiments in the late 19th century sought to define the host specificity of the causative agents of tuberculosis in mammals. Mycobacterium tuberculosis, the human tubercle bacillus, was independently shown by Smith, Koch, and von Behring to be avirulent in cattle. This finding was erroneously used by Koch to argue the converse, namely that Mycobacterium bovis, the agent of bovine tuberculosis, was avirulent for man, a view that was subsequently discredited. However, reports in the literature of M. tuberculosis isolation from cattle with tuberculoid lesions suggests that the virulence of M. tuberculosis for cattle needs to be readdressed. We used an experimental bovine infection model to test the virulence of well-characterized strains of M. tuberculosis and M. bovis in cattle, choosing the genome-sequenced strains M. tuberculosis H37Rv and M. bovis 2122/97. Cattle were infected with approximately 106 CFU of M. tuberculosis H37Rv or M. bovis 2122/97, and sacrificed 17 weeks post-infection. IFN-γ and tuberculin skin tests indicated that both M. bovis 2122 and M. tuberculosis H37Rv were equally infective and triggered strong cell-mediated immune responses, albeit with some indication of differential antigen-specific responses. Postmortem examination revealed that while M. bovis 2122/97–infected animals all showed clear pathology indicative of bovine tuberculosis, the M. tuberculosis–infected animals showed no pathology. Culturing of infected tissues revealed that M. tuberculosis was able to persist in the majority of animals, albeit at relatively low bacillary loads. In revisiting the early work on host preference across the M. tuberculosis complex, we have shown M. tuberculosis H37Rv is avirulent for cattle, and propose that the immune status of the animal, or genotype of the infecting bacillus, may have significant bearing on the virulence of a strain for cattle. This work will serve as a baseline for future studies into the genetic basis of host preference

Pulmonary Mycobacterium kansasii infection: comparison of the clinical features, treatment and outcome with pulmonary tuberculosis.

PubMed Central

Evans, S. A.; Colville, A.; Evans, A. J.; Crisp, A. J.; Johnston, I. D.

1996-01-01

BACKGROUND: In the United Kingdom Mycobacterium kansasii is the most common pulmonary non-tuberculous mycobacteria to cause disease in the non-HIV positive population. METHODS: The clinical features, treatment, and outcome of 47 patients (13 women) of mean (SD) age 58 (17) years with culture positive pulmonary M kansasii infection were compared with those of 87 patients (23 women) of mean (SD) age 57 (16) years with culture positive pulmonary M tuberculosis infection by review of their clinical and laboratory records. Each patient with M kansasii infection was matched for age, sex, race and, where possible, year of diagnosis with two patients with M tuberculosis infection. RESULTS: All those with M kansasii infection were of white race. Haemoptysis was more common in patients infected with M kansasii but they were less likely to present as a result of an incidental chest radiograph or symptoms other than those due to mycobacterial infection. Patients with M kansasii were also less likely to have a history of diabetes, but the frequency of previous chest disease and tuberculosis was similar. An alcohol intake of > 14 units/week was less frequent in those with M kansasii, but there were no significant differences in drug history, past and present smoking habit, occupational exposures, social class, or marital status. Patients with M kansasii received a longer total course of antimycobacterial therapy and, in particular, extended treatment with ethambutol and rifampicin was given. There was no significant difference in outcome between pulmonary M kansasii or M tuberculosis infection. CONCLUSIONS: There are group differences between the clinical features of the two infections but, with the possible exception of diabetes and alcohol intake, these features are unlikely to be diagnostically helpful. Treatment of M kansasii infection with ethambutol, isoniazid, and rifampicin in these patients was as effective as standard regimens given to patients infected with M

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Dietrich, Jes; Tan, Esterlina; Abalos, Rodolfo M.; Burgos, Jasmin; Bigbee, Carolyn; Bigbee, Matthew; Milk, Leslie; Gideon, Hannah P.; Rodgers, Mark; Cochran, Catherine; Guinn, Kristi M.; Sherman, David R.; Klein, Edwin; Janssen, Christopher; Flynn, JoAnne L.; Andersen, Peter

2011-01-01

It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress–induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56. PMID:22133873

Kinetics of the immune response profile in guinea pigs after vaccination with Mycobacterium bovis BCG and infection with Mycobacterium tuberculosis.

PubMed

Grover, Ajay; Taylor, Jennifer; Troudt, JoLynn; Keyser, Andrew; Arnett, Kimberly; Izzo, Linda; Rholl, Drew; Izzo, Angelo

2009-11-01

The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-gamma) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+ CD62Llow and CD8+ CD62Llow) and mRNA expression of IFN-gamma, tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-gamma mRNA expression but decreased TNF-alpha mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-gamma mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+ CD62Llow T cells at day 40, although the numbers of CD8+ CD62Llow T cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection.

Prevalence of small ruminant lentivirus and Mycobacterium avium subsp. paratuberculosis co-infection in Ontario dairy sheep and dairy goats.

PubMed

Stonos, Nancy; Bauman, Cathy; Menzies, Paula; Wootton, Sarah K; Karrow, Niel A

2017-04-01

Infection with small ruminant lentiviruses (SRLV) causes a variety of chronic inflammatory conditions that limit production. Mycobacterium avium subsp. paratuberculosis (MAP) is also a major production-limiting disease of sheep and goats, which causes severe inflammation of the small intestine. Previous studies have indicated that both SRLV and MAP are widespread in small ruminants in Ontario. This study estimated the prevalence of SRLV and MAP co-infection. Serum samples that were previously tested for MAP infection were re-tested for SRLV. The apparent prevalence of co-infection was low, with 3.4% [95% confidence interval (CI): 1.9 to 5.9] and 14.3% (95% CI: 11.6 to 17.5) of sheep and goats respectively, positive for both infections. However, co-infection is widespread with 36.8% (95% CI: 19.1 to 59.1) and 71.4% (95% CI: 52.8 to 84.9) of sheep and goat farms with 1 or more co-infected animals. A significant association was found between SRLV seropositivity and MAP fecal culture ( P = 0.021), suggesting that co-infected goats may be more likely to shed MAP in their feces.

Effects of helminths and Mycobacterium tuberculosis infection on HIV-1: a cellular immunological perspective.

PubMed

Mouser, Emily E I M; Pollakis, Georgios; Paxton, William A

2012-05-01

In many regions of the world, a high prevalence of HIV-1, helminthic and Mycobacterium tuberculosis (Mtb) infections can be found. Here, we summarize the types of immune responses induced and/or modulated by these pathogens and the consequences for HIV-1 disease. Helminths predominantly induce strong T helper (Th) 2 cellular responses which are downregulated in chronic disease. The anatomical niche populated by helminths plays a key factor in the effect these parasites have on HIV-1 transmission and subsequent replication. Gut-associated helminths have been found to increase HIV-1 transmission via the lesions they provide. In spite of this, the many immune modulatory molecules secreted by the parasites may inhibit or slow HIV-1 infection. In contrast, Mtb is mainly restricted to the lung and the Mtb-specific Th cells induced are highly susceptible to HIV-1 infection and replication. Antigens from both pathogens have immunomodulatory activity that can skew cellular immune responses in specific directions. The effect of helminths and Mtb on modulating immune responses is varied and complex with both their location and phenotype potentially influencing HIV-1 disease. These pathogens have evolved a complex array of molecules which have the capacity to modulate immunity and preserve pathogen survival.

Herpes zoster - typical and atypical presentations.

PubMed

Dayan, Roy Rafael; Peleg, Roni

2017-08-01

Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

An investigation on the population structure of mixed infections of Mycobacterium tuberculosis in Inner Mongolia, China.

PubMed

Wang, Xiaoying; Liu, Haican; Wei, Jianhao; Wu, Xiaocui; Yu, Qin; Zhao, Xiuqin; Lyu, Jianxin; Lou, Yongliang; Wan, Kanglin

2015-12-01

Mixed infections of Mycobacterium tuberculosis strains have attracted more attention due to their increasing frequencies worldwide, especially in the areas of high tuberculosis (TB) prevalence. In this study, we accessed the rates of mixed infections in a setting with high TB prevalence in Inner Mongolia Autonomous Region of China. A total of 384 M. tuberculosis isolates from the local TB hospital were subjected to mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing method. The single clones of the strains with mixed infections were separated by subculturing them on the Löwenstein-Jensen medium. Of these 384 isolates, twelve strains (3.13%) were identified as mixed infections by MIRU-VNTR. Statistical analysis indicated that demographic characteristics and drug susceptibility profiles showed no statistically significant association with the mixed infections. We further subcultured the mixed infection strains and selected 30 clones from the subculture for each mixed infection. Genotyping data revealed that eight (8/12, 66.7%) strains with mixed infections had converted into single infection through subculture. The higher growth rate was associated with the increasing proportion of variant subpopulation through subculture. In conclusion, by using the MIRU-VNTR method, we demonstrate that the prevalence of mixed infections in Inner Mongolia is low. Additionally, our findings reveal that the subculture changes the population structures of mixed infections, and the subpopulation with higher growth rate show better fitness, which is associated with high proportion among the population structure after subculture. This study highlights that the use of clinical specimens, rather than subcultured isolates, is preferred to estimate the prevalence of mixed infections in the specific regions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differences between Mycobacterium-Host Cell Relationships in Latent Tuberculous Infection of Mice Ex Vivo and Mycobacterial Infection of Mouse Cells In Vitro

PubMed Central

Ufimtseva, Elena

2016-01-01

The search for factors that account for the reproduction and survival of mycobacteria, including vaccine strains, in host cells is the priority for studies on tuberculosis. A comparison of BCG-mycobacterial loads in granuloma cells obtained from bone marrow and spleens of mice with latent tuberculous infection and cells from mouse bone marrow and peritoneal macrophage cultures infected with the BCG vaccine in vitro has demonstrated that granuloma macrophages each normally contained a single BCG-Mycobacterium, while those acutely infected in vitro had increased mycobacterial loads and death rates. Mouse granuloma cells were observed to produce the IFNγ, IL-1α, GM-CSF, CD1d, CD25, CD31, СD35, and S100 proteins. None of these activation markers were found in mouse cell cultures infected in vitro or in intact macrophages. Lack of colocalization of lipoarabinomannan-labeled BCG-mycobacteria with the lysosomotropic LysoTracker dye in activated granuloma macrophages suggests that these macrophages were unable to destroy BCG-mycobacteria. However, activated mouse granuloma macrophages could control mycobacterial reproduction in cells both in vivo and in ex vivo culture. By contrast, a considerable increase in the number of BCG-mycobacteria was observed in mouse bone marrow and peritoneal macrophages after BCG infection in vitro, when no expression of the activation-related molecules was detected in these cells. PMID:27066505

Diagnostic Value of Animal-Side Antibody Assays for Rapid Detection of Mycobacterium bovis or Mycobacterium microti Infection in South American Camelids▿

PubMed Central

Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Rhodes, Shelley; Dean, Gillian; de la Rua-Domenech, Ricardo; Meylan, Mireille; Vordermeier, HMartin; Zanolari, Patrik

2011-01-01

Tuberculosis (TB) in South American camelids (SAC) is caused by Mycobacterium bovis or Mycobacterium microti. Two serological methods, rapid testing (RT) and the dual-path platform (DPP) assay, were evaluated using naturally infected SAC. The study population included 156 alpacas and 175 llamas in Great Britain, Switzerland, and the United States. TB due to M. bovis (n = 44) or M. microti (n = 8) in 35 alpacas and 17 llamas was diagnosed by gross pathology examination and culture. Control animals were from herds with no TB history. The RT and the DPP assay showed sensitivities of 71% and 74%, respectively, for alpacas, while the sensitivity for llamas was 77% for both assays. The specificity of the DPP assay (98%) was higher than that of RT (94%) for llamas; the specificities of the two assays were identical (98%) for alpacas. When the two antibody tests were combined, the parallel-testing interpretation (applied when either assay produced a positive result) enhanced the sensitivities of antibody detection to 89% for alpacas and 88% for llamas but at the cost of lower specificities (97% and 93%, respectively), whereas the serial-testing interpretation (applied when both assays produced a positive result) maximized the specificity to 100% for both SAC species, although the sensitivities were 57% for alpacas and 65% for llamas. Over 95% of the animals with evidence of TB failed to produce skin test reactions, thus confirming concerns about the validity of this method for testing SAC. The findings suggest that serological assays may offer a more accurate and practical alternative for antemortem detection of camelid TB. PMID:22012976

Intradermal tuberculin testing of wild African lions (Panthera leo) naturally exposed to infection with Mycobacterium bovis.

PubMed

Keet, D F; Michel, A L; Bengis, R G; Becker, P; van Dyk, D S; van Vuuren, M; Rutten, V P M G; Penzhorn, B L

2010-08-26

African lions in the southern half of Kruger National Park (KNP) are infected with Mycobacterium bovis. Historically, reliable detection of mycobacteriosis in lions was limited to necropsy and microbiological analysis of lesion material collected from emaciated and ailing or repeat-offender lions. We report on a method of cervical intradermal tuberculin testing of lions and its interpretation capable of identifying natural exposure to M. bovis. Infected lions (n=52/95) were identified by detailed necropsy and mycobacterial culture. A large proportion of these confirmed infected lions (45/52) showed distinct responses to bovine tuberculin purified protein derivative (PPD) while responses to avian tuberculin PPD were variable and smaller. Confirmed uninfected lions from non-infected areas (n=11) responded variably to avian tuberculin PPD only. Various non-tuberculous mycobacteria (NTM) were cultured from 45/95 lions examined, of which 21/45 were co-infected with M. bovis. Co-infection with M. bovis and NTM did not influence skin reactions to bovine tuberculin PPD. Avian tuberculin PPD skin reactions were larger in M. bovis-infected lions compared to uninfected ones. Since NTM co-infections are likely to influence the outcome of skin testing, stricter test interpretation criteria were applied. When test data of bovine tuberculin PPD tests were considered on their own, as for a single skin test, sensitivity increased (80.8-86.5%) but false positive rate for true negatives (18.75%) remained unchanged. Finally, the adapted skin test procedure was shown not to be impeded by persistent Feline Immunodeficiency Virus(Ple) co-infection. Copyright 2010 Elsevier B.V. All rights reserved.

Chronic Mycobacterium infection of first dorsal web space after accidental Bacilli Calmette-Guérin injection in a health worker: case report.

PubMed

Vigler, Mordechai; Mulett, Hanan; Hausman, Michael R

2008-11-01

We present a case of inoculation of the first dorsal web space by a nurse practitioner who accidentally stuck herself while preparing Bacilli Calmette-Guérin vaccine for treatment of bladder tumor. We report the evolution and management of this resistant chronic Mycobacterium infection that ultimately required use of a vacuum wound management system followed by a microvascular free tissue transfer.

Conflicting Role of Mycobacterium Species in Multiple Sclerosis

PubMed Central

Cossu, Davide; Yokoyama, Kazumasa; Hattori, Nobutaka

2017-01-01

Mycobacterium is a genus of aerobic and acid-fast bacteria, which include several pathogenic organisms that cause serious diseases in mammals. Previous studies have associated the immune response against mycobacteria with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system with unknown etiology. The role of mycobacteria in the pathological process has been controversial and often conflicting. We provide a detailed review of the mycobacteria that have been linked to MS over the last three decades, with a focus on Mycobacterium bovis bacille Calmette–Guérin vaccine for human and oral exposure to Mycobacterium avium subsp. paratuberculosis. We will also discuss the exposure and genetic susceptibility to mycobacterial infection, the protective role of vaccination, as well as the possible mechanisms involved in initiating or worsening MS symptoms, with particular emphasis on the molecular mimicry between mycobacterial and human proteins. Finally, we will introduce topics such as heat shock proteins and recognition by innate immunity, and toll-like receptor signaling-mediated responses to Mycobacterium exposure. PMID:28579973

HIV infection impairs Th1 and Th17 Mycobacterium tuberculosis-specific T cell responses

PubMed Central

Murray, Lyle W; Satti, Iman; Meyerowitz, Jodi; Jones, Matthew; Willberg, Christian B; Ussher, James E; Goedhals, Dominique; Hurst, Jacob; Phillips, Rodney E; McShane, Helen

2018-01-01

Background HIV-infected individuals have a higher risk of developing active tuberculosis than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (M.tb)-specific CD4+ and CD8+ T cell responses contributed to this increased risk. Methods M.tb-specific T cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa were evaluated. Using a whole-blood flow cytometry assay, we measured expression of IFNγ, TNFα, IL-2 and IL-17 in CD4+ and CD8+ T cells in response to M.tb antigens (PPD, ESAT-6/CFP-10 (EC) and DosR regulon-encoded α-crystallin (Rv2031c)). Results Fewer HIV-infected individuals had detectable CD4+ and CD8+ T cell responses to PPD and Rv2031c than HIV-uninfected subjects. M.tb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions HIV-associated impairment of CD4+ and CD8+ M.tb-specific T cell responses is antigen-specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T cell subset may be key to TB susceptibility in HIV-infected individuals. PMID:29546381

Necroptotic signaling is primed in Mycobacterium tuberculosis-infected macrophages, but its pathophysiological consequence in disease is restricted.

PubMed

Stutz, Michael D; Ojaimi, Samar; Allison, Cody; Preston, Simon; Arandjelovic, Philip; Hildebrand, Joanne M; Sandow, Jarrod J; Webb, Andrew I; Silke, John; Alexander, Warren S; Pellegrini, Marc

2018-05-01

Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu. However, blocking necroptosis either by deleting Mlkl or inhibiting RIPK1 had no effect on the survival of infected human or murine macrophages. Consistent with this, MLKL-deficiency or treatment of humanized mice with the RIPK1 inhibitor Nec-1s did not impact on disease outcomes in vivo, with mice displaying lung histopathology and bacterial burdens indistinguishable from controls. Therefore, although the necroptotic pathway is primed by Mtb infection, macrophage necroptosis is ultimately restricted to mitigate disease pathogenesis. We identified cFLIP upregulation that may promote caspase 8-mediated degradation of CYLD, and other necrosome components, as a possible mechanism abrogating Mtb's capacity to coopt necroptotic signaling. Variability in the capacity of these mechanisms to interfere with necroptosis may influence disease severity and could explain the heterogeneity of Mtb infection and disease.

Risk factors for Mycobacterium tuberculosis infection in 2-4 year olds in a rural HIV-prevalent setting.

PubMed

Khan, P Y; Glynn, J R; Fielding, K L; Mzembe, T; Mulawa, D; Chiumya, R; Fine, P E M; Koole, O; Kranzer, K; Crampin, A C

2016-03-01

Mycobacterium tuberculosis infection in children acts as a sentinel for infectious tuberculosis. To assess risk factors associated with tuberculous infection in pre-school children. We conducted a population-wide tuberculin skin test (TST) survey from January to December 2012 in Malawi. All children aged 2-4 years residing in a demographic surveillance area were eligible. Detailed demographic data, including adult human immunodeficiency virus (HIV) status, and clinical and sociodemographic data on all diagnosed tuberculosis (TB) patients were available. The prevalence of M. tuberculosis infection was 1.1% using a TST induration cut-off of 15 mm (estimated annual risk of infection of 0.3%). The main identifiable risk factors were maternal HIV infection at birth (adjusted OR [aOR] 3.6, 95%CI 1.1-12.2), having three or more adult members in the household over a lifetime (aOR 2.4, 95%CI 1.2-4.8) and living in close proximity to a known case of infectious TB (aOR 1.6, 95%CI 1.1-2.4), modelled as a linear variable across categories (>200 m, 100-200 m, <100 m, within household). Less than 20% of the infected children lived within 200 m of a known diagnosed case. Household and community risk factors identified do not explain the majority of M. tuberculosis infections in children in our setting.

Evolution of Mycobacterium tuberculosis.

PubMed

Behr, Marcel A

2013-01-01

Genomic studies have provided a refined understanding of the genetic diversity within the Mycobacterium genus, and more specifically within Mycobacterium tuberculosis. These results have informed a new perspective on the macro- and micro-evolution of the tubercle bacillus. In the first step, a M. kansasii-like opportunistic pathogen acquired new genes, through horizontal gene transfer, that enabled it to better exploit an intracellular niche and ultimately evolve into a professional pathogen. In the second step, different subspecies and strains of the M. tuberculosis complex emerged through mutation and deletion of unnecessary DNA. Understanding the differences between M. tuberculosis and related less pathogenic mycobacteria is expected to reveal key bacterial virulence mechanisms and provide opportunities to understand host resistance to mycobacterial infection. Understanding differences within the M. tuberculosis complex and the evolutionary forces shaping these differences is important for investigating the basis of its success as both a symbiont and a pathogen.

Host gene expression for Mycobacterium avium subsp. paratuberculosis infection in human THP-1 macrophages.

PubMed

Shin, Min-Kyoung; Shin, Seung Won; Jung, Myunghwan; Park, Hongtae; Park, Hyun-Eui; Yoo, Han Sang

2015-07-01

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, which causes considerable economic loss in the dairy industry and has a possible relationship to Crohn's disease (CD) in humans. As MAP has been detected in retail pasteurized milk samples, its transmission via milk is of concern. Despite its possible role in the etiology of CD, there have been few studies examining the interactions between MAP and human cells. In the current study, we applied Ingenuity Pathway Analysis to the transcription profiles generated from a murine model with MAP infection as part of a previously conducted study. Twenty-one genes were selected as potential host immune responses, compared with the transcriptional profiles in naturally MAP-infected cattle, and validated in MAP-infected human monocyte-derived macrophage THP-1 cells. Of these, the potential host responses included up-regulation of genes related to immune response (CD14, S100A8, S100A9, LTF, HP and CHCIL3), up-regulation of Th1-polarizing factor (CCL4, CCL5, CXCL9 and CXCL10), down-regulation of genes related to metabolism (ELANE, IGF1, TCF7L2 and MPO) and no significant response of other genes (GADD45a, GPNMB, HMOX1, IFNG and NQO1) in THP-1 cells infected with MAP. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of host-pathogen modulators of autophagy during Mycobacterium Tuberculosis infection and therapeutic repercussions.

PubMed

Khan, Arshad; Jagannath, Chinnaswamy

2017-09-03

Mycobacterium tuberculosis is one of the most deadly human pathogens known today in modern world, responsible for about 1.5 million deaths annually. Development of TB disease occurs only in 1 out of 10 individuals exposed to the pathogen which indicates that the competent host defense mechanisms exist in majority of the hosts to control the infection. In the last decade, autophagy has emerged as a key host immune defense mechanism against intracellular M. tuberculosis infection. Autophagy has been demonstrated not only as an effective antimicrobial mechanism for the clearance of M. tuberculosis, but the process has also been suggested to prevent excessive inflammation to avoid the adverse effects of infection on host. Nevertheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to compromise the optimal functioning of host autophagic machinery. This review describes an overview of the various host signaling pathways such as pattern recognition receptors, cytokines, nutrient starvation and other cellular stress that have been implicated in induction of autophagy during M. tuberculosis infection. The review also chalk out the complex interplay of several bacterial factors of M. tuberculosis that are known to be involved in compromising autophagy mediated defense of the host. A comprehensive understanding of the interaction of bacterial and host factors at the intersections of autophagic pathways could provide integrative insights for the development of autophagy-based prophylactics and novel therapeutic interventions for TB.

Analysis of the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis in four countries.

PubMed

Han, Xiang Y; Aung, Fleur M; Choon, Siew Eng; Werner, Betina

2014-10-01

To differentiate the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis and correlate them with geographic distribution and clinicopathologic features. Species-specific polymerase chain reactions were used to detect each bacillus in archived skin biopsy specimens from patients with leprosy from Brazil (n = 52), Malaysia (n = 31), Myanmar (n = 9), and Uganda (n = 4). Findings were correlated with clinical and pathologic data. Etiologic species was detected in 46 of the 52 Brazilian patients, including 36 patients with M leprae, seven with M lepromatosis, and three with both bacilli. The seven patients with sole M lepromatosis all had tuberculoid leprosy, whereas only nine of the 36 patients infected with M leprae exhibited this type, and the rest were lepromatous (P < .001). All patients with dual infections had lepromatous leprosy. Of the nine patients from Myanmar, six were test positive: four with M leprae and two with M lepromatosis. Of the Malaysian and Ugandan patients, only M leprae was detected in 27 of the 31 Malaysians and two of the four Ugandans. The leprosy agents vary in geographic distribution. Finding M lepromatosis in Brazil and Myanmar suggests wide existence of this newly discovered species. The leprosy manifestations likely vary with the etiologic agents. Copyright© by the American Society for Clinical Pathology.

Frequency of Mycobacterium chimaera among Belgian patients, 2015.

PubMed

Soetaert, Karine; Vluggen, Christelle; André, Emmanuel; Vanhoof, Raymond; Vanfleteren, Brigitte; Mathys, Vanessa

2016-11-01

Mycobacterium chimaera arouses an increasing public health concern, as this non-tuberculous mycobacterium (NTM) has recently been associated with life-threatening cardiac infections. M. chimaera and Mycobacteriumintracellulare are genetically very close but recently appeared to present different epidemiological and clinical significance. Therefore, it has become important for laboratories to use adequate techniques allowing precise species identification. To date, most commercially available laboratory assays cannot distinguish them and erroneously identify M. chimaera as M. intracellulare. We performed a re-analysis of the 149 M. intracellulare strains received by the Belgian National Reference Laboratory using 16S rRNA gene sequencing, representing 25 % of all NTM collected in 2015. We found that M. chimaera represents the majority (n=94, 63 %) of the previous M. intracellulare. This study reports the large presence of M. intracellulare/chimaera among Belgian patients infected by an NTM and the predominance of the species M. chimaera among this group. This study also stresses the public health importance of M. chimaera and demonstrates the inability of commonly used laboratory techniques to correctly diagnose these infections.

Expression of Cathelicidin LL-37 during Mycobacterium tuberculosis Infection in Human Alveolar Macrophages, Monocytes, Neutrophils, and Epithelial Cells▿

PubMed Central

Rivas-Santiago, Bruno; Hernandez-Pando, Rogelio; Carranza, Claudia; Juarez, Esmeralda; Contreras, Juan Leon; Aguilar-Leon, Diana; Torres, Martha; Sada, Eduardo

2008-01-01

The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis. PMID:18160480

Mycobacterium tuberculosis Metabolism

PubMed Central

Warner, Digby F.

2015-01-01

Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

Low Dose Aerosol Fitness at the Innate Phase of Murine Infection Better Predicts Virulence amongst Clinical Strains of Mycobacterium tuberculosis

PubMed Central

Caceres, Neus; Llopis, Isaac; Marzo, Elena; Prats, Clara; Vilaplana, Cristina; de Viedma, Dario Garcia; Samper, Sofía; Lopez, Daniel; Cardona, Pere-Joan

2012-01-01

Background Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 104 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 102 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. Conclusions/Significance The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism of the induction of active TB derived from the dynamic hypothesis of latent tuberculosis infection. PMID:22235258

Regulatory T cells: Friends or foe in human Mycobacterium leprae infection?

PubMed

Chaves, Ana T; Ribeiro-Junior, Atvaldo F; Lyon, Sandra; Medeiros, Nayara I; Cassirer-Costa, Fábio; Paula, Karina S; Alecrim, Edilamar S; Menezes, Cristiane A S; Correa-Oliveira, Rodrigo; Rocha, Manoel O C; Gomes, Juliana A S

Regulatory T cells (Tregs) are known to control immune responses by suppressing the antigen-presenting and effector T cells. Some mechanisms adopted by Tregs in combating Mycobacterium infections have been proposed. Nevertheless, in M. leprae infection, also known as leprosy or Hansen's disease, the role of Tregs has not been completely elucidated. Using multicolor flow cytometry, we evaluated the expression of different cell surface and intracellular molecules present in Tregs from peripheral blood samples of leprosy patients. Before initiating treatment, thirteen new cases of leprosy were grouped according to the Ridley-Jopling classification in to the paucibacilary (PB) or multibacilary (MB) group. Fifteen non-infected individuals (NI) were included as control subjects. Tregs were higher in the MB group than in the NI group. Tregs also co-expressed high amounts of PD1 and PDL-1, indicating that these cells could induce apoptosis of effector cells and simultaneously prevent their own apoptosis. Our data showed that compared to the NI group, Tregs from the PB group expressed higher levels of CD95L, which may be associated with other apoptotic pathways that may decrease Tregs in these patients. Correlation analysis reinforced that PD1 and CD95L are efficient apoptosis' pathway that decreased levels of Tregs in the NI and PB groups. We also observed significant differences in cytokine expression of Tregs from the PB and MB groups. Compared to the NI group, Tregs from the MB group showed higher IL-17 expression; however, compared to the PB group, the expression of IL-10 in Tregs from the MB group was lower, suggesting inefficient control of inflammation. Therefore, we concluded that different pathways were involved in Treg-induced suppression of leprosy. Moreover, Treg-mediated regulation of inflammation via IL-10 and IL-17 expression in leprosy patients was inefficient. Thus, we propose that during M. leprae infection, Tregs may impair the immune responses elicited

Molecular Characteristics and Drug Susceptibility of Mycobacterium tuberculosis Isolates from Patients Co-infected with Human Immunodeficiency Virus in Beijing, China.

PubMed

Liu, Jie; Wang, Hui Zhu; Lian, Lu Lu; Yu, Yan Hua; Zhao, Xiu Qin; Guo, Cai Ping; Liu, Hai Can; Liu, Shu Mei; Zhao, Hui; Zeng, Zhao Ying; Zhao, Xiu Ying; Wan, Kang Lin

2015-03-01

70 clinical Mycobacterium tuberculosis strains isolated from AIDS patients in two HIV/AIDS referral hospitals in Beijing were used in this study. M. tuberculosis and non-tuberculosis mycobacterium (NTM) were identified by using multi-locus PCR. M. tuberculosis was genotyped by using 15-locus MIRU-VNTR technique and spoligotyping afterwards. Meanwhile, the drug susceptibilities of the strains to the four first-line anti TB drugs (rifampin, isoniazid, streptomycin, and ethambutol) and the four second-line anti-TB drugs (capreomycin, kanamycin, ofloxacin, and ethionanide) were tested with proportional method. In this study, M. tuberculosis and NTM strains isolated from AIDS patients with TB-like symptoms were identified and genotyping analysis indicated that Beijing genotype was the predominant genotype. In addition, the prevalence of drug-resistant TB, especially the prevalence of XDR-TB, was higher than that in TB patients without HIV infection. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Thrombomodulin Mutations in Atypical Hemolytic–Uremic Syndrome

PubMed Central

Delvaeye, Mieke; Noris, Marina; De Vriese, Astrid; Esmon, Charles T.; Esmon, Naomi L.; Ferrell, Gary; Del-Favero, Jurgen; Plaisance, Stephane; Claes, Bart; Lambrechts, Diether; Zoja, Carla; Remuzzi, Giuseppe; Conway, Edward M.

2012-01-01

BACKGROUND The hemolytic–uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. The common form of the syndrome is triggered by infection with Shiga toxin–producing bacteria and has a favorable outcome. The less common form of the syndrome, called atypical hemolytic–uremic syndrome, accounts for about 10% of cases, and patients with this form of the syndrome have a poor prognosis. Approximately half of the patients with atypical hemolytic–uremic syndrome have mutations in genes that regulate the complement system. Genetic factors in the remaining cases are unknown. We studied the role of thrombomodulin, an endothelial glycoprotein with anticoagulant, antiinflammatory, and cytoprotective properties, in atypical hemolytic–uremic syndrome. METHODS We sequenced the entire thrombomodulin gene (THBD) in 152 patients with atypical hemolytic–uremic syndrome and in 380 controls. Using purified proteins and cell-expression systems, we investigated whether thrombomodulin regulates the complement system, and we characterized the mechanisms. We evaluated the effects of thrombomodulin missense mutations associated with atypical hemolytic–uremic syndrome on complement activation by expressing thrombomodulin variants in cultured cells. RESULTS Of 152 patients with atypical hemolytic–uremic syndrome, 7 unrelated patients had six different heterozygous missense THBD mutations. In vitro, thrombomodulin binds to C3b and factor H (CFH) and negatively regulates complement by accelerating factor I–mediated inactivation of C3b in the presence of cofactors, CFH or C4b binding protein. By promoting activation of the plasma procarboxypeptidase B, thrombomodulin also accelerates the inactivation of anaphylatoxins C3a and C5a. Cultured cells expressing thrombomodulin variants associated with atypical hemolytic–uremic syndrome had diminished capacity to inactivate C3b and to activate procarboxypeptidase B and were

Clinical Profile of Atypical Manifestations of Dengue Fever.

PubMed

Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

2016-06-01

To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. All children (0-12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of

Mycobacterium kansasii Isolated from Tuberculinpositive Rhesus Macaques (Macaca mulatta) in the Absence of Disease.

PubMed

Shipley, Steven T; Johnson, David K; Roodgar, Morteza; Smith, David Glenn; Montgomery, Charles A; Lloyd, Steven M; Higgins, James A; Kriel, Edwin H; Klein, Hilton J; Porter, William P; Nazareno, Jerome B; Houghton, Paul W; Panda, Aruna; DeTolla, Louis J

2017-08-01

Mycobacterial infections are of primary health concern in NHP colonies in biomedical research. NHP are constantly monitored and screened for Mycobacterium spp. We report 6 Chinese-origin rhesus macaques infected with Mycobacterium kansasii that exhibited positive tuberculin skin tests in the absence of disease. Two of these macaques were being used for research purposes; the remaining 4 macaques were residing at the contract quarantine company. Histopathology and acid-fast staining of fixed tissues from all macaques showed that all were free of disease. Thoracic radiographs were negative for any signs of disease or infection. Samples from bronchial lavage and tissues including lung, spleen, hilar and mesenteric lymph nodes tested negative by PCR assay for Mycobacterium spp. One of the research macaques tested culture-positive for M. kansasii and a poorly characterized M. avium complex organism. One macaque from the contract quarantine facility tested culture positive for M. kansasii. Genomic testing and target gene RNA expression analysis of the 2 M. kansasii isolates were performed to evaluate possible kinship and affected genes that might contribute to susceptibility to mycobacterial infection. Genotyping of the 2 isolates revealed 2 genetically distinct strains (strains 1 and 4). The presence of positive tuberculin skin tests in the absence of disease raises serious concerns regarding diagnostic methods used for infected NHP.

Rapid-Growing Mycobacteria Infections in Medical Tourists: Our Experience and Literature Review.

PubMed

Singh, Mansher; Dugdale, Caitlin M; Solomon, Isaac H; Huang, Anne; Montgomery, Mary W; Pomahac, Bohdan; Yawetz, Sigal; Maguire, James H; Talbot, Simon G

2016-09-01

"Medical tourism" has gained popularity over the past few decades. This is particularly common with patients seeking elective cosmetic surgery in the developing world. However, the risk of severe and unusual infectious complications appears to be higher than for patients undergoing similar procedures in the United States. The authors describe their experience with atypical mycobacterial infections in cosmetic surgical patients returning to the United States postoperatively. A review of patient medical records presenting with infectious complications after cosmetic surgery between January 2010 and July 2015 was performed. Patients presenting with mycobacterial infections following cosmetic surgery were reviewed in detail. An extensive literature review was performed for rapid-growing mycobacteria (RGM) related to cosmetic procedures. Between January 2010 and July 2015, three patients presented to our institution with culture-proven Mycobacterium abscessus at the sites of recent cosmetic surgery. All had surgery performed in the developing world. The mean age of these patients was 36 years (range, 29-44 years). There was a delay of up to 16 weeks between the initial presentation and correct diagnosis. All patients were treated with surgical drainage and combination antibiotics with complete resolution. We present series of patients with mycobacterial infections after cosmetic surgery in the developing world. This may be related to the endemic nature of these bacteria and/or inadequate sterilization or sterile technique. Due to low domestic incidence of these infections, diagnosis may be difficult and/or delayed. Consulting physicians should have a low threshold to consider atypical etiologies in such scenarios. 5 Therapeutic. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Characterizing the risk of infection from Mycobacterium tuberculosis in commercial passenger aircraft using quantitative microbial risk assessment.

PubMed

Jones, Rachael M; Masago, Yoshifumi; Bartrand, Timothy; Haas, Charles N; Nicas, Mark; Rose, Joan B

2009-03-01

Quantitative microbial risk assessment was used to predict the likelihood and spatial organization of Mycobacterium tuberculosis (Mtb) transmission in a commercial aircraft. Passenger exposure was predicted via a multizone Markov model in four scenarios: seated or moving infectious passengers and with or without filtration of recirculated cabin air. The traditional exponential (k = 1) and a new exponential (k = 0.0218) dose-response function were used to compute infection risk. Emission variability was included by Monte Carlo simulation. Infection risks were higher nearer and aft of the source; steady state airborne concentration levels were not attained. Expected incidence was low to moderate, with the central 95% ranging from 10(-6) to 10(-1) per 169 passengers in the four scenarios. Emission rates used were low compared to measurements from active TB patients in wards, thus a "superspreader" emitting 44 quanta/h could produce 6.2 cases or more under these scenarios. Use of respiratory protection by the infectious source and/or susceptible passengers reduced infection incidence up to one order of magnitude.

Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular infection offers insight into coordinated virulence.

PubMed

Barczak, Amy K; Avraham, Roi; Singh, Shantanu; Luo, Samantha S; Zhang, Wei Ran; Bray, Mark-Anthony; Hinman, Amelia E; Thompson, Matthew; Nietupski, Raymond M; Golas, Aaron; Montgomery, Paul; Fitzgerald, Michael; Smith, Roger S; White, Dylan W; Tischler, Anna D; Carpenter, Anne E; Hung, Deborah T

2017-05-01

A key to the pathogenic success of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is the capacity to survive within host macrophages. Although several factors required for this survival have been identified, a comprehensive knowledge of such factors and how they work together to manipulate the host environment to benefit bacterial survival are not well understood. To systematically identify Mtb factors required for intracellular growth, we screened an arrayed, non-redundant Mtb transposon mutant library by high-content imaging to characterize the mutant-macrophage interaction. Based on a combination of imaging features, we identified mutants impaired for intracellular survival. We then characterized the phenotype of infection with each mutant by profiling the induced macrophage cytokine response. Taking a systems-level approach to understanding the biology of identified mutants, we performed a multiparametric analysis combining pathogen and host phenotypes to predict functional relationships between mutants based on clustering. Strikingly, mutants defective in two well-known virulence factors, the ESX-1 protein secretion system and the virulence lipid phthiocerol dimycocerosate (PDIM), clustered together. Building upon the shared phenotype of loss of the macrophage type I interferon (IFN) response to infection, we found that PDIM production and export are required for coordinated secretion of ESX-1-substrates, for phagosomal permeabilization, and for downstream induction of the type I IFN response. Multiparametric clustering also identified two novel genes that are required for PDIM production and induction of the type I IFN response. Thus, multiparametric analysis combining host and pathogen infection phenotypes can be used to identify novel functional relationships between genes that play a role in infection.

A Novel Enzyme-Linked Immunosorbent Assay for Diagnosis of Mycobacterium avium subsp. paratuberculosis Infections (Johne's Disease) in Cattle

PubMed Central

Speer, C. A.; Scott, M. Cathy; Bannantine, John P.; Waters, W. Ray; Mori, Yasuyuki; Whitlock, Robert H.; Eda, Shigetoshi

2006-01-01

Enzyme-linked immunosorbent assays (ELISAs) for the diagnosis of Johne's disease (JD), caused by Mycobacterium avium subsp. paratuberculosis, were developed using whole bacilli treated with formaldehyde (called WELISA) or surface antigens obtained by treatment of M. avium subsp. paratuberculosis bacilli with formaldehyde and then brief sonication (called SELISA). ELISA plates were coated with either whole bacilli or sonicated antigens and tested for reactivity against serum obtained from JD-positive and JD-negative cattle or from calves experimentally inoculated with M. avium subsp. paratuberculosis, Mycobacterium avium subsp. avium, or Mycobacterium bovis. Because the initial results obtained from the WELISA and SELISA were similar, most of the subsequent experiments reported herein were performed using the SELISA method. To optimize the SELISA test, various concentrations (3.7 to 37%) of formaldehyde and intervals of sonication (2 to 300 s) were tested. With an increase in formaldehyde concentration and a decreased interval of sonication, there was a concomitant decrease in nonspecific binding by the SELISA. SELISAs prepared by treating M. avium subsp. paratuberculosis with 37% formaldehyde and then a 2-s burst of sonication produced the greatest difference (7×) between M. avium subsp. paratuberculosis-negative and M. avium subsp. paratuberculosis-positive serum samples. The diagnostic sensitivity and specificity for JD by the SELISA were greater than 95%. The SELISA showed subspecies-specific detection of M. avium subsp. paratuberculosis infections in calves experimentally inoculated with M. avium subsp. paratuberculosis or other mycobacteria. Based on diagnostic sensitivity and specificity, the SELISA appears superior to the commercial ELISAs routinely used for the diagnosis of JD. PMID:16682472

Multinucleated giant cell cytokine expression in pulmonary granulomas of cattle experimentally infected with Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Pathogenic mycobacteria of the Mycobacterium tuberculosis complex such as Mycobacterium bovis, induce a characteristic lesion known as a granulomas. Granulomas represent a specific host response to chronic antigenic stimuli, such as foreign bodies, certain bacterial components, or persistent pathoge...

Comparison of prevalence estimation of Mycobacterium avium subsp. paratuberculosis infection by sampling slaughtered cattle with macroscopic lesions vs. systematic sampling.

PubMed

Elze, J; Liebler-Tenorio, E; Ziller, M; Köhler, H

2013-07-01

The objective of this study was to identify the most reliable approach for prevalence estimation of Mycobacterium avium ssp. paratuberculosis (MAP) infection in clinically healthy slaughtered cattle. Sampling of macroscopically suspect tissue was compared to systematic sampling. Specimens of ileum, jejunum, mesenteric and caecal lymph nodes were examined for MAP infection using bacterial microscopy, culture, histopathology and immunohistochemistry. MAP was found most frequently in caecal lymph nodes, but sampling more tissues optimized the detection rate. Examination by culture was most efficient while combination with histopathology increased the detection rate slightly. MAP was detected in 49/50 animals with macroscopic lesions representing 1.35% of the slaughtered cattle examined. Of 150 systematically sampled macroscopically non-suspect cows, 28.7% were infected with MAP. This indicates that the majority of MAP-positive cattle are slaughtered without evidence of macroscopic lesions and before clinical signs occur. For reliable prevalence estimation of MAP infection in slaughtered cattle, systematic random sampling is essential.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

PubMed

Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R; Sterling, Timothy R; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-12-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone. Copyright ©ERS 2015.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

PubMed Central

Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D. Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh Jr, C. Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J.; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R.; Sterling, Timothy R.; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J.; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K.; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-01-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. PMID:26405286

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection.

PubMed

Booty, Matthew G; Barreira-Silva, Palmira; Carpenter, Stephen M; Nunes-Alves, Cláudio; Jacques, Miye K; Stowell, Britni L; Jayaraman, Pushpa; Beamer, Gillian; Behar, Samuel M

2016-11-07

IL-21 is produced predominantly by activated CD4 + T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (γ c ) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8 + T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4 + and CD8 + T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R -/- mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R -/- T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

PubMed Central

Booty, Matthew G.; Barreira-Silva, Palmira; Carpenter, Stephen M.; Nunes-Alves, Cláudio; Jacques, Miye K.; Stowell, Britni L.; Jayaraman, Pushpa; Beamer, Gillian; Behar, Samuel M.

2016-01-01

IL-21 is produced predominantly by activated CD4+ T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (γc) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8+ T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4+ and CD8+ T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R−/− mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R−/− T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis. PMID:27819295

Isolation and characterization of atypical Listeria monocytogenes associated with a canine urinary tract infection.

PubMed

Palerme, Jean-Sébastien; Pan, Po Ching; Parsons, Cameron T; Kathariou, Sophia; Ward, Todd J; Jacob, Megan E

2016-09-01

Listeria monocytogenes, a well-described cause of encephalitis and abortion in ruminants and of food-borne illness in humans, is rarely associated with disease in companion animals. A case of urinary tract infection associated with an atypical, weakly hemolytic L. monocytogenes strain is described in a diabetic dog. The serotype of the L. monocytogenes isolate was determined to be 1/2a (3a), with the multilocus genotyping pattern 2.72_1/2a. A nucleotide substitution (Gly145Asp) was detected at residue 145 in the promoter prfA region. This residue is within the critical helix-turn-helix motif of PrfA. The source of the L. monocytogenes strain remains unknown, and the dog recovered after a 4-week course of cephalexin (30 mg/kg orally twice daily). © 2016 The Author(s).

Analysis of the Bovine Monocyte-Derived Macrophage Response to Mycobacterium avium Subspecies Paratuberculosis Infection Using RNA-seq.

PubMed

Casey, Maura E; Meade, Kieran G; Nalpas, Nicolas C; Taraktsoglou, Maria; Browne, John A; Killick, Kate E; Park, Stephen D E; Gormley, Eamonn; Hokamp, Karsten; Magee, David A; MacHugh, David E

2015-01-01

Johne's disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP), is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne's disease. Here, we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM) transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a 6-h infection time course with non-infected controls. We observed 245 and 574 differentially expressed (DE) genes in MAP-infected versus non-infected control samples (adjusted P value ≤0.05) at 2 and 6 h post-infection, respectively. Functional analyses of these DE genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the IL-10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix(®) microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection.

Analysis of the Bovine Monocyte-Derived Macrophage Response to Mycobacterium avium Subspecies Paratuberculosis Infection Using RNA-seq

PubMed Central

Casey, Maura E.; Meade, Kieran G.; Nalpas, Nicolas C.; Taraktsoglou, Maria; Browne, John A.; Killick, Kate E.; Park, Stephen D. E.; Gormley, Eamonn; Hokamp, Karsten; Magee, David A.; MacHugh, David E.

2015-01-01

Johne’s disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP), is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne’s disease. Here, we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM) transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a 6-h infection time course with non-infected controls. We observed 245 and 574 differentially expressed (DE) genes in MAP-infected versus non-infected control samples (adjusted P value ≤0.05) at 2 and 6 h post-infection, respectively. Functional analyses of these DE genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the IL-10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix® microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection. PMID:25699042

The Leprosy Agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico

PubMed Central

Han, Xiang Y.; Sizer, Kurt Clement; Velarde-Félix, Jesús S.; Frias-Castro, Luis O.; Vargas-Ocampo, Francisco

2011-01-01

Summary Background Mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named Mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in Mexico. Methods We sought to differentiate the leprosy agents among 120 Mexican patients with various clinical forms of leprosy and to compare their relative prevalence and disease features. Archived skin biopsy specimens from these patients were tested for both M. leprae and M. lepromatosis using polymerase chain reaction-based species-specific assays. Results Eighty-seven (72.5%) patients were confirmed for etiologic species, including 55 with M. lepromatosis, 18 with M. leprae, and 14 with both organisms. The endemic regions of each agent differed but overlapped. Patients with M. lepromatosis were younger and from more states, and their clinical diagnoses included 13 DLL, 34 lepromatous leprosy (LL), and eight other forms of leprosy. By contrast, the diagnoses of patients with M. leprae included none DLL, 15 LL and three other forms. Thus, M. lepromatosis caused DLL specifically (p=0.023). Patients with M. lepromatosis also showed more variable skin lesions and the extremities were the commonest biopsy sites. Finally, patients with dual infections manifested all clinical forms and accounted for 16.1% of all species-confirmed cases. Conclusions M. lepromatosis is another cause of leprosy and is probably more prevalent than M. leprae in Mexico. It mainly causes LL and also specifically DLL. Dual infections caused by both species may occur in endemic area. PMID:22788812

Experimental Infection of Rhodnius prolixus (Hemiptera, Triatominae) with Mycobacterium leprae Indicates Potential for Leprosy Transmission

PubMed Central

Neumann, Arthur da Silva; Dias, Felipe de Almeida; Ferreira, Jéssica da Silva; Fontes, Amanda Nogueira Brum; Rosa, Patricia Sammarco; Macedo, Rafael Enrique; Oliveira, José Henrique; Teixeira, Raquel Lima de Figueiredo; Pessolani, Maria Cristina Vidal; Moraes, Milton Ozório; Suffys, Philip Noel; Oliveira, Pedro L.; Sorgine, Marcos Henrique Ferreira; Lara, Flavio Alves

2016-01-01

Leprosy is a chronic dermato-neurological disease caused by infection with Mycobacterium leprae. In 2013 almost 200,000 new cases of leprosy were detected around the world. Since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. Although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. In the present work, we experimentally investigated the hypothesis that the mosquitoes Aedes aegypti and Culex quinquefasciatus and the hemiptera Rhodnius prolixus act as leprosy vectors. By means of real-time PCR quantification of M. leprae 16SrRNA, we found that M. leprae remained viable inside the digestive tract of Rhodnius prolixus for 20 days after oral infection. In contrast, in the gut of both mosquito species tested, we were not able to detect M. leprae RNA after a similar period of time. Inside the kissing bug Rhodnius prolixus digestive tract, M. leprae was initially restricted to the anterior midgut, but gradually moved towards the hindgut, in a time course reminiscent of the life cycle of Trypanosoma cruzi, a well-known pathogen transmitted by this insect. The maintenance of M. leprae infectivity inside the digestive tract of this kissing bug is further supported by successful mice footpad inoculation with feces collected 20 days after infection. We conclude that Rhodnius prolixus defecate infective M. leprae, justifying the evaluation of the presence of M. leprae among sylvatic and domestic kissing bugs in countries endemic for leprosy. PMID:27203082

Experimental Infection of Rhodnius prolixus (Hemiptera, Triatominae) with Mycobacterium leprae Indicates Potential for Leprosy Transmission.

PubMed

Neumann, Arthur da Silva; Dias, Felipe de Almeida; Ferreira, Jéssica da Silva; Fontes, Amanda Nogueira Brum; Rosa, Patricia Sammarco; Macedo, Rafael Enrique; Oliveira, José Henrique; Teixeira, Raquel Lima de Figueiredo; Pessolani, Maria Cristina Vidal; Moraes, Milton Ozório; Suffys, Philip Noel; Oliveira, Pedro L; Sorgine, Marcos Henrique Ferreira; Lara, Flavio Alves

2016-01-01

Leprosy is a chronic dermato-neurological disease caused by infection with Mycobacterium leprae. In 2013 almost 200,000 new cases of leprosy were detected around the world. Since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. Although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. In the present work, we experimentally investigated the hypothesis that the mosquitoes Aedes aegypti and Culex quinquefasciatus and the hemiptera Rhodnius prolixus act as leprosy vectors. By means of real-time PCR quantification of M. leprae 16SrRNA, we found that M. leprae remained viable inside the digestive tract of Rhodnius prolixus for 20 days after oral infection. In contrast, in the gut of both mosquito species tested, we were not able to detect M. leprae RNA after a similar period of time. Inside the kissing bug Rhodnius prolixus digestive tract, M. leprae was initially restricted to the anterior midgut, but gradually moved towards the hindgut, in a time course reminiscent of the life cycle of Trypanosoma cruzi, a well-known pathogen transmitted by this insect. The maintenance of M. leprae infectivity inside the digestive tract of this kissing bug is further supported by successful mice footpad inoculation with feces collected 20 days after infection. We conclude that Rhodnius prolixus defecate infective M. leprae, justifying the evaluation of the presence of M. leprae among sylvatic and domestic kissing bugs in countries endemic for leprosy.

Why you should ask your patients about their fishing hobbies.

PubMed

Bakker, C V; Kardaun, S H; Wilting, K R; Diercks, G F H; Horváth, B

2013-09-01

Patients who use immunosuppressive agents, in particular medication that blocks tumour necrosis factor-a, are at risk for mycobacterial infections. Besides the typical Mycobacterium tuberculosis infection, a lso a typical mycobacterial disease may occur. Here we demonstrate two patients with such atypical mycobacterial infection due to swimming and fishing water contact. We propose that patients, before starting with immunosuppressive therapy, are counselled about risk factors for mycobacterial disease.

Molecular and epidemiological population-based integrative analysis of human and animal Mycobacterium bovis infections in a low-prevalence setting.

PubMed

Palacios, Juan José; Navarro, Yurena; Romero, Beatriz; Penedo, Ana; Menéndez González, Ángela; Pérez Hernández, M Dolores; Fernández-Verdugo, Ana; Copano, Francisca; Torreblanca, Aurora; Bouza, Emilio; Domínguez, Lucas; de Juan, Lucía; García-de-Viedma, Darío

2016-11-15

Human Mycobacterium bovis infections are considered to be due to reactivations, when involve elderly people, or to recent transmissions, when exposure is occupational. We determined the cause of M. bovis infections by genotyping M. bovis isolates in a population-based study integrating human and animal databases. Among the 1,586 tuberculosis (TB) cases in Asturias, Northern Spain (1,080,000 inhabitants), 1,567 corresponded to M. tuberculosis and 19 to M. bovis. The number of human isolates sharing genotype with cattle isolates was higher than expected (47%) for a setting with low prevalence of bovine TB and efficient control programs in cattle. The risk of exposure to infected animals was probable/possible in most of these matched cases (77.7%). Recent transmission was the likely explanation of most M. bovis infections in elderly people. A potential human-to-human transmission was found. Our study illustrates a model of collaboration between human and animal health professionals to provide a precise snapshot of the transmission of M. bovis in the human-animal interface. Copyright © 2016 Elsevier B.V. All rights reserved.

Filarial infection modulates the immune response to Mycobacterium tuberculosis through expansion of CD4+ IL-4 memory T cells

PubMed Central

Chatterjee, Soumya; Clark, Carolyn E.; Lugli, Enrico; Roederer, Mario; Nutman, Thomas B.

2015-01-01

Exaggerated CD4+T helper 2-specific cytokine producing memory T cell responses developing concomitantly with a T helper1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis (Mtb). To assess the dynamics of antigen (Ag)-specific memory T cell compartments in the context of filarial infection we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial -infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial (BmA) or with the Mycobacterium tuberculosis (Mtb)-specific Ag CFP10. Our data demonstrated that the Inf group not only had a marked increase in BmA-specific CD4+IL-4+ cells (Median net frequency compared to baseline (Fo)=0.09% vs. 0.01%, p=0.038) but also to CFP10 (Fo =0.16% vs. 0.007%, p=0.04) and Staphylococcal Enterotoxin B (SEB) (Fo =0.49% vs. 0.26%, p=0.04). The Inf subjects showed a BmA-specific expansion of CD4+CD45RO+IL-4+ producing central memory (TCM, CD45RO+CCR7+CD27+) (Fo =1.1% vs. 0.5%, p=0.04) as well as effector memory (TEM CD45RO+CCR7-CD27-) (Fo =1.5% vs. 0.2%, p=0.03) with a similar but non-significant response to CFP10. In addition, there was expansion of CD4+ IL-4+ CD45RA+ CCR7+CD27+ (naïve-like) in Inf individuals compared to Uninf subjects. Among Inf subjects with definitive latent tuberculosis , there were no differences in frequencies of IL-4 producing cells within any of the memory compartments compared to the Uninf group. Our data suggest that filarial infection induces antigen-specific, exaggerated IL-4 responses in distinct T cell memory compartments to Mtb-specific antigens, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to Mtb. PMID:25667413

Mycobacterium tuberculosis in Wild Asian Elephants, Southern India.

PubMed

Zachariah, Arun; Pandiyan, Jeganathan; Madhavilatha, G K; Mundayoor, Sathish; Chandramohan, Bathrachalam; Sajesh, P K; Santhosh, Sam; Mikota, Susan K

2017-03-01

We tested 3 ild Asian elephants (Elephas maximus) in southern India and confirmed infection in 3 animals with Mycobacterium tuberculosis, an obligate human pathogen, by PCR and genetic sequencing. Our results indicate that tuberculosis may be spilling over from humans (reverse zoonosis) and emerging in wild elephants.

Accurate differentiation of Mycobacterium chimaera from Mycobacterium intracellulare by MALDI-TOF MS analysis.

PubMed

Pranada, Arthur B; Witt, Ellen; Bienia, Michael; Kostrzewa, Markus; Timke, Markus

2017-05-01

The increasing number of infections caused by nontuberculous mycobacteria (NTM) has prompted the need for rapid and precise identification methods of these pathogens. Several studies report the applicability of MALDI-TOF mass spectrometry (MS) for identification of NTM. However, some closely related species have very similar spectral mass fingerprints, and until recently, Mycobacterium chimaera and M. intracellulare could not be separated from each other by MALDI-TOF MS. The conventional identification methods used in routine diagnostics have similar limitations. Recently, the differentiation of these two species within the Mycobacterium avium complex has become increasingly important due to reports of M. chimaera infections related to open heart surgery in Europe and in the USA. In this report, a method for the distinct differentiation of M. chimaera and M. intracellulare using a more detailed analysis of MALDI-TOF mass spectra is presented. Species-specific peaks could be identified and it was possible to assign all isolates (100 %) from reference strain collections as well as clinical isolates to the correct species. We have developed a model for the accurate identification of M. chimaera and M. intracellulare by MALDI-TOF MS. This approach has the potential for routine use in microbiology laboratories, as the model itself can be easily implemented into the software of the currently available systems by MALDI-TOF MS manufacturers.

Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands.

PubMed

Nebenzahl-Guimaraes, Hanna; Verhagen, Lilly M; Borgdorff, Martien W; van Soolingen, Dick

2015-10-01

The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Mycobacterium paratuberculosis, Mycobacterium smegmatis, and lipopolysaccharide induce different transcriptional and post-transcriptional regulation of the IRG1 gene in murine macrophages.

PubMed

Basler, Tina; Jeckstadt, Sabine; Valentin-Weigand, Peter; Goethe, Ralph

2006-03-01

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic enteritis in ruminants. In addition, MAP is presently the most favored pathogen linked to Crohn's disease. In this study, we were interested in dissecting the molecular mechanisms of macrophage activation or deactivation after infection with MAP. By subtractive hybridization of cDNAs, we identified the immune-responsive gene 1 (IRG1), which was expressed substantially higher in lipopolysaccharide (LPS)-stimulated than in MAP-infected murine macrophage cell lines. A nuclear run-on transcription assay revealed that the IRG1 gene was activated transcriptionally in LPS-stimulated and MAP-infected macrophages with higher expression in LPS-stimulated cells. Analysis of post-transcriptional regulation demonstrated that IRG1 mRNA stability was increased in LPS-stimulated but not in MAP-infected macrophages. Furthermore, IRG1 gene expression of macrophages infected with the nonpathogenic Mycobacterium smegmatis differed from those of LPS-stimulated and MAP-infected macrophages. At 2 h postinfection, M. smegmatis-induced IRG1 gene expression was as low as in MAP-infected, and 8 h postinfection, it increased nearly to the level in LPS-stimulated macrophages. Transient transfection experiments revealed similar IRG1 promoter activities in MAP- and M. smegmatis-infected cells. Northern analysis demonstrated increased IRG1 mRNA stability in M. smegmatis-infected macrophages. IRG1 mRNA stabilization was p38 mitogen-activated protein kinase-independent. Inhibition of protein synthesis revealed that constitutively expressed factors seemed to be responsible for IRG1 mRNA destabilization. Thus, our data demonstrate that transcriptional and post-transcriptional mechanisms are responsible for a differential IRG1 gene expression in murine macrophages treated with LPS, MAP, and M. smegmatis.

Spontaneous Regression of Pulmonary Nodules Presenting as Epstein-Barr Virus-related Atypical Infectious Mononucleosis.

PubMed

Shinozuka, Jun; Awaguni, Hitoshi; Tanaka, Shin-Ichiro; Makino, Shigeru; Maruyama, Rikken; Inaba, Tohru; Imashuku, Shinsaku

2016-07-01

Pulmonary nodules associated with Epstein-Barr virus (EBV)-related atypical infectious mononucleosis have rarely been described. A 12-year-old Japanese boy, upon admission, revealed multiple small round nodules (a total of 7 nodules in 4 to 8 mm size) in the lungs on computed tomography. The hemorrhagic pharyngeal tonsils with hot signals on 18F-fluorodeoxyglucose-positron emission tomography-computed tomography were biopsied revealing the presence of EBV-encoded small nuclear RNA (EBER)-positive cells; however, no lymphoma was noted. The patient was diagnosed as having atypical EBV-infectious mononucleosis associated with primary EBV infection. Pulmonary nodules markedly reduced in numbers and sizes spontaneously over a 2-year period. Differential diagnosis of pulmonary nodules in childhood should include atypical EBV infection.

Mycobacterium abscessus Displays Fitness for Fomite Transmission

PubMed Central

Caceres, Silvia M.; Honda, Jennifer R.; Davidson, Rebecca M.; Epperson, L. Elaine; Strong, Michael; Chan, Edward D.; Nick, Jerry A.

2017-01-01

ABSTRACT Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium (NTM) increasingly reported in soft tissue infections and chronic lung diseases, including cystic fibrosis. The environmental source of M. abscessus has not been definitively identified, but NTM have been detected in soil and water. To determine the potential of soil-derived M. abscessus as an infectious source, we explored the association, growth, and survival of M. abscessus with defined mineral particulates, including kaolin, halloysite, and silicone dioxide, and house dust as possible M. abscessus fomites. M. abscessus physically associated with particulates, and the growth of M. abscessus was enhanced in the presence of both kaolin and house dust. M. abscessus survived desiccation for 2 weeks but was not viable after 3 weeks. The rate of decline of M. abscessus viability during desiccation was reduced in the presence of house dust. The evidence for enhanced growth and survival of M. abscessus during alternating growth and drying periods suggests that dissemination could occur when in wet or dry environments. These studies are important to understand environmental survival and acquisition of NTM. IMPORTANCE The environmental source of pulmonary Mycobacterium abscessus infections is not known. Fomites are nonliving carriers of infectious agents and may contribute to acquisition of M. abscessus. This study provides evidence that M. abscessus growth is enhanced in the presence of particulates, using kaolin, an abundant natural clay mineral, and house dust as experimental fomites. Moreover, M. abscessus survived desiccation for up to 2 weeks in the presence of house dust, kaolin, and several chemically defined mineral particulates; mycobacterial viability during extended periods of dessication was enhanced by the presence of house dust. The growth characteristics of M. abscessus with particulates suggest that a fomite mechanism of transmission may contribute to M. abscessus

Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

PubMed

Yang, Degang; Shui, Tiejun; Miranda, Jake W; Gilson, Danny J; Song, Zhengyu; Chen, Jia; Shi, Chao; Zhu, Jianyu; Yang, Jun; Jing, Zhichun

2016-01-01

The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis.

PubMed

Luciw, Paul A; Oslund, Karen L; Yang, Xiao-Wei; Adamson, Lourdes; Ravindran, Resmi; Canfield, Don R; Tarara, Ross; Hirst, Linda; Christensen, Miles; Lerche, Nicholas W; Offenstein, Heather; Lewinsohn, David; Ventimiglia, Frank; Brignolo, Laurie; Wisner, Erik R; Hyde, Dallas M

2011-11-01

Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of three-dimensional objects from two-dimensional sections and thus is suited to quantify histological lesions. We have developed a protocol for stereological analysis of the lung in rhesus macaques inoculated with a pathogenic clinical strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of infection and tuberculosis similar to that of naturally infected humans. Conditions were optimized for collecting lung samples in a nonbiased, random manner. Bacterial load in these samples was assessed by a standard plating assay, and granulomas were graded and enumerated microscopically. Stereological analysis provided quantitative data that supported a significant correlation between bacterial load and lung granulomas. Thus this stereological approach enables a quantitative, statistically valid analysis of the impact of M. tuberculosis infection in the lung and will serve as an essential tool for objectively comparing the efficacy of drugs and vaccines.

Development of a Gene Expression Assay for the Diagnosis of Mycobacterium bovis Infection in African Lions (Panthera leo).

PubMed

Olivier, T T; Viljoen, I M; Hofmeyr, J; Hausler, G A; Goosen, W J; Tordiffe, A S W; Buss, P; Loxton, A G; Warren, R M; Miller, M A; van Helden, P D; Parsons, S D C

2017-06-01

Mycobacterium bovis infection, the cause of bovine tuberculosis (BTB), is endemic in wildlife in the Kruger National Park (KNP), South Africa. In lions, a high infection prevalence and BTB mortalities have been documented in the KNP; however, the ecological consequences of this disease are currently unknown. Sensitive assays for the detection of this infection in this species are therefore required. Blood from M. bovis-exposed, M. bovis-unexposed, M. tuberculosis-exposed and M. bovis-infected lions was incubated in QuantiFERON ® -TB Gold (QFT) tubes containing either saline or ESAT-6/CFP-10 peptides. Using qPCR, selected reference genes were evaluated for expression stability in these samples and selected target genes were evaluated as markers of antigen-dependent immune activation. The abundance of monokine induced by gamma interferon (MIG/CXCL9) mRNA, measured in relation to that of YWHAZ, was used as a marker of ESAT-6/CFP-10 sensitization. The gene expression assay results were compared between lion groups, and lenient and stringent diagnostic cut-off values were calculated. This CXCL9 gene expression assay combines a highly specific stimulation platform with a sensitive diagnostic marker that allows for discrimination between M. bovis-infected and M. bovis-uninfected lions. © 2015 Blackwell Verlag GmbH.

Investigation of the high rates of extrapulmonary tuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection.

PubMed

Berg, Stefan; Schelling, Esther; Hailu, Elena; Firdessa, Rebuma; Gumi, Balako; Erenso, Girume; Gadisa, Endalamaw; Mengistu, Araya; Habtamu, Meseret; Hussein, Jemal; Kiros, Teklu; Bekele, Shiferaw; Mekonnen, Wondale; Derese, Yohannes; Zinsstag, Jakob; Ameni, Gobena; Gagneux, Sebastien; Robertson, Brian D; Tschopp, Rea; Hewinson, Glyn; Yamuah, Lawrence; Gordon, Stephen V; Aseffa, Abraham

2015-03-03

Ethiopia, a high tuberculosis (TB) burden country, reports one of the highest incidence rates of extra-pulmonary TB dominated by cervical lymphadenitis (TBLN). Infection with Mycobacterium bovis has previously been excluded as the main reason for the high rate of extrapulmonary TB in Ethiopia. Here we examined demographic and clinical characteristics of 953 pulmonary (PTB) and 1198 TBLN patients visiting 11 health facilities in distinct geographic areas of Ethiopia. Clinical characteristics were also correlated with genotypes of the causative agent, Mycobacterium tuberculosis. No major patient or bacterial strain factor could be identified as being responsible for the high rate of TBLN, and there was no association with HIV infection. However, analysis of the demographic data of involved patients showed that having regular and direct contact with live animals was more associated with TBLN than with PTB, although no M. bovis was isolated from patients with TBLN. Among PTB patients, those infected with Lineage 4 reported "contact with other TB patient" more often than patients infected with Lineage 3 did (OR = 1.6, CI 95% 1.0-2.7; p = 0.064). High fever, in contrast to low and moderate fever, was significantly associated with Lineage 4 (OR = 2.3; p = 0.024). On the other hand, TBLN cases infected with Lineage 4 tended to get milder symptoms overall for the constitutional symptoms than those infected with Lineage 3. The study suggests a complex role for multiple interacting factors in the epidemiology of extrapulmonary TB in Ethiopia, including factors that can only be derived from population-based studies, which may prove to be significant for TB control in Ethiopia.

Evaluation of tissue fixation methods to inactivate Mycobacterium bovis under routine laboratory conditions

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis (M. bovis) is the etiological agent of tuberculosis in mammals including humans. The seriousness of disease and low infective dose require that the agent be handled under biosafety level 3 conditions. Many experimental protocols include histological examination of infected tissue...

Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis.

PubMed

Cardona, Pere-Joan; Amat, Isabel; Gordillo, Sergi; Arcos, Virginia; Guirado, Evelyn; Díaz, Jorge; Vilaplana, Cristina; Tapia, Gustavo; Ausina, Vicenç

2005-02-03

Reduction of colony forming units by rifampicin-isoniazid therapy given 9-17 weeks post-infection was made more pronounced by immunotherapy with a vaccine made of fragmented Mycobacterium tuberculosis cells detoxified and liposomed (RUTI), given on weeks 17, 19 and 21 post-infection, in the murine model of tuberculosis in C57BL/6 and DBA/2 inbred strains. RUTI triggered a Th1/Th2 response, as demonstrated by the production of IgG1, IgG2a and IgG3 antibodies against a wide range of peptides. The histological analysis did not show neither eosinophilia nor necrosis, and granulomatous infiltration was only slightly increased in C57BL/6 mice when RUTI was administered intranasally.

Mycobacterium bovis Bacille Calmette-Guérin Infection in the CNS Suppresses Experimental Autoimmune Encephalomyelitis and Th17 Responses in an IFN-gamma-independent Manner1

PubMed Central

Lee, JangEun; Reinke, Emily K.; Zozulya, Alla L.; Sandor, Matyas; Fabry, Zsuzsanna

2009-01-01

Multiple sclerosis (MS) and an animal model resembling MS, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases of the central nervous system (CNS) that are suppressed by systemic mycobacterial infection in mice and BCG vaccination in humans. Host defense responses against Mycobacterium in mice are influenced by T lymphocytes and their cytokine products, particularly IFN-γ, which plays a protective regulatory role in EAE. To analyze the counter-regulatory role of mycobacterial infection-induced IFN-γ in the CNS on the function of the pathological Th17 cells and the clinical outcome of EAE, we induced EAE in mice that were intracerebrally infected with Mycobacterium bovis bacille Calmette-Guerin (BCG). Here we demonstrate that intracerebral (i.c.) BCG infection prevented inflammatory cell recruitment to the spinal cord and suppressed the development of EAE. Concomitantly, there was a significant decrease in the frequency of MOG-specific IFN-γ-producing CD4+ T cells in the CNS. IL-17+CD4+ T cell responses were significantly suppressed in i.c. BCG-infected mice following EAE induction regardless of T cell specificity. The frequency of Foxp3+CD4+ T cells in these mice was equivalent to that of control mice. The i.c. BCG infection-induced protection of EAE and suppression of MOG-specific IL-17+CD4+ T cell responses were similar in both wild type (WT) and IFN-γ deficient mice. These data show that live BCG infection in the brain suppresses CNS autoimmunity. These findings also reveal that the regulation of Th17-mediated autoimmunity in the CNS can be independent of IFN-γ-mediated mechanisms. PMID:18941210

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity*

PubMed Central

Richard-Greenblatt, Melissa; Bach, Horacio; Adamson, John; Peña-Diaz, Sandra; Li, Wu; Steyn, Adrie J. C.; Av-Gay, Yossef

2015-01-01

Ergothioneine (EGT) is synthesized in mycobacteria, but limited knowledge exists regarding its synthesis, physiological role, and regulation. We have identified Rv3701c from Mycobacterium tuberculosis to encode for EgtD, a required histidine methyltransferase that catalyzes first biosynthesis step in EGT biosynthesis. EgtD was found to be phosphorylated by the serine/threonine protein kinase PknD. PknD phosphorylates EgtD both in vitro and in a cell-based system on Thr213. The phosphomimetic (T213E) but not the phosphoablative (T213A) mutant of EgtD failed to restore EGT synthesis in a ΔegtD mutant. The findings together with observed elevated levels of EGT in a pknD transposon mutant during in vitro growth suggests that EgtD phosphorylation by PknD negatively regulates EGT biosynthesis. We further showed that EGT is required in a nutrient-starved model of persistence and is needed for long term infection of murine macrophages. PMID:26229105

MYCOBACTERIUM AVIUM AND DRINKING WATER WHAT ARE THE CONNECTIONS?

EPA Science Inventory

Background: Human Mycobacterium avium infections are only known to be acquired from environmental sources such as water and soil. We compared M. avium isolates from clinical and drinking water sources using molecular tools. Methods: M. avium was isolated from water samples colle...

Unexpected Role for IL-17 in Protective Immunity against Hypervirulent Mycobacterium tuberculosis HN878 Infection

PubMed Central

Gopal, Radha; Monin, Leticia; Slight, Samantha; Uche, Uzodinma; Blanchard, Emmeline; A. Fallert Junecko, Beth; Ramos-Payan, Rosalio; Stallings, Christina L.; Reinhart, Todd A.; Kolls, Jay K.; Kaushal, Deepak; Nagarajan, Uma; Rangel-Moreno, Javier; Khader, Shabaana A.

2014-01-01

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one third of the world's population. Among these infections, clinical isolates belonging to the W-Beijing appear to be emerging, representing about 50% of Mtb isolates in East Asia, and about 13% of all Mtb isolates worldwide. In animal models, infection with W-Beijing strain, Mtb HN878, is considered “hypervirulent” as it results in increased mortality and causes exacerbated immunopathology in infected animals. We had previously shown the Interleukin (IL) -17 pathway is dispensable for primary immunity against infection with the lab adapted Mtb H37Rv strain. However, it is not known whether IL-17 has any role to play in protective immunity against infection with clinical Mtb isolates. We report here that lab adapted Mtb strains, such as H37Rv, or less virulent Mtb clinical isolates, such as Mtb CDC1551, do not require IL-17 for protective immunity against infection while infection with Mtb HN878 requires IL-17 for early protective immunity. Unexpectedly, Mtb HN878 induces robust production of IL-1β through a TLR-2-dependent mechanism, which supports potent IL-17 responses. We also show that the role for IL-17 in mediating protective immunity against Mtb HN878 is through IL-17 Receptor signaling in non-hematopoietic cells, mediating the induction of the chemokine, CXCL-13, which is required for localization of T cells within lung lymphoid follicles. Correct T cell localization within lymphoid follicles in the lung is required for maximal macrophage activation and Mtb control. Since IL-17 has a critical role in vaccine-induced immunity against TB, our results have far reaching implications for the design of vaccines and therapies to prevent and treat emerging Mtb strains. In addition, our data changes the existing paradigm that IL-17 is dispensable for primary immunity against Mtb infection, and instead suggests a differential role for IL-17 in early protective immunity against

Crystal Structure of a UDP-glucose-specific Glycosyltransferase from a Mycobacterium Species

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

Fulton, Zara; McAlister, Adrian; Wilce, Matthew C.J.

2008-10-24

Glycosyltransferases (GTs) are a large and ubiquitous family of enzymes that specifically transfer sugar moieties to a range of substrates. Mycobacterium tuberculosis contains a large number of GTs, many of which are implicated in cell wall synthesis, yet the majority of these GTs remain poorly characterized. Here, we report the high resolution crystal structures of an essential GT (MAP2569c) from Mycobacterium avium subsp. paratuberculosis (a close homologue of Rv1208 from M. tuberculosis) in its apo- and ligand-bound forms. The structure adopted the GT-A fold and possessed the characteristic DXD motif that coordinated an Mn{sup 2+} ion. Atypical of most GTsmore » characterized to date, MAP2569c exhibited specificity toward the donor substrate, UDP-glucose. The structure of this ligated complex revealed an induced fit binding mechanism and provided a basis for this unique specificity. Collectively, the structural features suggested that MAP2569c may adopt a 'retaining' enzymatic mechanism, which has implications for the classification of other GTs in this large superfamily.« less

Susceptibility of Mycobacterium avium sbsp paratuberculosis to monensin sodium or tilmicosin phosphate in vitro and resulting infectivity in a murine model.

PubMed

Brumbaugh, Gordon W; Simpson, R Bruce; Edwards, John F; Anders, Dwayne R; Thomson, T D

2004-07-01

This study was designed to determine the susceptibility in vitro and infectivity of 1 field isolate of Mycobacterium avium sbsp paratuberculosis after exposure to monensin sodium and tilmicosin phosphate. Minimum inhibitory concentrations (0.39 microg monensin sodium/mL; 1.60 microg tilmicosin phosphate/mL) were determined in quintuplicate. Organisms were then incubated with 3 different concentrations of each medication for 3 different lengths of time, then washed and resuspended in sterile physiologic saline and injected intraperitoneally into mice that were genetically susceptible to infection. Mice were euthanatized 50 d later and the number of hepatic granulomas was used as the indicator of infectivity. Neither time of incubation nor concentration of medication had any effect on the infectivity of the organisms. Monensin sodium significantly reduced the number of hepatic granulomas in genetically susceptible mice while tilmicosin phosphate did not. Antimycobacterial activity of monensin sodium suggests that the role of monensin in the control of bovine paratuberculosis should be evaluated further.

Susceptibility of Mycobacterium avium sbsp paratuberculosis to monensin sodium or tilmicosin phosphate in vitro and resulting infectivity in a murine model

PubMed Central

2004-01-01

Abstract This study was designed to determine the susceptibility in vitro and infectivity of 1 field isolate of Mycobacterium avium sbsp paratuberculosis after exposure to monensin sodium and tilmicosin phosphate. Minimum inhibitory concentrations (0.39 μg monensin sodium/mL; 1.60 μg tilmicosin phosphate/mL) were determined in quintuplicate. Organisms were then incubated with 3 different concentrations of each medication for 3 different lengths of time, then washed and resuspended in sterile physiologic saline and injected intraperitoneally into mice that were genetically susceptible to infection. Mice were euthanatized 50 d later and the number of hepatic granulomas was used as the indicator of infectivity. Neither time of incubation nor concentration of medication had any effect on the infectivity of the organisms. Monensin sodium significantly reduced the number of hepatic granulomas in genetically susceptible mice while tilmicosin phosphate did not. Antimycobacterial activity of monensin sodium suggests that the role of monensin in the control of bovine paratuberculosis should be evaluated further. PMID:15352541

Molecular characteristics of "Mycobacterium canettii" the smooth Mycobacterium tuberculosis bacilli.

PubMed

Fabre, Michel; Hauck, Yolande; Soler, Charles; Koeck, Jean-Louis; van Ingen, Jakko; van Soolingen, Dick; Vergnaud, Gilles; Pourcel, Christine

2010-12-01

Since the first discovery of the smooth tubercle (SmTB) bacilli "Mycobacterium canettii" less than 60 isolates have been reported, all but one originating from a limited geographical location, the Horn of Africa. In spite of its rarity, the SmTB lineage deserves special attention. Previous investigations suggested that SmTB isolates represent an ancestral lineage of the Mycobacterium tuberculosis complex (MTBC) and that consequently they might provide essential clues on the origin and evolution of the MTBC. There is evidence that unlike the rest of the MTBC, SmTB strains recombine chromosomal sequences with a yet unknown Mycobacterium species. This behavior contributes to the much larger genetic heterogeneity observed in the SmTB isolates compared to the other members of the MTBC. We have collected 59 SmTB isolates of which 14 were newly recovered since previous reports, and performed extensive phenotypical and genotypical characterization. We take advantage of these investigations to review the current knowledge of "M. canettii". Their characteristics and the apparent lack of human to human transmission are consistent with the previously proposed existence of non-human sources of infection. SmTB strains show remarkably common features together with secondary and taxonomically minor genetic differences such as the presence or absence of the CRISPR (Clustered Regularly Interspersed Palindromic Repeat) locus (usually called Direct Repeat or DR region) or number of IS sequences. Multiple Locus Variable number of tandem repeat Analysis (MLVA) and DR region analyses reveal one predominant clone, one minor clone and a number of more distantly related strains. This suggests that the two most frequent clones may represent successfully emerging lineages. Copyright © 2010 Elsevier B.V. All rights reserved.

Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and Their Microparticles.

PubMed

Hare, Nathan J; Lee, Ling Y; Loke, Ian; Britton, Warwick J; Saunders, Bernadette M; Thaysen-Andersen, Morten

2017-01-06

Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of frontline alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M. tb infection. Infection promoted a dramatic regulation of the macrophage proteome. Most notably, significant infection-dependent down-regulation (4-26 fold) of 11 lysosomal exoglycosidases, e.g., β-galactosidase, β-hexosaminidases and α-/β-mannosidases, was observed. Relative weak infection-driven transcriptional regulation of these exoglycosidases and a stronger augmentation of the extracellular hexosaminidase activity demonstrated that the lysosome-centric changes may originate predominantly from infection-induced secretion of the lysosomal content. The macrophages showed heterogeneous N-glycan profiles and displayed significant up-regulation of complex-type glycosylation and concomitant down-regulation of paucimannosylation upon infection. Complementary intact N-glycopeptide analysis supported a subcellular-specific manipulation of the glycosylation machinery and altered glycosylation patterns of lysosomal N-glycoproteins within infected macrophages. Interestingly, the corresponding macrophage-derived MPs displayed unique N-glycome and proteome signatures supporting a preferential packaging from plasma membranes. The MPs were devoid of infection-dependent N-glycosylation signatures, but interestingly displayed increased levels of the glyco-initiating oligosaccharyltransferase complex and associated α-glucosidases that correlated with increased formation, N-glycan precursor levels

Impact of pe_pgrs33 Gene Polymorphisms on Mycobacterium tuberculosis Infection and Pathogenesis.

PubMed

Camassa, Serena; Palucci, Ivana; Iantomasi, Raffaella; Cubeddu, Tiziana; Minerva, Mariachiara; De Maio, Flavio; Jouny, Samuel; Petruccioli, Elisa; Goletti, Delia; Ria, Francesco; Sali, Michela; Sanguinetti, Maurizio; Manganelli, Riccardo; Rocca, Stefano; Brodin, Priscille; Delogu, Giovanni

2017-01-01

PE_PGRS33 is a surface-exposed protein of Mycobacterium tuberculosis ( Mtb ) which exerts its role in macrophages entry and immunomodulation. In this study, we aimed to investigate the polymorphisms in the pe_pgrs33 gene of Mtb clinical isolates and evaluate their impact on protein functions. We sequenced pe_pgrs33 in a collection of 135 clinical strains, genotyped by 15-loci MIRU-VNTR and spoligotyping and belonging to the Mtb complex (MTBC). Overall, an association between pe_pgrs33 alleles and MTBC genotypes was observed and a dN/dS ratio of 0.64 was obtained, suggesting that a purifying selective pressure is acting on pe_pgrs33 against deleterious SNPs. Among a total of 19 pe_pgrs33 alleles identified in this study, 5 were cloned and used to complement the pe_pgrs33 knock-out mutant strain of Mtb H37Rv ( Mtb Δ33) to assess the functional impact of the respective polymorphisms in in vitro infections of primary macrophages. In human monocyte-derived macrophages (MDMs) infection, large in-frame and frameshift mutations were unable to restore the phenotype of Mtb H37Rv, impairing the cell entry capacity of Mtb , but neither its intracellular replication rate nor its immunomodulatory properties. In vivo studies performed in the murine model of tuberculosis (TB) demonstrated that the Mtb Δ33 mutant strain was not impaired in the ability to infect and replicate in the lung tissue compared to the parental strain. Interestingly, Mtb Δ33 showed an enhanced virulence during the chronic steps of infection compared to Mtb H37Rv. Similarly, the complementation of Mtb Δ33 with a frameshift allele also resulted in a Mtb strain capable of causing a surprisingly enhanced tissue damage in murine lungs, during the chronic steps of infection. Together, these results further support the role of PE_PGRS33 in the pathogenesis and virulence of Mtb .

Nodular skin reactions in eyebrow permanent makeup: two case reports and an infection by Mycobacterium haemophilum.

PubMed

Wollina, Uwe

2011-09-01

Permanent makeup is becoming more and more popular. The procedures, however, bear some medical risks. We will describe possible adverse effects of the procedure. This is a report of clinical observations. We report about two women aged 26 and 47 years, who developed nodules with some delay after permanent tattooing the eyebrows. Clinical, histologic, and laboratory investigations revealed a noninfectious granulomatous reaction not responding to topical calcineurin inhibitor but corticosteroids in the younger patient. In the other woman, an infection by Mycobacterium haemophilum could be identified. A triple combination of clarithromycin, ciprofloxacin, and rifampicin succeeded in clearance of the lesions. Adverse reactions after permanent makeup need a medical evaluation to identify health risks and initiate early treatment. © 2011 Wiley Periodicals, Inc.

Pathology and diagnosis of Mycobacterium bovis in naturally infected dromedary camels (Camelus dromedarius) in India.

PubMed

Narnaware, Shirish Dadarao; Dahiya, Shyam Singh; Tuteja, Fateh Chand; Nagarajan, Govindasamy; Nath, Kashi; Patil, Nitin Vasantrao

2015-12-01

The present study investigated the pathological features of tuberculosis (TB) caused by Mycobacterium bovis and its diagnosis in naturally infected dromedary camels from an organized farm in India. During the period of the 5-year study, a total of 18 (19.56 %) camels out of 92 examined showed gross lesions compatible with TB at post-mortem. The clinical signs and pathological lesions in these camels were studied, and the efficacy of different diagnostic tests was also assessed. On the basis of occurrence and distribution of gross TB lesions, the infected camels revealed two different lesional patterns as pulmonary (n = 15) and disseminated (n = 3) form. The histopathology of affected organs revealed typical granulomatous lesions wherein the giant cells and acid-fast bacilli were occasionally observed in pulmonary form whereas they frequently observed in disseminated form. The single intradermal tuberculin test (SIDT) detected TB in 10 (55.55 %) whereas the Ziehl-Neelsen (ZN) stain and IS6110 PCR from tissue lesions detected 13 (72.22 %) and 18 (100 %) of the infected camels, respectively. The study suggests that pulmonary form of the TB is more common in camels indicating respiratory route as the major source of exposure in camel herds. Moreover, very low sensitivity of SIDT was observed which highlights the difficulty for confirmation of TB in live camels.

HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

PubMed

Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

2017-09-15

Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles

PubMed Central

Lee, Bai-Yu; Xue, Min; Thomas, Courtney R.; Meng, Huan; Ferris, Daniel; Nel, Andre E.; Zink, Jeffrey I.

2012-01-01

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by Mycobacterium tuberculosis, thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into M. tuberculosis-infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against M. tuberculosis-infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill M. tuberculosis within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis. PMID:22354311

Respiratory infections due to nontuberculous mycobacterias.

PubMed

Máiz Carro, Luis; Barbero Herranz, Esther; Nieto Royo, Rosa

2018-03-09

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis

PubMed Central

Hempel, Randy J.; Bannantine, John P.

2016-01-01

Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advanced clinical stage of infection, are poorly understood. This study examines gene expression in the ileocecal valve (ICV) of Holstein dairy cows at different stages of MAP infection. The ICV is known to be a primary site of MAP colonization and provides an ideal location to identify genes that are relevant to the progression of this disease. RNA was prepared from ICV tissues and RNA-Seq was used to compare gene transcription between clinical, subclinical, and uninfected control animals. Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes. Results demonstrated that many of the pathways that had strong differential gene expression between uninfected control and clinical cows were related to the immune system, such as the T- and B-cell receptor signaling, apoptosis, NOD-like receptor signaling, and leukocyte transendothelial migration pathways. In contrast, the comparison of gene transcription between control and subclinical cows identified pathways that were primarily involved in metabolism. The results from the comparison between clinical and subclinical animals indicate recruitment of neutrophils, up regulation of lysosomal peptidases, increase in immune cell transendothelial migration, and modifications of the extracelluar matrix. This study provides important insight into how cattle respond to a natural MAP infection at the gene transcription level within a key target tissue for infection. PMID:27093613

Experimental Model of Tuberculosis in the Domestic Goat after Endobronchial Infection with Mycobacterium caprae ▿

PubMed Central

Pérez de Val, Bernat; López-Soria, Sergio; Nofrarías, Miquel; Martín, Maite; Vordermeier, H. Martin; Villarreal-Ramos, Bernardo; Romera, Nadine; Escobar, Manel; Solanes, David; Cardona, Pere-Joan; Domingo, Mariano

2011-01-01

Caprine tuberculosis (TB) has increased in recent years, highlighting the need to address the problem the infection poses in goats. Moreover, goats may represent a cheaper alternative for testing of prototype vaccines in large ruminants and humans. With this aim, a Mycobacterium caprae infection model has been developed in goats. Eleven 6-month-old goats were infected by the endobronchial route with 1.5 × 103 CFU, and two other goats were kept as noninfected controls. The animals were monitored for clinical and immunological parameters throughout the experiment. After 14 weeks, the goats were euthanized, and detailed postmortem analysis of lung lesions was performed by multidetector computed tomography (MDCT) and direct observation. The respiratory lymph nodes were also evaluated and cultured for bacteriological analysis. All infected animals were positive in a single intradermal comparative cervical tuberculin (SICCT) test at 12 weeks postinfection (p.i.). Gamma interferon (IFN-γ) antigen-specific responses were detected from 4 weeks p.i. until the end of the experiment. The humoral response to MPB83 was especially strong at 14 weeks p.i. (13 days after SICCT boost). All infected animals presented severe TB lesions in the lungs and associated lymph nodes. M. caprae was recovered from pulmonary lymph nodes in all inoculated goats. MDCT allowed a precise quantitative measure of TB lesions. Lesions in goats induced by M. caprae appeared to be more severe than those induced in cattle by M. bovis over a similar period of time. The present work proposes a reliable new experimental animal model for a better understanding of caprine tuberculosis and future development of vaccine trials in this and other species. PMID:21880849

Metabolic profiling of lung granuloma in Mycobacterium tuberculosis infected guinea pigs: ex vivo 1H magic angle spinning NMR studies.

PubMed

Somashekar, B S; Amin, Anita G; Rithner, Christopher D; Troudt, JoLynn; Basaraba, Randall; Izzo, Angelo; Crick, Dean C; Chatterjee, Delphi

2011-09-02

A crucial and distinctive feature of tuberculosis infection is that Mycobacterium tuberculosis (Mtb) resides in granulomatous lesion at various stages of disease development and necrosis, an aspect that is little understood. We used a novel approach, applying high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HRMAS NMR) directly to infected tissues, allowing us to study the development of tuberculosis granulomas in guinea pigs in an untargeted manner. Significant up-regulation of lactate, alanine, acetate, glutamate, oxidized and the reduced form of glutathione, aspartate, creatine, phosphocholine, glycerophosphocholine, betaine, trimethylamine N-oxide, myo-inositol, scyllo-inositol, and dihydroxyacetone was clearly visualized and was identified as the infection progressed. Concomitantly, phosphatidylcholine was down-regulated. Principal component analysis of NMR data revealed clear group separation between infected and uninfected tissues. These metabolites are suggestive of utilization of alternate energy sources by the infiltrating cells that generate much of the metabolites in the increasingly necrotic and hypoxic developing granuloma through the glycolytic, pentose phosphate, and tricarboxylic acid pathways. The most relevant changes seen are, surprisingly, very similar to metabolic changes seen in cancer during tumor development.

Mycobacterium chimaera and cardiac surgery.

PubMed

Stewardson, Andrew J; Stuart, Rhonda L; Cheng, Allen C; Johnson, Paul Dr

2017-02-20

There is an ongoing investigation into infections with non-tuberculous mycobacteria associated with contaminated heater-cooler units used in cardiac surgery. The overall risk is low, but surgical site and disseminated infections have been reported, including one possible case in Australia, mainly with surgery involving implantation of prosthetic material. Mycobacterium chimaera infection should be considered in patients who have previously undergone surgery with cardiopulmonary bypass and who present with cardiac or disseminated infection or sternal wound infection unresponsive to standard antibiotic therapy. Where cases are suspected, patients should be investigated and managed in consultation with an infectious diseases physician and/or clinical microbiologist. If cases are confirmed or heater-cooler devices are found to be contaminated, details should be reported to the hospital infection control team, the jurisdictional health department, the Therapeutic Goods Administration and the Australian distributor of the affected heater-cooler unit(s). Measures to manage risk should include communicating with relevant hospital departments, ensuring that the manufacturer's updated instructions for use are followed, regular testing of machines, and reviewing the location of machines when in use.

Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae*

PubMed Central

Medeiros, Rychelle Clayde Affonso; Girardi, Karina do Carmo de Vasconcelos; Cardoso, Fernanda Karlla Luz; Mietto, Bruno de Siqueira; Pinto, Thiago Gomes de Toledo; Gomez, Lilian Sales; Rodrigues, Luciana Silva; Gandini, Mariana; Amaral, Julio Jablonski; Antunes, Sérgio Luiz Gomes; Corte-Real, Suzana; Rosa, Patricia Sammarco; Pessolani, Maria Cristina Vidal; Nery, José Augusto da Costa; Sarno, Euzenir Nunes; Batista-Silva, Leonardo Ribeiro; Sola-Penna, Mauro; Oliveira, Marcus Fernandes; Moraes, Milton Ozório; Lara, Flavio Alves

2016-01-01

Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. PMID:27555322

Identification of new antigen candidates for the early diagnosis of Mycobacterium avium subsp. paratuberculosis infection in goats.

PubMed

Souriau, Armel; Freret, Sandrine; Foret, Benjamin; Willemsen, Peter T J; Bakker, Douwe; Guilloteau, Laurence A

2017-12-01

Currently Mycobacterium avium subsp. paratuberculosis (MAP) infection is diagnosed through indirect tests based on the immune response induced by the infection. The antigens commonly used in IFN-γ release assays (IGRA) are purified protein derivative tuberculins (PPD). However, PPDs, lack both specificity (Sp) and sensitivity (Se) in the early phase of infection. This study investigated the potential of 16 MAP recombinant proteins and five lipids to elicit the release of IFN-γ in goats from herds with or without a history of paratuberculosis. Ten recombinant proteins were selected as potential candidates for the detection of MAP infection in young goats. They were found to detect 25 to 75% of infected shedder (IS) and infected non-shedder (INS) kids younger than 10months of age. In comparison, PPD was shown to detect only 10% of INS and no IS kids. For seven antigens, Se (21-33%) and Sp (≥90%) of IGRA were shown to be comparable with PPD at 20months old. Only three antigens were suitable candidates to detect IS adult goats, although Se was lower than that obtained with PPD. In paratuberculosis-free herds, IGRA results were negative in 97% of indoor goats and 86% of outdoor goats using the 10 antigens. However, 22 to 44% of one-year-old outdoor goats were positive suggesting that they may be infected. In conclusion, this study showed that ten MAP recombinant proteins are potential candidates for early detection of MAP infected goats. Combining these antigens could form a possible set of MAP antigens to optimize the Se of caprine IGRA. Copyright © 2017 Elsevier Ltd. All rights reserved.

A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

PubMed

Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

2015-12-01

Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

Polymorphisms of twenty regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans or animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and the other members o...

Helicobacter infections with rare bacteria or minimal gastritis: Expecting the unexpected.

PubMed

Glickman, Jonathan N; Noffsinger, Amy; Nevin, Daniel T; Ray, Mukunda; Lash, Richard H; Genta, Robert M

2015-07-01

The routine use of special stains for detection of Helicobacter remains controversial. To determine the frequency of histologically atypical Helicobacter infection. All gastric biopsies received at a large pathology reference laboratory over a 6-month period were stained for Helicobacter, and the histologic and clinicopathologic parameters evaluated. Amongst 7663 Helicobacter-positive biopsies, 823 (10.7%) did not show typical chronic active gastritis with numerous Helicobacter organisms, and were therefore considered histologically atypical. Rare Helicobacter pylori organisms accounted for 58.0% of all atypical infections; the next most common atypical Helicobacter infection was that with minimal or no gastric inflammation (23.3% of atypical infections). Patients in these groups did not differ demographically from those with other forms of atypical or typical Helicobacter infection, although a small subgroup (6%) was more likely to have had a previously treated infection. In many of these atypical infections, Helicobacter would not have been suspected based on the histologic findings alone, and would have been missed without routine special stains. Performing a sensitive stain could prevent additional testing and allow prompt treatment of the affected patients, thus substantially reducing the risk for peptic ulcer and gastric cancer and preventing the transmission of the infection to family members. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Mycobacterium bovis infection of cattle and white-tailed deer: Translational research of relevance to human tuberculosis

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB) is a premier example of a disease complex with pathogens primarily affecting humans (i.e., Mycobacterium tuberculosis) or livestock and wildlife (i.e., Mycobacterium bovis) and with a long history of inclusive collaborations between physicians and veterinarians. Advances with the s...

Allium sativum Constituents Exhibit Anti-tubercular Activity In vitro and in RAW 264.7 Mouse Macrophage Cells Infected with Mycobacterium tuberculosis H37Rv

PubMed Central

Nair, Swapna S.; Gaikwad, Sujay S.; Kulkarni, Savita P.; Mukne, Alka Pravin

2017-01-01

Background: Long duration of treatment, side-effects of currently used anti-tubercular drugs and emergence of drug-resistant forms of Mycobacterium tuberculosis (MTB) warrants the need to develop new drugs to tackle the scourge of tuberculosis (TB). Garlic is an edible plant reported to have anti-tubercular activity. However, previous researches on anti-tubercular effect of garlic were focused mostly on preliminary in vitro screening. Objective: To identify constituents responsible for anti-tubercular activity of thiosulfinate-derivative rich extract of garlic (GE) and to evaluate activity of the most active constituent in RAW 264.7 mouse macrophage cells infected with M. tuberculosis H37Rv (MTBH). Materials and Methods: In the present study, we have isolated eight compounds from GE by flash chromatography. The isolated compounds were characterized by 1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry and Fourier transform infrared spectroscopy. Individual isolates and GE were screened for activity against MTBH by Resazurin Microtitre Plate Assay (REMA). Results: Anti-tubercular activity of GE was superior to that of isolates when evaluated by REMA, possibly due to synergism amongst the constituents of GE. Cytotoxicity of GE was evaluated in RAW 264.7 mouse macrophage cells and it was observed that GE had a favorable selectivity index (>10). Therefore, anti-tubercular activity of GE was further evaluated by intracellular macrophage infection model. GE demonstrated concentration-dependent activity in macrophages infected with MTBH. Conclusion: This is the first report on intracellular anti-tubercular activity of any extract of garlic or its components. Appreciable intracellular anti-tubercular activity of GE in macrophages combined with low cytotoxicity makes it a suitable candidate for further development as an anti-tubercular agent. SUMMARY Thiosulfinate-derivative rich extract of Allium sativum showed better activity than its

Efficacy of oral BCG vaccination in protecting free-ranging cattle from natural infection by Mycobacterium bovis.

PubMed

Nugent, Graham; Yockney, Ivor J; Whitford, Jackie; Aldwell, Frank E; Buddle, Bryce M

2017-09-01

Vaccination of cattle against bovine tuberculosis could be a valuable control strategy, particularly in countries faced with intractable ongoing infection from a disease reservoir in wildlife. A field vaccination trial was undertaken in New Zealand. The trial included 1286 effectively free-ranging cattle stocked at low densities in a remote 7600ha area, with 55% of them vaccinated using Mycobacterium bovis BCG (Danish strain 1311). Vaccine was administered orally in all but 34 cases (where it was injected). After inclusion, cattle were exposed to natural sources of M. bovis infection in cattle and wildlife, most notably the brushtail possum (Trichosurus vulpecula). Cattle were slaughtered at 3-5 years of age and were inspected for tuberculous lesions, with mycobacteriological culture of key tissues from almost all animals. The prevalence of M. bovis infection was 4.8% among oral BCG vaccinates, significantly lower than the 11.9% in non-vaccinates. Vaccination appeared to both reduce the incidence of detectable infection, and to slow disease progression. Based on apparent annual incidence, the protective efficacy of oral BCG vaccine was 67.4% for preventing infection, and was higher in cattle slaughtered soon after vaccination. Skin-test reactivity to tuberculin was high in vaccinates re-tested 70days after vaccination but not in non-vaccinates, although reactor animals had minimal response in gamma-interferon blood tests. In re- tests conducted more than 12 months after vaccination, skin-test reactivity among vaccinates was much lower. These results indicate that oral BCG vaccination could be an effective tool for greatly reducing detectable infection in cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy

PubMed Central

Miranda, Jake W.; Gilson, Danny J.; Song, Zhengyu; Chen, Jia; Shi, Chao; Zhu, Jianyu; Yang, Jun; Jing, Zhichun

2016-01-01

Background The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Methodology/Principal Findings Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Conclusions/Significance Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity. PMID:26751388

Brucella melitensis and Mycobacterium tuberculosis depict overlapping gene expression patterns induced in infected THP-1 macrophages.

PubMed

Masoudian, M; Derakhshandeh, A; Ghahramani Seno, M M

2015-01-01

Pathogens infecting mammalian cells have developed various strategies to suppress and evade their hosts' defensive mechanisms. In this line, the intracellular bacteria that are able to survive and propagate within their host cells must have developed strategies to avert their host's killing attitude. Studying the interface of host-pathogen confrontation can provide valuable information for defining therapeutic approaches. Brucellosis, caused by the Brucella strains, is a zoonotic bacterial disease that affects thousands of humans and animals around the world inflicting discomfort and huge economic losses. Similar to many other intracellular dwelling bacteria, infections caused by Brucella are difficult to treat, and hence any attempt at identifying new and common therapeutic targets would prove beneficial for the purpose of curing infections caused by the intracellular bacteria. In THP-1 macrophage infected with Brucella melitensis we studied the expression levels of four host's genes, i.e. EMP2, ST8SIA4, HCP5 and FRMD5 known to be involved in pathogenesis of Mycobacterium tuberculosis. Our data showed that at this molecular level, except for FRMD5 that was downregulated, the other three genes were upregulated by B. melitensis. Brucella melitensis and M. tuberculosis go through similar intracellular processes and interestingly two of the investigated genes, i.e. EMP2 and ST4SIA8 were upregulated in THP-1 cell infected with B. melitensis similar to that reported for THP-1 cells infected with M. tuberculosis. At the host-pathogen interaction interface, this study depicts overlapping changes for different bacteria with common survival strategies; a fact that implies designing therapeutic approaches based on common targets may be possible.

Sensitivity of Mycobacterium bovis to common beef processing interventions

USDA-ARS?s Scientific Manuscript database

Objective. Mycobacterium bovis is the causative agent of bovine tuberculosis, a relevant zoonosis that can spread to humans through inhalation or by ingestion. M. bovis multiplies slowly, so infected animals may be sent to slaughter during the early stages of the disease before diagnosis and when ...

Infectious mononucleosis with atypical manifestations accompanied by transient IgM antibody response for cytomegalovirus.

PubMed

Nishikawa, Jun; Funada, Hisashi; Miyazaki, Takako; Fujinami, Haruka; Miyazono, Takayoshi; Murakami, Jun; Kudo, Takahiko; Sugiyama, Toshiro

2011-10-01

Infectious mononucleosis (IM) is a clinical syndrome caused by primary infection with Epstein-Barr virus (EBV) that is common in adolescents. In adults, particularly in elderly people, the clinical picture of IM tends to be atypical, often leading to a diagnostic challenge. Diagnosis is also complicated because infection with EBV can induce the synthesis of cross-reacting immunoglobulin M antibodies for other herpesviruses. We report an unusual case of infectious mononucleosis in a 34-year-old immunocompetent adult. Epidemiological studies indicate that the average age of primary EBV infection in developed countries is increasing. IM with atypical presentation will be a diagnostic challenge in the future as the number of EBV-naïve adults increases.

Peritoneal Dialysis-Related Peritonitis: Atypical and Resistant Organisms.

PubMed

Cho, Yeoungjee; Struijk, Dirk Gijsbert

2017-01-01

Peritoneal dialysis (PD)-related peritonitis remains to be one of the most frequent and serious complications of PD. In this study, existing literature has been reviewed on PD peritonitis caused by atypical organisms and antibiotic resistant organisms and their impact on patient outcomes. Although uncommon, delay in recognition of PD peritonitis caused by atypical organisms can lead to poor patient outcomes if there is a delay in diagnosis and implementation of appropriate treatment. There is also a large difference in prevalence of antibiotic-resistant infections across the world with variable impact on reported patient-level outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the results of Mycobacterium tuberculosis direct test (MTD) and Mycobacterial culture in urine samples

PubMed Central

Sener, Asli Gamze; Kurultay, Nukhet; Afsar, Ilhan

2008-01-01

Tuberculosis remains a public health problem in Turkey. Rapid detection of Mycobacterium tuberculosis plays a key role in control of infection. In this article, the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) was evaluated for detection of M. tuberculosis in urine samples. The performance of the MTD was very good and appropriate for routine laboratory diagnosis. PMID:24031287

Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge.

PubMed

Bolis, Vasileios; Karadedos, Christos; Chiotis, Ioannis; Chaliasos, Nikolaos; Tsabouri, Sophia

2016-01-01

Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein-Barr virus infection. Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation." Epstein-Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein-Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein-Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Interleukin-12 Therapy Reduces the Number of Immune Cells and Pathology in Lungs of Mice Infected with Mycobacterium tuberculosis

PubMed Central

Nolt, Dawn; Flynn, JoAnne L.

2004-01-01

Alternate modalities for the treatment of Mycobacterium tuberculosis are needed due to the rise in numbers of immunosuppressed individuals at risk for serious disease and the increasing prevalence of multidrug-resistant isolates. Interleukin-12 (IL-12) has been shown to improve immune responses against M. tuberculosis infection in both humans and mice. Previous studies using high-dose IL-12 in various disease models reported a paradoxical immunosuppression. We demonstrate here that exogenous administration of IL-12 for 8 weeks after an aerosolized low dose of M. tuberculosis results in increased survival and decreased pulmonary bacterial loads for CD4-T-cell-deficient mice, most likely due to an early increase in gamma interferon. IL-12 treatment did not impair or enhance the ability of the wild-type mice to control infection, as measured by bacterial numbers. Two novel findings are reported here regarding exogenous IL-12 therapy for M. tuberculosis infections: (i) IL-12 treatment resulted in decreased numbers of immune cells and reduced frequencies of lymphocytes (CD8+, CD4+, and NK cells) in the lungs of infected mice and (ii) IL-12 therapy reduced the pathology of M. tuberculosis-infected lungs, as granulomas were smaller and less numerous. These studies support an immunoregulatory role for IL-12 in tuberculosis. PMID:15102810

Effect of the bradykinin 1 receptor antagonist SSR240612 after oral administration in Mycobacterium tuberculosis-infected mice.

PubMed

Rodrigues-Junior, Valnês S; Pail, Priscilla B; Villela, Anne D; Falcão, Virgínia C A; Dadda, Adílio S; Abbadi, Bruno L; Pesquero, João B; Santos, Diógenes S; Basso, Luiz A; Campos, Maria M

2018-03-01

The role, if any, played by the kinin system in tuberculosis infection models, either in vivo or in vitro, was investigated. The effects of Mycobacterium tuberculosis infection on C57BL/6 wild type, B 1 R-/-, B 2 R-/- and double B 1 R/B 2 R knockout mice were evaluated. Immunohistochemistry analysis was carried out to assess B 1 R and B 2 R expression in spleens and lungs of M. tuberculosis-infected mice. In addition, in vitro experiments with M. tuberculosis-infected macrophages were performed. The in vivo effects of HOE-140 and SSR240612 on the mice model of infection were also evaluated. Infected B 2 R-/- mice exhibited increased splenomegaly, whereas decreased spleen weight in infected double B 1 R/B 2 R knockout mice was observed. The bacterial load, determined as colony-forming units, did not differ in the spleens and lungs of the studied mouse strains. Importantly, immunohistochemical analysis revealed that B 1 R was upregulated in both spleens and lungs of infected mice. M. tuberculosis-infected macrophages incubated with SSR240612, alone or in combination with des-Arg 9 -BK, for four days, displayed a marked inhibitory effect on CFU counts. However, the pre-incubation of the selective B 1 R (des-Arg 9 -BK and SSR240612) and B 2 R (BK and HOE-140) agonists and antagonists, respectively, did not significantly affect the bacterial loads. A statistically significant reduction in the CFU of M. tuberculosis in lungs and spleens of animals treated with SSR240612, but not with HOE-140, was observed. Further efforts should be pursued to clarify whether or not SSR240612 might be considered an option for the treatment of tuberculosis. Copyright © 2018. Published by Elsevier Ltd.

Natural history of Mycobacterium fortuitum pulmonary infection presenting with migratory infiltrates: a case report with microbiological analysis.

PubMed

Okamori, Satoshi; Asakura, Takanori; Nishimura, Tomoyasu; Tamizu, Eiko; Ishii, Makoto; Yoshida, Mitsunori; Fukano, Hanako; Hayashi, Yuichiro; Fujita, Masaki; Hoshino, Yoshihiko; Betsuyaku, Tomoko; Hasegawa, Naoki

2018-01-02

Presence of Mycobacterium fortuitum in respiratory tracts usually indicates mere colonization or transient infection, whereas true pulmonary infection occurs in patients with gastroesophageal disease. However, little is known about the diagnostic indications for true M. fortuitum pulmonary infection and the natural history of the disease. A 59-year-old man was referred to our hospital for treatment against M. fortuitum pulmonary infection. Fifteen years before the referral, he underwent total gastrectomy, after which he experienced esophageal reflux symptoms. After the referral, the patient was closely monitored without antimicrobial therapy because of mild symptoms and no pathological evidence of M. fortuitum pulmonary infection. During the observation, chest imaging showed migratory infiltrates. Two years after the referral, his lung biopsy specimen revealed foamy macrophages and multinucleated giant cells, indicating lipoid pneumonia. However, he was continually monitored without any treatment because there was no evidence of nontuberculous mycobacterial infection. Four years after the referral, he developed refractory pneumonia despite receiving adequate antibiotic therapy. After confirmation of granulomatous lesions, multiple antimicrobial therapy for M. fortuitum resulted in a remarkable improvement with no exacerbation for over 5 years. Random amplified polymorphic DNA polymerase chain reaction analysis revealed identical M. fortuitum strains in seven isolates from six sputum and one intestinal fluid specimens obtained during the course of the disease. We have described a patient with M. fortuitum pulmonary infection who presented with migratory infiltrates. The pathological evidence and microbiological analysis suggested that M. fortuitum pulmonary infection was associated with lipoid pneumonia and chronic exposure to gastrointestinal fluid. Therefore, physicians should carefully monitor patients with M. fortuitum detected from lower respiratory tract

Prevalence and Risk Factors for Mycobacterium bovis Infection in African Lions ( Panthera leo ) in the Kruger National Park.

PubMed

Sylvester, Tashnica Taime; Martin, Laura Elizabeth Rosen; Buss, Peter; Loxton, Andre Gareth; Hausler, Guy Anton; Rossouw, Leana; van Helden, Paul; Parsons, Sven David Charles; Olea-Popelka, Francisco; Miller, Michele Ann

2017-04-01

Mycobacterium bovis, the causative agent of bovine tuberculosis (BTB), is endemic in the Kruger National Park (KNP), South Africa. African lions ( Panthera leo ) are susceptible to BTB, but the impact of the disease on lion populations is unknown. In this study, we used a novel gene expression assay for chemokine (C-X-C motif) ligand 9 (CXCL9) to measure the prevalence of M. bovis infection in 70 free-ranging lions that were opportunistically sampled in the southern and central regions of the KNP. In the southern region of the KNP, the apparent prevalence of M. bovis infection was 54% (95% confidence interval [CI]=36.9-70.5%), compared with 33% (95% CI=18.0-51.8%) in the central region, an important difference (P=0.08). Prevalence of M. bovis infection in lions showed similar patterns to estimated BTB prevalence in African buffaloes ( Syncerus caffer ) in the same areas. Investigation of other risk factors showed a trend for older lions, males, or lions with concurrent feline immunodeficiency virus infection to have a higher M. bovis prevalence. Our findings demonstrate that the CXCL9 gene expression assay is a useful tool for the determination of M. bovis status in free-ranging lions and identifies important epidemiologic trends for future studies.

Draft Genome Sequence of Mycobacterium triplex DSM 44626.

PubMed

Sassi, Mohamed; Croce, Olivier; Robert, Catherine; Raoult, Didier; Drancourt, Michel

2014-05-29

We announce the draft genome sequence of Mycobacterium triplex strain DSM 44626, a nontuberculosis species responsible for opportunistic infections. The genome described here is composed of 6,382,840 bp, with a G+C content of 66.57%, and contains 5,988 protein-coding genes and 81 RNA genes. Copyright © 2014 Sassi et al.

Hand Infections

MedlinePlus

... drainage or pus should be sent for laboratory testing to determine the type of bacteria causing the infection and the appropriate antibiotic for treatment. CAUSES Atypical Mycobacterial Infections Rarely, a ...

In vitro infection with Mycobacterium tuberculosis induces a distinct immunological pattern in blood from healthy relatives of tuberculosis patients.

PubMed

Juan-García, Javier; García-García, Silvia; Guerra-Laso, José Manuel; Raposo-García, Sara; Diez-Tascón, Cristina; Nebreda-Mayoral, Teresa; López-Fidalgo, Eduardo; López-Medrano, Ramiro; Fernández-Maraña, Araceli; Rivero-Lezcano, Octavio Miguel

2017-11-30

Part of the susceptibility to tuberculosis has a genetic basis, which is clear in primary immunodeficiencies, but is less evident in apparently immunocompetent subjects. Immune responses were analysed in blood samples from tuberculosis patients and their healthy first-degree relatives who were infected in vitro with mycobacteria (either Mycobacterium tuberculosis or M. bovis BCG). The antimicrobial activity against M. tuberculosis in blood from relatives was significantly lower than that observed in healthy controls. Tuberculosis patients exhibited a higher number of neutrophils, and monocyte phagocytosis was inhibited in both relatives and tuberculosis patients. A remarkable finding was that the production of reactive oxygen species by infected neutrophils was higher in relatives than in healthy controls. A higher production of TNFα in infected blood from relatives was also observed. These results may indicate that relatives display a stronger inflammatory response and that their immune response to M. tuberculosis is different from those of unrelated controls. First-degree relatives may represent a highly informative group for the analysis of tuberculosis susceptibility. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Maxillary Teeth Abscesses Result in Atypical Liver Abscesses

PubMed Central

Gupta, Vritti; Vivekanandan, Renuga; Gorby, Gary

2018-01-01

Hepatic liver abscesses are often misdiagnosed on initial presentation because pyogenic liver lesions are a rare occurrence in the United States. This leads to a delay in proper treatment and results in increasing morbidity and mortality. Our case report demonstrates the atypical presentation of a hepatic liver abscess in the elderly. The source of infection was found to be periapical abscesses of the teeth, which subsequently seeded the portal blood stream of our patient. Our findings validate the potential hazard of Viridans streptococci and illustrate how untreated dental infections can serve as a reservoir for a systemic infection. PMID:29796365

The Role of B Cells and Humoral Immunity in Mycobacterium tuberculosis Infection

PubMed Central

Kozakiewicz, Lee; Phuah, Jiayao; Flynn, JoAnne

2014-01-01

Tuberculosis (TB) remains a serious threat to public health, causing 2 million deaths annually world-wide. The control of TB has been hindered by the requirement of long duration of treatment involving multiple chemotherapeutic agents, the increased susceptibility to Mycobacterium tuberculosis infection in the HIV-infected population, and the development of multi-drug resistant and extensively resistant strains of tubercle bacilli. An efficacious and cost-efficient way to control TB is the development of effective anti-TB vaccines. This measure requires thorough understanding of the immune response to M. tuberculosis. While the role of cell-mediated immunity in the development of protective immune response to the tubercle bacillus has been well established, the role of B cells in this process is not clearly understood. Emerging evidence suggests that B cells and humoral immunity can modulate the immune response to various intracellular pathogens, including M. tuberculosis. These lymphocytes form conspicuous aggregates in the lungs of tuberculous humans, non-human primates, and mice, which display features of germinal center B cells. In murine TB, it has been shown that B cells can regulate the level of granulomatous reaction, cytokine production, and the T cell response. This chapter discusses the potential mechanisms by which specific functions of B cells and humoral immunity can shape the immune response to intracellular pathogens in general, and to M. tuberculosis in particular. Knowledge of the B cell-mediated immune response to M. tuberculosis may lead to the design of novel strategies, including the development of effective vaccines, to better control TB. PMID:23468112

Mycobacterium saopaulense sp. nov., a rapidly growing mycobacterium closely related to members of the Mycobacterium chelonae–Mycobacterium abscessus group

PubMed Central

Nogueira, Christiane Lourenço; Whipps, Christopher M.; Matsumoto, Cristianne Kayoko; Chimara, Erica; Droz, Sara; Tortoli, Enrico; de Freitas, Denise; Cnockaert, Margo; Palomino, Juan Carlos; Martin, Anandi; Vandamme, Peter

2015-01-01

Five isolates of non-pigmented, rapidly growing mycobacteria were isolated from three patients and, in an earlier study, from zebrafish. Phenotypic and molecular tests confirmed that these isolates belong to the Mycobacterium chelonae–Mycobacterium abscessus group, but they could not be confidently assigned to any known species of this group. Phenotypic analysis and biochemical tests were not helpful for distinguishing these isolates from other members of the M. chelonae–M. abscessus group. The isolates presented higher drug resistance in comparison with other members of the group, showing susceptibility only to clarithromycin. The five isolates showed a unique PCR restriction analysis pattern of the hsp65 gene, 100 % similarity in 16S rRNA gene and hsp65 sequences and 1–2 nt differences in rpoB and internal transcribed spacer (ITS) sequences. Phylogenetic analysis of a concatenated dataset including 16S rRNA gene, hsp65, and rpoB sequences from type strains of more closely related species placed the five isolates together, as a distinct lineage from previously described species, suggesting a sister relationship to a group consisting of M. chelonae, Mycobacterium salmoniphilum, Mycobacterium franklinii and Mycobacterium immunogenum. DNA–DNA hybridization values >70 % confirmed that the five isolates belong to the same species, while values < 70 % between one of the isolates and the type strains of M. chelonae and M. abscessus confirmed that the isolates belong to a distinct species. The polyphasic characterization of these isolates, supported by DNA–DNA hybridization results, demonstrated that they share characteristics with M. chelonae–M. abscessus members, but constitute a different species, for which the name Mycobacterium saopaulense sp. nov. is proposed. The type strain is EPM 10906T ( = CCUG 66554T = LMG 28586T = INCQS 0733T). PMID:26358475

Nitazoxanide is active against Mycobacterium leprae

PubMed Central

Bailey, Mai Ann; Na, Hana; Duthie, Malcolm S.; Gillis, Thomas P.; Lahiri, Ramanuj

2017-01-01

Nitazoxanide (NTZ) is an anti-parasitic drug that also has activity against bacteria, including Mycobacterium tuberculosis. Our data using both radiorespirometry and live-dead staining in vitro demonstrate that NTZ similarly has bactericidal against M. leprae. Further, gavage of M. leprae-infected mice with NTZ at 25mg/kg provided anti-mycobacterial activity equivalent to rifampicin (RIF) at 10 mg/kg. This suggests that NTZ could be considered for leprosy treatment. PMID:28850614

The seal tuberculosis agent, Mycobacterium pinnipedii, infects domestic cattle in New Zealand: epidemiologic factors and DNA strain typing.

PubMed

Loeffler, Scott H; de Lisle, Geoffrey W; Neill, Mark A; Collins, Desmond M; Price-Carter, Marian; Paterson, Brent; Crews, Kevin B

2014-04-01

The fur seal (Arctocephalus forsteri), which is abundant in coastal areas of New Zealand, harbors several zoonotic pathogens, including Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex. We describe the microbiology and epidemiology of seven cases of M. pinnipedii infection in beef cattle (Bos primigenius) in coastal areas of New Zealand in 1991-2011. Epidemiologic factors were analyzed on six case farms and a telephone survey of 55 neighboring farms. A DNA-strain typing, using analysis of variable number tandem repeats and the direct repeats (VNTR/DR) of those isolates, was used to compare them to M. bovis isolates commonly found in New Zealand cattle and wildlife. In all cases of M. pinnipedii in cattle, only one animal in the herd was found to be infected. In six of seven cases, the lesions were in the thoracic lymph nodes, indicating a likely aerosol pathway. The lack of multiple cases within a herd suggests that cow-to-cow transmission is uncommon, if it occurs at all. There was no significant difference between case and control farms in distance to sea, herd size, herd type, or farming practice. The odds ratio for access to the beach for cattle on the Chatham Islands was significantly higher than it was for farms on the mainland coastal areas (odds ratio [OR] = 3.6, 95% CI = 1.1-11.4) Likewise, the odds ratio for acquiring tuberculosis was increased when farmers had seen seals on the property (OR =  9, 95% CI = 1.4-56.1 ). In all case farms, cattle had access to seals by beach grazing areas or waterways connecting directly with the ocean. The VNTR/DR typing of the isolates showed some variation in the M. pinnipedii isolates, with only two being identical; all isolates were easily distinguishable from M. bovis isolates.

Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae.

PubMed

Medeiros, Rychelle Clayde Affonso; Girardi, Karina do Carmo de Vasconcelos; Cardoso, Fernanda Karlla Luz; Mietto, Bruno de Siqueira; Pinto, Thiago Gomes de Toledo; Gomez, Lilian Sales; Rodrigues, Luciana Silva; Gandini, Mariana; Amaral, Julio Jablonski; Antunes, Sérgio Luiz Gomes; Corte-Real, Suzana; Rosa, Patricia Sammarco; Pessolani, Maria Cristina Vidal; Nery, José Augusto da Costa; Sarno, Euzenir Nunes; Batista-Silva, Leonardo Ribeiro; Sola-Penna, Mauro; Oliveira, Marcus Fernandes; Moraes, Milton Ozório; Lara, Flavio Alves

2016-10-07

Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Association of quantitative interferon-γ responses with the progression of naturally acquired Mycobacterium bovis infection in wild European badgers (Meles meles)

PubMed Central

Tomlinson, Alexandra J; Chambers, Mark A; McDonald, Robbie A; Delahay, Richard J

2015-01-01

Bovine tuberculosis is one of the biggest challenges facing cattle farming in Great Britain. European badgers (Meles meles) are a reservoir host for the causal agent, Mycobacterium bovis. There have been significant recent advances in diagnostic testing for tuberculosis in humans, cattle and badgers, with the development of species-specific assays for interferon-γ (IFN-γ), an important cytokine in tuberculous infections. Using data collected from longitudinal studies of naturally infected wild badgers, we report that the magnitude of the IFN-γ response to M. bovis antigens at the disclosing test event was positively correlated with subsequent progression of disease to a seropositive or excreting state. In addition, we show that the magnitude of the IFN-γ response, despite fluctuation, declined with time after the disclosing event for all badgers, but remained significantly higher in those animals with evidence of disease progression. We discuss how our findings may be related to the immunopathogenesis of natural M. bovis infection in badgers. PMID:25109384

Shared Mycobacterium avium genotypes observed among unlinked clinical and environmental isolates

EPA Science Inventory

Our understanding of the sources of Mycobacterium avium infection is partially based on genotypic matching of pathogen isolates from cases and environmental sources. These approaches assume that genotypic identity is rare in isolates from unlinked cases or sources. To test this, ...

Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

PubMed Central

Kammüller, Michael; Tsai, Tsen-Fang; Griffiths, Christopher EM; Kapoor, Nidhi; Kolattukudy, Pappachan E; Brees, Dominique; Chibout, Salah-Dine; Safi Jr, Jorge; Fox, Todd

2017-01-01

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections. PMID:28868144

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil.

PubMed

Silva, Marcio Roberto; Rocha, Adalgiza da Silva; da Costa, Ronaldo Rodrigues; de Alencar, Andrea Padilha; de Oliveira, Vania Maria; Fonseca Júnior, Antônio Augusto; Sales, Mariana Lázaro; Issa, Marina de Azevedo; Filho, Paulo Martins Soares; Pereira, Omara Tereza Vianello; dos Santos, Eduardo Calazans; Mendes, Rejane Silva; Ferreira, Angela Maria de Jesus; Mota, Pedro Moacyr Pinto Coelho; Suffys, Philip Noel; Guimarães, Mark Drew Crosland

2013-05-01

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.

Photodynamic inactivation of the models Mycobacterium phlei and Mycobacterium smegmatis in vitro

NASA Astrophysics Data System (ADS)

Bruce-Micah, R.; Gamm, U.; Hüttenberger, D.; Cullum, J.; Foth, H.-J.

2009-07-01

Photodynamic inactivation (PDI) of bacterial strains presents an attractive potential alternative to antibiotic therapies. Success is dependent on the effective accumulation in bacterial cells of photochemical substances called photosensitizers, which are usually porphyrins or their derivatives. The kinetics of porphyrin synthesis after treatment with the precursor ALA and the accumulation of the Chlorin e6 and the following illumination were studied. The goal was to estimate effectivity of the destructive power of these PS in vitro in respect of the physiological states of Mycobacteria. So the present results examine the cell destruction by PDI using ALA-induced Porphyrins and Chlorin e6 accumulated in Mycobacterium phlei and Mycobacterium smegmatis, which serve as models for the important pathogens Mycobacterium tuberculosis, Mycobacterium leprae and Mycobacterium bovis. We could show that both Mycobacterium after ALA and Chlorin e6 application were killed by illumination with light of about 662 nm. A reduction of about 97% could be reached by using a lightdose of 70 mW/cm2.

Meta-analysis of human gene expression in response to Mycobacterium tuberculosis infection reveals potential therapeutic targets.

PubMed

Wang, Zhang; Arat, Seda; Magid-Slav, Michal; Brown, James R

2018-01-10

With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection. In contrast, no gene was significant for latent tuberculosis. Pathway enrichment analysis identified 90 significant canonical human pathways, including several pathways more commonly related to non-infectious diseases such as the LRRK2 pathway in Parkinson's disease, and PD-1/PD-L1 signaling pathway important for new immuno-oncology therapies. The analysis of human genome-wide association studies datasets revealed tuberculosis-associated genetic variants proximal to several genes in major histocompatibility complex for antigen presentation. We propose several new targets and drug-repurposing opportunities including intravenous immunoglobulin, ion-channel blockers and cancer immuno-therapeutics for development as combination therapeutics with anti-mycobacterial agents. Our meta-analysis provides novel insights into host genes and pathways important for tuberculosis and brings forth potential drug repurposing opportunities for host-directed therapies.

Whole-genome sequence analysis of the Mycobacterium avium complex and proposal of the transfer of Mycobacterium yongonense to Mycobacterium intracellulare subsp. yongonense subsp. nov.

PubMed

Castejon, Maria; Menéndez, Maria Carmen; Comas, Iñaki; Vicente, Ana; Garcia, Maria J

2018-06-01

Bacterial whole-genome sequences contain informative features of their evolutionary pathways. Comparison of whole-genome sequences have become the method of choice for classification of prokaryotes, thus allowing the identification of bacteria from an evolutionary perspective, and providing data to resolve some current controversies. Currently, controversy exists about the assignment of members of the Mycobacterium avium complex, as is for the cases of Mycobacterium yongonense and 'Mycobacterium indicus pranii'. These two mycobacteria, closely related to Mycobacterium intracellulare on the basis of standard phenotypic and single gene-sequences comparisons, were not considered a member of such species on the basis on some particular differences displayed by a single strain. Whole-genome sequence comparison procedures, namely the average nucleotide identity and the genome distance, showed that those two mycobacteria should be considered members of the species M. intracellulare. The results were confirmed with other whole-genome comparison supplementary methods. According to the data provided, Mycobacterium yongonense and 'Mycobacterium indicus pranii' should be considered and renamed and included as members of M. intracellulare. This study highlights the problems caused when a novel species is accepted on the basis of a single strain, as was the case for M. yongonense. Based mainly on whole-genome sequence analysis, we conclude that M. yongonense should be reclassified as a subspecies of Mycobacterium intracellulareas Mycobacterium intracellularesubsp. yongonense and 'Mycobacterium indicus pranii' classified in the same subspecies as the type strain of Mycobacterium intracellulare and classified as Mycobacterium intracellularesubsp. intracellulare.

Mycobacterium lentiflavum in Drinking Water Supplies, Australia

PubMed Central

Carter, Robyn; Torbey, Matthew J.; Minion, Sharri; Tolson, Carla; Sidjabat, Hanna E.; Huygens, Flavia; Hargreaves, Megan; Thomson, Rachel M.

2011-01-01

Mycobacterium lentiflavum, a slow-growing nontuberculous mycobacterium, is a rare cause of human disease. It has been isolated from environmental samples worldwide. To assess the clinical significance of M. lentiflavum isolates reported to the Queensland Tuberculosis Control Centre, Australia, during 2001–2008, we explored the genotypic similarity and geographic relationship between isolates from humans and potable water in the Brisbane metropolitan area. A total of 47 isolates from 36 patients were reported; 4 patients had clinically significant disease. M. lentiflavum was cultured from 13 of 206 drinking water sites. These sites overlapped geographically with home addresses of the patients who had clinically significant disease. Automated repetitive sequence–based PCR genotyping showed a dominant environmental clone closely related to clinical strains. This finding suggests potable water as a possible source of M. lentiflavum infection in humans. PMID:21392429

The management of infection with Mycobacterium tuberculosis in young children post-2015: an opportunity to close the policy-practice gap.

PubMed

Graham, Stephen M

2017-01-01

The treatment of infection with Mycobacterium tuberculosis in young children is supported by universal policy based on strong rationale and evidence of effectiveness, but has rarely been implemented in tuberculosis endemic countries. Areas covered: This review highlights a number of important recent developments that provide an unprecedented opportunity to close the policy-practice gap, as well as ongoing needs to facilitate implementation under programmatic conditions and scale-up. Expert commentary: The WHO's End TB Strategy and Stop TB Partnership's Plan to End TB provide ambitious targets for prevention at a time when National Tuberculosis Programs in tuberculosis endemic countries are increasing attention to the challenges of management and prevention of tuberculosis disease in children. This opportunity is greatly enhanced by recent evidence of the effectiveness of shorter, simpler and safer regimens to treat tuberculosis infection. The scale of the challenge for implementation will require a decentralized, integrated, community-based approach. An accurate and low-cost point-of-care test for tuberculous infection would be a major advance to support such implementation. Specific guidance for the treatment of infection in young child contacts of multidrug-resistant tuberculosis cases is a major current need while awaiting further evidence.

A Pilot Study Exploring the Use of Breath Analysis to Differentiate Healthy Cattle from Cattle Experimentally Infected with Mycobacterium bovis

PubMed Central

Ellis, Christine K.; Stahl, Randal S.; Nol, Pauline; Waters, W. Ray; Palmer, Mitchell V.; Rhyan, Jack C.; VerCauteren, Kurt C.; McCollum, Matthew; Salman, M. D.

2014-01-01

Bovine tuberculosis, caused by Mycobacterium bovis, is a zoonotic disease of international public health importance. Ante-mortem surveillance is essential for control; however, current surveillance tests are hampered by limitations affecting ease of use or quality of results. There is an emerging interest in human and veterinary medicine in diagnosing disease via identification of volatile organic compounds produced by pathogens and host-pathogen interactions. The objective of this pilot study was to explore application of existing human breath collection and analysis methodologies to cattle as a means to identify M. bovis infection through detection of unique volatile organic compounds or changes in the volatile organic compound profiles present in breath. Breath samples from 23 male Holstein calves (7 non-infected and 16 M. bovis-infected) were collected onto commercially available sorbent cartridges using a mask system at 90 days post-inoculation with M. bovis. Samples were analyzed using gas chromatography-mass spectrometry, and chromatographic data were analyzed using standard analytical chemical and metabolomic analyses, principle components analysis, and a linear discriminant algorithm. The findings provide proof of concept that breath-derived volatile organic compound analysis can be used to differentiate between healthy and M. bovis-infected cattle. PMID:24586655

Dysbiosis of the Fecal Microbiota in Cattle Infected with Mycobacterium avium subsp. paratuberculosis

PubMed Central

Vecchiarelli, Bonnie; Indugu, Nagaraju; Kumar, Sanjay; Gallagher, Susan C.; Fyock, Terry L.; Sweeney, Raymond W.

2016-01-01

Johne's disease (JD) is a chronic, intestinal infection of cattle, caused by Mycobacterium avium subsp. paratuberculosis (MAP). It results in granulomatous inflammation of the intestinal lining, leading to malabsorption, diarrhea, and weight loss. Crohn’s disease (CD), a chronic, inflammatory gastrointestinal disease of humans, has many clinical and pathologic similarities to JD. Dysbiosis of the enteric microbiota has been demonstrated in CD patients. It is speculated that this dysbiosis may contribute to the intestinal inflammation observed in those patients. The purpose of this study was to investigate the diversity patterns of fecal bacterial populations in cattle infected with MAP, compared to those of uninfected control cattle, using phylogenomic analysis. Fecal samples were selected to include samples from 20 MAP-positive cows; 25 MAP-negative herdmates; and 25 MAP-negative cows from a MAP-free herd. The genomic DNA was extracted; PCR amplified sequenced on a 454 Roche platform, and analyzed using QIIME. Approximately 199,077 reads were analyzed from 70 bacterial communities (average of 2,843 reads/sample). The composition of bacterial communities differed between the 3 treatment groups (P < 0.001; Permanova test). Taxonomic assignment of the operational taxonomic units (OTUs) identified 17 bacterial phyla across all samples. Bacteroidetes and Firmicutes constituted more than 95% of the bacterial population in the negative and exposed groups. In the positive group, lineages of Actinobacteria and Proteobacteria increased and those of Bacteroidetes and Firmicutes decreased (P < 0.001). Actinobacteria was highly abundant (30% of the total bacteria) in the positive group compared to exposed and negative groups (0.1–0.2%). Notably, the genus Arthrobacter was found to predominate Actinobacteria in the positive group. This study indicates that MAP-infected cattle have a different composition of their fecal microbiota than MAP-negative cattle. PMID:27494144

Dysbiosis of the Fecal Microbiota in Cattle Infected with Mycobacterium avium subsp. paratuberculosis.

PubMed

Fecteau, Marie-Eve; Pitta, Dipti W; Vecchiarelli, Bonnie; Indugu, Nagaraju; Kumar, Sanjay; Gallagher, Susan C; Fyock, Terry L; Sweeney, Raymond W

2016-01-01

Johne's disease (JD) is a chronic, intestinal infection of cattle, caused by Mycobacterium avium subsp. paratuberculosis (MAP). It results in granulomatous inflammation of the intestinal lining, leading to malabsorption, diarrhea, and weight loss. Crohn's disease (CD), a chronic, inflammatory gastrointestinal disease of humans, has many clinical and pathologic similarities to JD. Dysbiosis of the enteric microbiota has been demonstrated in CD patients. It is speculated that this dysbiosis may contribute to the intestinal inflammation observed in those patients. The purpose of this study was to investigate the diversity patterns of fecal bacterial populations in cattle infected with MAP, compared to those of uninfected control cattle, using phylogenomic analysis. Fecal samples were selected to include samples from 20 MAP-positive cows; 25 MAP-negative herdmates; and 25 MAP-negative cows from a MAP-free herd. The genomic DNA was extracted; PCR amplified sequenced on a 454 Roche platform, and analyzed using QIIME. Approximately 199,077 reads were analyzed from 70 bacterial communities (average of 2,843 reads/sample). The composition of bacterial communities differed between the 3 treatment groups (P < 0.001; Permanova test). Taxonomic assignment of the operational taxonomic units (OTUs) identified 17 bacterial phyla across all samples. Bacteroidetes and Firmicutes constituted more than 95% of the bacterial population in the negative and exposed groups. In the positive group, lineages of Actinobacteria and Proteobacteria increased and those of Bacteroidetes and Firmicutes decreased (P < 0.001). Actinobacteria was highly abundant (30% of the total bacteria) in the positive group compared to exposed and negative groups (0.1-0.2%). Notably, the genus Arthrobacter was found to predominate Actinobacteria in the positive group. This study indicates that MAP-infected cattle have a different composition of their fecal microbiota than MAP-negative cattle.

First report of Mycobacterium canariasense catheter-related bacteremia in the Americas.

PubMed

Paniz-Mondolfi, Alberto; Ladutko, Lynn; Brown-Elliott, Barbara A; Vasireddy, Ravikiran; Vasireddy, Sruthi; Wallace, Richard J; Jakubiec, Wesley; Brecher, Stephen; Campbell, Sheldon

2014-06-01

Mycobacterium canariasense is a recently described late-pigmenting, rapidly growing mycobacterium linked to bacteremia in patients with underlying malignant diseases. We report a case of M. canariasense infection in a patient from Massachusetts with underlying diffuse B cell lymphoma, which was identified both by multilocus sequence typing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). To our knowledge, this is the first description after its original identification in Spain and the first report of this opportunistic pathogen in the Americas. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Atypical Presentation of C. Difficile Infection: Report of a Case with Literature Review

PubMed Central

Towheed, Arooge; Tul Llah, Sibghat; Bin Abdulhak, Aref; Tilson-Mallett, Nancy R; Salkind, Alan

2016-01-01

Clostridium difficile (C. difficile) is a gram-positive, obligate, anaerobic spore-forming bacillus first reported by Hall and O'Toole in 1935. It occurs mostly after antibiotic use and invariably presents with watery diarrhea. We describe an atypical presentation of C. difficile in a 64-year-old Caucasian female who presented to the our emergency department with abdominal pain, nausea, and vomiting for one day. A complete blood count revealed leukocytosis 30 x 109/L and a subsequent computed tomography (CT) scan of the abdomen and the pelvis, showed fluid filled small bowel loops consistent with enteritis. Her presentation was unusual for lack of diarrhea, the hallmark of C. difficile infection. She was admitted and treated with oral vancomycin. The polymerase chain reaction (PCR) value in the stool for C. difficile was positive. The patient responded very well: her abdominal pain resolved and leukocyte count normalized after a few doses of vancomycin (125 mg po qid). The patient's progress was followed in our clinic for the last three months. PMID:27190728

Identification of the Infection Source of an Outbreak of Mycobacterium Chelonae Keratitis After Laser in Situ Keratomileusis.

PubMed

Nascimento, Heloisa; Viana-Niero, Cristina; Nogueira, Christiane Lourenço; Martins Bispo, Paulo José; Pinto, Fernando; de Paula Pereira Uzam, Camila; Matsumoto, Cristianne Kayoko; Oliveira Machado, Antônia Maria; Leão, Sylvia Cardoso; Höfling-Lima, Ana Luisa; de Freitas, Denise

2018-01-01

Nontuberculous mycobacteria keratitis is a rare but challenging complication of laser in situ keratomileusis (LASIK). This study was conducted to determine the source(s) of infection in a cluster of cases of keratitis after LASIK and to describe this outbreak and patients' outcomes. In this retrospective, case series, single-center study, 86 patients were included who underwent LASIK or photorefractive keratectomy between December 2011 and February 2012. Corneal scrapes from the affected eyes, samples of tap and distilled water, water from the reservoir of the distilling equipment, steamer, and autoclave cassette; antiseptic and anesthetic solutions and surgical instrument imprints were cultivated in liquid and on solid media. Gram-negative bacteria and yeasts were identified using automated systems and mycobacteria by polymerase chain reaction-restriction enzyme analysis of the hsp65 gene (PRA-hsp65) and DNA sequencing. Mycobacterial isolates were typed by pulsed-field gel electrophoresis. The cases and outcomes are described. The main outcome measure was identification of the source(s) of the mycobacterial infections. Eight (15 eyes) of 86 patients (172 eyes) who underwent LASIK developed infections postoperatively; no patients who underwent photorefractive keratectomy developed infections. Mycobacterium chelonae was isolated from 4 eyes. The distilled water collected in the surgical facility contained the same M. chelonae strain isolated from the patients' eyes. Different gram-negative bacteria and yeasts were isolated from samples collected at the clinic but not from the patients' eyes. Tap water distilled locally in surgical facilities may be a source of infection after ocular surgery and its use should be avoided.

Pathology of the emerging Mycobacterium tuberculosis complex pathogen, M. mungi in the banded mongoose (Mungos mungo)

USDA-ARS?s Scientific Manuscript database

Wild banded mongooses (Mungos mungo) in northeastern Botswana and Northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex pathogen (MTC), M. mungi. This pathogen is transmitted environmentally between mongoose hosts through exposure to infected scent marks used in olfactory c...

Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice.

PubMed

Guirado, Evelyn; Amat, Isabel; Gil, Olga; Díaz, Jorge; Arcos, Virginia; Caceres, Neus; Ausina, Vicenç; Cardona, Pere-Joan

2006-04-01

We investigated the protective role of immune-sera against reactivation of Mycobacterium tuberculosis infection in SCID mice and found that passive immunization with sera obtained from mice treated with detoxified M. tuberculosis extracts (delivered in liposomes in a composition known as RUTI) exerted significant protection. Our SCID mouse model consisted of aerosol infection by M. tuberculosis, followed by 3 to 8weeks of chemotherapy with isoniazid+rifampicin (INH+RIF) (25 and 10mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH+RIF) for 8weeks and inoculated with RUTI (HS group) or with normal serum (CT group). Significant differences were found between HS and CT groups in the number of bacilli in the lungs (3.68+/-2.02 vs. 5.72+/-1.41log(10) c.f.u.), extent of pulmonary granulomatomous infiltration (10.33+/-0.67 vs. 31.2+/-1.77%), and percentage of animals without pulmonary abscesses (16.7% vs. 45.5%). These data strongly suggest a protective role of specific antibodies against lung dissemination of M. tuberculosis infection.

Outbreak of Mycobacterium haemophilum infections after permanent makeup of the eyebrows.

PubMed

Giulieri, Stefano; Morisod, Benoit; Edney, Timothy; Odman, Micaela; Genné, Daniel; Malinverni, Raffaele; Hammann, Catherine; Musumeci, Enrico; Voide, Cathy; Greub, Gilbert; Masserey, Eric; Bille, Jacques; Cavassini, Matthias; Jaton, Katia

2011-02-15

We report a Mycobacterium haemophilum outbreak after permanent make-up of the eyebrows performed by the same freelance artist. Twelve patients presented an eyebrow lesion and cervical lymphadenitis. All were treated with antibiotics. Surgery was required in 10 cases. M. haemophilum DNA was identified in the make-up ink.

Atypical pneumonia

MedlinePlus

Walking pneumonia; Community-acquired pneumonia - atypical ... Bacteria that cause atypical pneumonia include: Mycoplasma pneumonia is caused by the bacteria Mycoplasma pneumoniae . It often affects people younger than age 40. Pneumonia due ...

Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

PubMed Central

Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L.; Cai, Ying; Coleman, M. Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J.; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B.; Flynn, JoAnne L.

2013-01-01

Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades. PMID:23716617

Assessment of BCG and inactivated Mycobacterium bovis vaccines in an experimental tuberculosis infection model in sheep.

PubMed

Balseiro, Ana; Altuzarra, Raúl; Vidal, Enric; Moll, Xavier; Espada, Yvonne; Sevilla, Iker A; Domingo, Mariano; Garrido, Joseba M; Juste, Ramón A; Prieto, Miguel; Pérez de Val, Bernat

2017-01-01

Animal tuberculosis (TB) is a complex animal health problem that causes disruption to trade and significant economic losses. TB involves a multi-host system where sheep, traditionally considered a rare host of this infection, have been recently included. The aims of this study were to develop an experimental TB infection model in sheep with a Mycobacterium caprae field strain isolated from a tuberculous diseased ewe, and to use this to evaluate the safety and efficacy of two vaccines against TB in sheep, the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine. Eighteen 2 month-old lambs were experimentally challenged with M. caprae by the endotracheal route (1.5 × 103 CFU). They were separated per treatment group into parenterally vaccinated with a live BCG Danish strain vaccine (n = 6), orally vaccinated with a suspension of HIMB (n = 6) and unvaccinated controls (n = 6). Clinical, immunological, pathological and bacteriological parameters of infection were measured. All lambs were successfully infected and developed gross TB lesions in the respiratory system. The BCG vaccine conferred considerable protection against experimental TB in lambs, as measured by a reduction of the gross lesion volumes and bacterial load. However, HIMB vaccinated animals did not show protection. This study proposes a reliable new experimental model for a better understanding of tuberculosis in sheep. BCG vaccination offers an effective prospect for controlling the disease. Moreover alternative doses and/or routes of administration should be considered to evaluate the efficacy of the HIMB vaccine candidate.

Risk Factors for Mycobacterium abscessus subsp. bolletii infection after laparoscopic surgery during an outbreak in Brazil.