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Sample records for staphylococcus aureus skin

  1. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice

    PubMed Central

    van den Berg, Sanne; de Vogel, Corné P.; van Belkum, Alex; Bakker-Woudenberg, Irma A. J. M.

    2015-01-01

    Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P) or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG) levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect. PMID:26060995

  2. Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection

    PubMed Central

    Popov, Lauren; Kovalski, Joanna; Grandi, Guido; Bagnoli, Fabio; Amieva, Manuel R.

    2014-01-01

    Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue. PMID:24567733

  3. Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection.

    PubMed

    Popov, Lauren; Kovalski, Joanna; Grandi, Guido; Bagnoli, Fabio; Amieva, Manuel R

    2014-01-01

    Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue. PMID:24567733

  4. Beta-Hemolysin Promotes Skin Colonization by Staphylococcus aureus

    PubMed Central

    Katayama, Yuki; Sekine, Miwa; Fukuda, Minoru; Hiramatsu, Keiichi

    2013-01-01

    Colonization by Staphylococcus aureus is a characteristic feature of several inflammatory skin diseases and is often followed by epidermal damage and invasive infection. In this study, we investigated the mechanism of skin colonization by a virulent community-acquired methicillin-resistant S. aureus (CA-MRSA) strain, MW2, using a murine ear colonization model. MW2 does not produce a hemolytic toxin, beta-hemolysin (Hlb), due to integration of a prophage, ϕSa3mw, inside the toxin gene (hlb). However, we found that strain MW2 bacteria that had successfully colonized murine ears included derivatives that produced Hlb. Genome sequencing of the Hlb-producing colonies revealed that precise excision of prophage ϕSa3mw occurred, leading to reconstruction of the intact hlb gene in their chromosomes. To address the question of whether Hlb is involved in skin colonization, we constructed MW2-derivative strains with and without the Hlb gene and then subjected them to colonization tests. The colonization efficiency of the Hlb-producing mutant on murine ears was more than 50-fold greater than that of the mutant without hlb. Furthermore, we also showed that Hlb toxin had elevated cytotoxicity for human primary keratinocytes. Our results indicate that S. aureus Hlb plays an important role in skin colonization by damaging keratinocytes, in addition to its well-known hemolytic activity for erythrocytes. PMID:23292775

  5. Skin bacteriology and the role of Staphylococcus aureus in infection.

    PubMed

    Noble, W C

    1998-12-01

    Many of the staphylococci and coryneforms that inhabit normal human skin do not cause skin disease. Amongst the remainder the mechanisms of pathogenicity vary widely. For Proteus, Pseudomonas and Brevibacterium species proteolysis is a major determinant. The precise role of Corynebacterium minutissimum in erythrasma and the propionibacteria in acne is not known. Staphylococcus aureus, however, produces a wide range of non-specific agents, such as haemolysins and leucocidins as well as highly specific toxins such as the epidermolytic toxins involved in bullous impetigo and scalded skin syndrome. Most of the current attention, however, is devoted to the role of the enterotoxins and toxic shock toxin as superantigens, with emphasis on their role in atopic dermatitis. Molecularly similar toxins in the streptococci play a similar role and may also have a role in the aetiology of psoriasis. PMID:9990407

  6. Epicutaneous model of community-acquired Staphylococcus aureus skin infections.

    PubMed

    Prabhakara, Ranjani; Foreman, Oded; De Pascalis, Roberto; Lee, Gloria M; Plaut, Roger D; Kim, Stanley Y; Stibitz, Scott; Elkins, Karen L; Merkel, Tod J

    2013-04-01

    Staphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistant S. aureus SSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated in S. aureus USA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The T(h)1 and T(h)17 cytokines gamma interferon (IFN-γ), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-α), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site. In vivo neutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection. PMID:23381997

  7. Effect of Substance P in Staphylococcus aureus and Staphylococcus epidermidis Virulence: Implication for Skin Homeostasis

    PubMed Central

    N'Diaye, Awa; Mijouin, Lily; Hillion, Mélanie; Diaz, Suraya; Konto-Ghiorghi, Yoan; Percoco, Giuseppe; Chevalier, Sylvie; Lefeuvre, Luc; Harmer, Nicholas J.; Lesouhaitier, Olivier; Feuilloley, Marc G. J.

    2016-01-01

    Staphylococcus aureus and Staphylococcus epidermidis are two major skin associated bacteria, and Substance P (SP) is a major skin neuropeptide. Since bacteria are known to sense and response to many human hormones, we investigated the effects of SP on Staphylococci virulence in reconstructed human epidermis model and HaCaT keratinocytes. We show that SP is stimulating the virulence of S. aureus and S. epidermidis in a reconstructed human epidermis model. qRT-PCR array analysis of 64 genes expressed by keratinocytes in the response to bacterial infection revealed a potential link between the action of SP on Staphylococci and skin physiopathology. qRT-PCR and direct assay of cathelicidin and human β-defensin 2 secretion also provided that demonstration that the action of SP on bacteria is independent of antimicrobial peptide expression by keratinocytes. Considering an effect of SP on S. aureus and S. epidermidis, we observed that SP increases the adhesion potential of both bacteria on keratinocytes. However, SP modulates the virulence of S. aureus and S. epidermidis through different mechanisms. The response of S. aureus is associated with an increase in Staphylococcal Enterotoxin C2 (SEC2) production and a reduction of exolipase processing whereas in S. epidermidis the effect of SP appears mediated by a rise in biofilm formation activity. The Thermo unstable ribosomal Elongation factor Ef-Tu was identified as the SP-interacting protein in S. aureus and S. epidermidis. SP appears as an inter-kingdom communication factor involved in the regulation of bacterial virulence and essential for skin microflora homeostasis. PMID:27148195

  8. Effect of Substance P in Staphylococcus aureus and Staphylococcus epidermidis Virulence: Implication for Skin Homeostasis.

    PubMed

    N'Diaye, Awa; Mijouin, Lily; Hillion, Mélanie; Diaz, Suraya; Konto-Ghiorghi, Yoan; Percoco, Giuseppe; Chevalier, Sylvie; Lefeuvre, Luc; Harmer, Nicholas J; Lesouhaitier, Olivier; Feuilloley, Marc G J

    2016-01-01

    Staphylococcus aureus and Staphylococcus epidermidis are two major skin associated bacteria, and Substance P (SP) is a major skin neuropeptide. Since bacteria are known to sense and response to many human hormones, we investigated the effects of SP on Staphylococci virulence in reconstructed human epidermis model and HaCaT keratinocytes. We show that SP is stimulating the virulence of S. aureus and S. epidermidis in a reconstructed human epidermis model. qRT-PCR array analysis of 64 genes expressed by keratinocytes in the response to bacterial infection revealed a potential link between the action of SP on Staphylococci and skin physiopathology. qRT-PCR and direct assay of cathelicidin and human β-defensin 2 secretion also provided that demonstration that the action of SP on bacteria is independent of antimicrobial peptide expression by keratinocytes. Considering an effect of SP on S. aureus and S. epidermidis, we observed that SP increases the adhesion potential of both bacteria on keratinocytes. However, SP modulates the virulence of S. aureus and S. epidermidis through different mechanisms. The response of S. aureus is associated with an increase in Staphylococcal Enterotoxin C2 (SEC2) production and a reduction of exolipase processing whereas in S. epidermidis the effect of SP appears mediated by a rise in biofilm formation activity. The Thermo unstable ribosomal Elongation factor Ef-Tu was identified as the SP-interacting protein in S. aureus and S. epidermidis. SP appears as an inter-kingdom communication factor involved in the regulation of bacterial virulence and essential for skin microflora homeostasis. PMID:27148195

  9. Staphylococcus aureus Colonization in Children with Community-Associated Staphylococcus aureus Skin Infections and Their Household Contacts

    PubMed Central

    Fritz, Stephanie A.; Hogan, Patrick G.; Hayek, Genevieve; Eisenstein, Kimberly A.; Rodriguez, Marcela; Krauss, Melissa; Garbutt, Jane; Fraser, Victoria J.

    2013-01-01

    Objectives To measure prevalence of Staphylococcus aureus colonization in household contacts of children with acute S. aureus skin and soft tissue infections (SSTI), determine risk factors for S. aureus colonization in household contacts, and assess anatomic sites of S. aureus colonization in patients and household contacts. Design Cross-sectional study. Setting St. Louis Children’s Hospital Emergency Department and ambulatory wound center and nine community pediatric practices affiliated with a practice-based research network. Participants Patients with community-associated S. aureus SSTI and S. aureus colonization (in the nose, axilla, and/or inguinal folds) and their household contacts. Outcome Measures Colonization of household contacts of pediatric patients with S. aureus colonization and SSTI. Results Of 183 index patients, 61% were colonized with methicillin-resistant S. aureus (MRSA), 30% with methicillin-sensitive S. aureus (MSSA), and 9% with both MRSA and MSSA. Of 609 household contacts, 323 (53%) were colonized with S. aureus: 115 (19%) with MRSA, 195 (32%) with MSSA, and 13 (2%) with both. Parents were more likely than other household contacts to be colonized with MRSA (OR 1.72, 95% CI 1.12, 2.63). MRSA colonized the inguinal folds more frequently than MSSA (OR 1.67, 95% CI 1.16, 2.41), and MSSA colonized the nose more frequently than MRSA (OR 1.75, 95% CI 1.19, 2.56). Conclusions Household contacts of children with S. aureus SSTI had a high rate of MRSA colonization compared to the general population. The inguinal fold is a prominent site of MRSA colonization, which may be an important consideration for active surveillance programs in hospitals. PMID:22665030

  10. Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation.

    PubMed

    Wanke, Ines; Skabytska, Yuliya; Kraft, Beatrice; Peschel, Andreas; Biedermann, Tilo; Schittek, Birgit

    2013-02-01

    Experimental mouse models of bacterial skin infections that have been described show that pathogenic microorganisms can readily invade the epidermis and dermis to produce localized infections. We used an epicutaneous mouse skin infection model to determine how the level of barrier disruption by tape-stripping correlates with persistence of Staphylococcus aureus skin colonization, concomitant induction of cutaneous inflammation and infection. Furthermore, we investigated how murine skin responds to S. aureus colonization in a physiologic setting by analysing proinflammatory cytokines and antimicrobial peptides in mouse skin. We show that previous cutaneous damage allows skin inflammation to develop and favours S. aureus persistence leading to cutaneous colonization, suggesting an interdependence of cutaneous bacteria and skin. Our study suggests that skin barrier defects favour S. aureus skin colonization, which is associated with profound cutaneous inflammation. PMID:23362876

  11. Pharmacokinetics and Pharmacodynamics of Levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in Human Skin Blister Fluid

    PubMed Central

    Trampuz, Andrej; Wenk, Markus; Rajacic, Zarko; Zimmerli, Werner

    2000-01-01

    The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied. SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation. PMID:10770776

  12. Risk Factors for Community-Associated Staphylococcus aureus Skin Infection in Children of Maui

    PubMed Central

    Seifried, Steven E

    2012-01-01

    The prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection, and Staphylococcus aureus (S. aureus) infection overall, has dramatically increased in the past 10 years. Children and Native Hawaiians and Pacific Islanders (NHPI) are disproportionately affected by CA-MRSA infection. The purpose of this case-control study was to identify risk factors for CA-S. aureus skin infections in children of Maui, Hawai‘i, as a foundation for reducing the transmission of these infections. Survey data were obtained from patients in pediatric clinician offices over an 8-month period. NHPI participants were well-represented as 58% of cases and 54% of controls. Chi-square analysis and logistic regression were used to identify risk factors. Significant risk factors predictive of infection among all participants were (a) skin abrasions or wounds, (b) household contact, and (c) overweight or obesity. Risk factors predictive of infection among NHPI were (a) skin abrasions or wounds, (b) antibiotic use within 6 months, (c) overweight or obesity, and (d) a history of eczema or other skin disorder. The role of overweight or obesity in S. aureus skin infections among NHPI has not been identified in previous research and indicates a focus for additional education. Further research is needed to better understand the role of eczema, antibiotic use, overweight and obesity, and socio-cultural factors in these infections. PMID:22900237

  13. Effects of postmilking teat treatment on the colonization of Staphylococcus aureus on chapped teat skin.

    PubMed

    Fox, L K; Nagy, J A; Hillers, J K; Cronrath, J D; Ratkowsky, D A

    1991-06-01

    Sixteen Holstein cows were used to test the effect of postmilking teat treatment on colonization and intramammary infection by Staphylococcus aureus on chapped teats. Treatments were (1) chapping the teat and using 1% I2/10% glycerin postdip solution, (2) 1% I2/10% glycerin postdip solution on nonchapped teats, (3) chapping the teat and using 10% glycerin postdip solution, (4) chapping the teat and not using a postdip solution. All mammary glands were free of S aureus teat skin colonization and intramammary infection at the start of the study. Teats selected for chapping were dipped in 1N NaOH prior to 3 applications of S aureus broth culture; cultures were applied at 12-hour intervals on all teats. Treatments were applied after each milking for 30 days and were initiated after the second broth dip. Teat skin swab specimens and milk samples were collected before treatment application. Teat skin condition was scored daily. Nonchapped teats (treatment 2) did not support skin or orifice colonization by S aureus. Treatment-1 teats healed most rapidly and supported less colonization in skin and orifice than did treatment-3 and -4 teats. Teat skin scores and skin colonization were lower for treatment-3 than treatment-4 teats. A correlation between teat skin colonization and teat skin conditions was found. Two intramammary infections were found in treatment-4 quarters and 1 in a treatment-3 quarter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1883082

  14. The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens

    PubMed Central

    Lacey, Keenan A.; Geoghegan, Joan A.; McLoughlin, Rachel M.

    2016-01-01

    Staphylococcus aureus (S. aureus) causes the vast majority of skin and soft tissue infections (SSTIs) in humans. S. aureus has become increasingly resistant to antibiotics and there is an urgent need for new strategies to tackle S. aureus infections. Vaccines offer a potential solution to this epidemic of antimicrobial resistance. However, the development of next generation efficacious anti-S. aureus vaccines necessitates a greater understanding of the protective immune response against S. aureus infection. In particular, it will be important to ascertain if distinct immune mechanisms are required to confer protection at distinct anatomical sites. Recent discoveries have highlighted that interleukin-17-producing T cells play a particularly important role in the immune response to S. aureus skin infection and suggest that vaccine strategies to specifically target these types of T cells may be beneficial in the treatment of S. aureus SSTIs. S. aureus expresses a large number of cell wall-anchored (CWA) proteins, which are covalently attached to the cell wall peptidoglycan. The virulence potential of many CWA proteins has been demonstrated in infection models; however, there is a paucity of information regarding their roles during SSTIs. In this review, we highlight potential candidate antigens for vaccines targeted at protection against SSTIs. PMID:26901227

  15. Community-associated methicillin-resistant Staphylococcus aureus in non-outbreak skin infections

    PubMed Central

    Bonesso, Mariana Fávero; Marques, Silvio Alencar; Camargo, Carlos Henrique; Fortaleza, Carlos Magno Castelo Branco; da Cunha, Maria de Lourdes Ribeiro de Souza

    2014-01-01

    The aim of this study was to determine the prevalence of Staphylococcus aureus and risk factors for the acquisition of MRSA (Methicillin Resistant Staphylococcus aureus) as the main cause of skin and soft tissue infections. S. aureus were characterized for the presence of PVL, TSST-1 and mecA genes. SCCmec typing was carried out in mecA positive strains and PFGE was performed only in these strains. During the study period, 127 outpatients attending a dermatology clinical the Botucatu Medical School, a regional tertiary hospital in Botucatu, Sao Paulo, Brazil, were diagnosed with active skin infections. A total 66 (56.9%) S. aureus strains were isolated. The methicillin resistance gene mecA was detected in seven (10.6%) S. aureus strains. The SCCmec types detected in the seven mecA-positive S. aureus strains were type Ia in one, type II in three, and type IV in three. The PVL gene was detected in 10 (15.1%) in sensitive strains. Pulsed field gel electrophoresis revealed non-clonal diversity among the isolates. The risk factors associated with MRSA acquisition in this study were previous ciprofloxacin use and working in a healthcare environment. The risk factors indicate plausible routes of CA-MRSA transmission among the subjects studied. PMID:25763047

  16. Community-associated methicillin-resistant Staphylococcus aureus in non-outbreak skin infections.

    PubMed

    Bonesso, Mariana Fávero; Marques, Silvio Alencar; Camargo, Carlos Henrique; Fortaleza, Carlos Magno Castelo Branco; da Cunha, Maria de Lourdes Ribeiro de Souza

    2014-01-01

    The aim of this study was to determine the prevalence of Staphylococcus aureus and risk factors for the acquisition of MRSA (Methicillin Resistant Staphylococcus aureus) as the main cause of skin and soft tissue infections. S. aureus were characterized for the presence of PVL, TSST-1 and mecA genes. SCCmec typing was carried out in mecA positive strains and PFGE was performed only in these strains. During the study period, 127 outpatients attending a dermatology clinical the Botucatu Medical School, a regional tertiary hospital in Botucatu, Sao Paulo, Brazil, were diagnosed with active skin infections. A total 66 (56.9%) S. aureus strains were isolated. The methicillin resistance gene mecA was detected in seven (10.6%) S. aureus strains. The SCCmec types detected in the seven mecA-positive S. aureus strains were type Ia in one, type II in three, and type IV in three. The PVL gene was detected in 10 (15.1%) in sensitive strains. Pulsed field gel electrophoresis revealed non-clonal diversity among the isolates. The risk factors associated with MRSA acquisition in this study were previous ciprofloxacin use and working in a healthcare environment. The risk factors indicate plausible routes of CA-MRSA transmission among the subjects studied. PMID:25763047

  17. Biofilm formation by Staphylococcus aureus isolates from skin and soft tissue infections.

    PubMed

    Kwiecinski, Jakub; Kahlmeter, Gunnar; Jin, Tao

    2015-05-01

    Many diseases caused by Staphylococcus aureus are associated with biofilm formation. However, the ability of S. aureus isolates from skin and soft tissue infections to form biofilms has not yet been investigated. We tested 160 isolates from patients with various skin infections for biofilm-forming capacity in different growth media. All the isolates formed biofilms, the extent of which depended on the type of growth medium. The thickest biofilms were formed when both plasma and glucose were present in the broth; in this case, S. aureus incorporated host fibrin into the biofilm's matrix. There were no differences in the biofilm formation between isolates from different types of skin infections, except for a particularly good biofilm formation by isolates from diabetic wounds and a weaker biofilm formation by isolates from impetigo. In conclusion, biofilm formation is a universal behavior of S. aureus isolates from skin infections. In some cases, such as in diabetic wounds, a particularly strong biofilm formation most likely contributes to the chronic and recurrent character of the infection. Additionally, as S. aureus apparently uses host fibrin as part of the biofilm structure, we suggest that plasma should be included more frequently in in vitro biofilm studies. PMID:25586078

  18. Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection

    PubMed Central

    Tseng, Ching Wen; Kolar, Stacey L.; Müller, Sabrina; Rodriguez, Maria D.; Rezai-Zadeh, Kavon; Fan, Xuemo; Beenhouwer, David O.; Town, Terrence; Liu, George Y.

    2015-01-01

    Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL) elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA), exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD)/severe combined immune deficiency (SCID)/IL2rγnull (NSG) mice engrafted with human CD34+ umbilical cord blood cells. These “humanized” NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor. PMID:26618545

  19. A β-lactone-based antivirulence drug ameliorates Staphylococcus aureus skin infections in mice.

    PubMed

    Weinandy, Franziska; Lorenz-Baath, Katrin; Korotkov, Vadim S; Böttcher, Thomas; Sethi, Shneh; Chakraborty, Trinad; Sieber, Stephan A

    2014-04-01

    Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi-resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life-threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β-lactone-based molecule demonstrated that antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β-lactone significantly decreased abscess size even when applied 6 h post-infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies. PMID:24678014

  20. Methamphetamine Alters the Antimicrobial Efficacy of Phagocytic Cells during Methicillin-Resistant Staphylococcus aureus Skin Infection

    PubMed Central

    Mihu, Mircea Radu; Roman-Sosa, Jessica; Varshney, Avanish K.; Eugenin, Eliseo A.; Shah, Bhavikkumar P.; Ham Lee, Hiu; Nguyen, Long N.; Guimaraes, Allan J.; Fries, Bettina C.; Nosanchuk, Joshua D.

    2015-01-01

    ABSTRACT Methamphetamine (METH) is a major drug of abuse in the United States and worldwide. Furthermore, Staphylococcus aureus infections and METH use are coemerging public health problems. S. aureus is the single most important bacterial pathogen in infections among injection drug users, with skin and soft tissue infections (SSTI) being extremely common. Notably, the incidence of SSTI, especially in drug users, is difficult to estimate because such infections are often self-treated. Although there is substantial information on the behavioral and cognitive defects caused by METH in drug users, there is a dearth of knowledge regarding its impact on bacterial infections and immunity. Therefore, we hypothesized that METH exacerbates S. aureus skin infection. Using a murine model of METH administration and wound infection, we demonstrated that METH reduces wound healing and facilitates host-mediated collagen degradation by increased expression and production of matrix metalloproteinase-2 (MMP-2). Additionally, we found that METH induces S. aureus biofilm formation and leads to detrimental effects on the functions of human and murine phagocytic cells, enhancing susceptibility to S. aureus infection. Our findings provide empirical evidence of the adverse impact of METH use on the antimicrobial efficacy of the cells that comprise innate immunity, the initial host response to combat microbial infection. PMID:26507236

  1. Nursery outbreak of scalded-skin syndrome. Scarlatiniform rash due to phage group I Staphylococcus aureus.

    PubMed

    Faden, H S; Burke, J P; Glasgow, L A; Everett, J R

    1976-03-01

    From Aug 6 to 14, 1973, scariatiniform eruptions that were considered to be mild forms of the staphylococcal scalded-skin syndrome developed in four neonates. One infant had mild epidermal peeling. All had generalized, finely papular erythema that cleared rapidly after treatment with antibiotics. Cultures from the umbilical stumps or anterior nares of three of the infants yielded colonies of group I Staphylococcus aureus, phage type 29/52/79/86/D11/81, that were able to produce epidermal exfoliation in suckling mice. These data indicate that the nursery outbreak was caused by phage group I staphylococci rather than group II organisms previously associated with staphylococcal scalded-skin syndrome. The demonstration that a group I Staphylococcus can produce exfoliative toxin suggests that the same mechanism for toxin production may exist for phage groups I and II staphylococci. PMID:130798

  2. Bactericidal Activity of the Human Skin Fatty Acid cis-6-Hexadecanoic Acid on Staphylococcus aureus

    PubMed Central

    Cartron, Michaël L.; England, Simon R.; Chiriac, Alina Iulia; Josten, Michaele; Turner, Robert; Rauter, Yvonne; Hurd, Alexander; Sahl, Hans-Georg; Jones, Simon

    2014-01-01

    Human skin fatty acids are a potent aspect of our innate defenses, giving surface protection against potentially invasive organisms. They provide an important parameter in determining the ecology of the skin microflora, and alterations can lead to increased colonization by pathogens such as Staphylococcus aureus. Harnessing skin fatty acids may also give a new avenue of exploration in the generation of control measures against drug-resistant organisms. Despite their importance, the mechanism(s) whereby skin fatty acids kill bacteria has remained largely elusive. Here, we describe an analysis of the bactericidal effects of the major human skin fatty acid cis-6-hexadecenoic acid (C6H) on the human commensal and pathogen S. aureus. Several C6H concentration-dependent mechanisms were found. At high concentrations, C6H swiftly kills cells associated with a general loss of membrane integrity. However, C6H still kills at lower concentrations, acting through disruption of the proton motive force, an increase in membrane fluidity, and its effects on electron transfer. The design of analogues with altered bactericidal effects has begun to determine the structural constraints on activity and paves the way for the rational design of new antistaphylococcal agents. PMID:24709265

  3. The receptor for advanced glycation end products promotes bacterial growth at distant body sites in Staphylococcus aureus skin infection.

    PubMed

    Achouiti, Ahmed; Van't Veer, Cornelis; de Vos, Alex F; van der Poll, Tom

    2015-09-01

    The receptor for advanced glycation endproducts (RAGE) has been implicated in the regulation of skin inflammation. We here sought to study the role of RAGE in host defense during skin infection caused by Staphylococcus (S.) aureus, the most common pathogen in this condition. Wild-type (Wt) and RAGE deficient (rage(-/-)) mice were infected subcutaneously with S. aureus and bacterial loads and local inflammation were quantified at regular intervals up to 8 days after infection. While bacterial burdens were similar in both mouse strains at the primary site of infection, rage(-/-) mice had lower bacterial counts in lungs and liver. Skin cytokine and chemokine levels did not differ between groups. In accordance with the skin model, direct intravenous infection with S. aureus was associated with lower bacterial loads in lungs and liver of rage(-/-) mice. Together these data suggest that RAGE does not impact local host defense during S. aureus skin infection, but facilitates bacterial growth at distant body sites. PMID:26086798

  4. Staphylococcus aureus Hijacks a Skin Commensal to Intensify Its Virulence: Immunization Targeting β-Hemolysin and CAMP Factor

    PubMed Central

    Lo, Chih-Wei; Lai, Yiu-Kay; Liu, Yu-Tsueng; Gallo, Richard L.; Huang, Chun-Ming

    2011-01-01

    The need for a new anti-Staphylococcus aureus therapy that can effectively cripple bacterial infection, neutralize secretory virulence factors, and lower the risk of creating bacterial resistance is undisputed. Here, we propose what is, to our knowledge, a previously unreported infectious mechanism by which S. aureus may commandeer Propionibacterium acnes, a key member of the human skin microbiome, to spread its invasion and highlight two secretory virulence factors (S. aureus β-hemolysin and P. acnes CAMP (Christie, Atkins, Munch-Peterson) factor) as potential molecular targets for immunotherapy against S. aureus infection. Our data demonstrate that the hemolysis and cytolysis by S. aureus were noticeably augmented when S. aureus was grown with P. acnes. The augmentation was significantly abrogated when the P. acnes CAMP factor was neutralized or β-hemolysin of S. aureus was mutated. In addition, the hemolysis and cytolysis of recombinant β-hemolysin were markedly enhanced by recombinant CAMP factor. Furthermore, P. acnes exacerbated S. aureus-induced skin lesions in vivo. The combination of CAMP factor neutralization and β-hemolysin immunization cooperatively suppressed the skin lesions caused by coinfection of P. acnes and S. aureus. These observations suggest a previously unreported immunotherapy targeting the interaction of S. aureus with a skin commensal. PMID:21085191

  5. Reduction in Staphylococcus aureus bacteraemia rates in patients receiving haemodialysis following alteration of skin antisepsis procedures.

    PubMed

    Stewart, B J; Gardiner, T; Perry, G J; Tong, S Y C

    2016-02-01

    This study examined all cases of Staphylococcus aureus bacteraemia (SAB) in the haemodialysis cohort at the Royal Darwin Hospital, Australia over a seven-year period. Midway through this period, antisepsis for arteriovenous fistulae (AVF) and central venous catheters (CVC) changed from 0.5% chlorhexidine solution to 2% chlorhexidine solution. Rates of SAB episodes were calculated using registry data. Trends in SAB over time were analysed using an interrupted regression analysis. Following the change to 2% chlorhexidine, average SAB rates decreased by 68%, and it is estimated that 0.111 cases of SAB/patient-year were prevented. CVC-related SAB rates remained low throughout. These results support the use of 2% chlorhexidine in skin antisepsis for patients with AVF. PMID:26778135

  6. Efficacy of Lantibiotic Treatment of Staphylococcus aureus-Induced Skin Infections, Monitored by In Vivo Bioluminescent Imaging.

    PubMed

    van Staden, Anton Du Preez; Heunis, Tiaan; Smith, Carine; Deane, Shelly; Dicks, Leon M T

    2016-07-01

    Staphylococcus aureus is a bacterial pathogen responsible for the majority of skin and soft tissue infections. Antibiotics are losing their efficacy as treatment for skin and soft tissue infections as a result of increased resistance in a variety of pathogens, including S. aureus It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options for skin and soft tissue infections. A select few lantibiotics, a group of natural defense peptides produced by bacteria, inhibit the growth of numerous clinical S. aureus isolates, including methicillin-resistant strains. In this study, the antimicrobial activities of nisin, clausin, and amyloliquecidin, separately administered, were compared to that of a mupirocin-based ointment, which is commonly used as treatment for S. aureus-induced skin infections. Full-thickness excisional wounds, generated on the dorsal surfaces of mice, were infected with a bioluminescent strain of S. aureus (strain Xen 36). The infections were monitored in real time using in vivo bioluminescent imaging. Lantibiotic treatments significantly reduced the bioluminescence of S. aureus Xen 36 to a level similar to that recorded with mupirocin treatment. Wound closure, however, was more pronounced during lantibiotic treatment. Lantibiotics thus have the potential to be used as an alternative treatment option for S. aureus-induced skin infections. PMID:27067340

  7. Skin-Specific Unsaturated Fatty Acids Boost the Staphylococcus aureus Innate Immune Response

    PubMed Central

    Nguyen, Minh Thu; Hanzelmann, Dennis; Härtner, Thomas; Peschel, Andreas

    2015-01-01

    Antimicrobial fatty acids (AFAs) protect the human epidermis against invasion by pathogenic bacteria. In this study, we questioned whether human skin fatty acids (FAs) can be incorporated into the lipid moiety of lipoproteins and whether such incorporation would have an impact on innate immune stimulation in the model organism Staphylococcus aureus USA300 JE2. This organism synthesized only saturated FAs. However, when feeding USA300 with unsaturated FAs present on human skin (C16:1, C18:1, or C18:2), those were taken up, elongated stepwise by two carbon units, and finally found in the bacterial (phospho)lipid fraction. They were also observed in the lipid moiety of lipoproteins. When USA300 JE2 was fed with the unsaturated FAs, the cells and cell lysates showed an increased innate immune activation with various immune cells and peripheral blood mononuclear cells (PBMCs). Immune activation was highest with linoleic acid (C18:2). There are several pieces of evidence that the enhanced immune stimulating effect was due to the incorporation of unsaturated FAs in lipoproteins. First, the enhanced stimulation was dependent on Toll-like receptor 2 (TLR2). Second, an lgt mutant, unable to carry out lipidation of prolipoproteins, was unable to carry out immune stimulation when fed with unsaturated FAs. Third, the supplied FAs did not significantly affect growth, protein release, or expression of the model lipoprotein Lpl1. Although S. aureus is unable to synthesize unsaturated FAs, it incorporates long-chain unsaturated FAs into its lipoproteins, with the effect that the cells are better recognized by the innate immune system. This is an additional mechanism how our skin controls bacterial colonization and infection. PMID:26502910

  8. Skin-Specific Unsaturated Fatty Acids Boost the Staphylococcus aureus Innate Immune Response.

    PubMed

    Nguyen, Minh Thu; Hanzelmann, Dennis; Härtner, Thomas; Peschel, Andreas; Götz, Friedrich

    2016-01-01

    Antimicrobial fatty acids (AFAs) protect the human epidermis against invasion by pathogenic bacteria. In this study, we questioned whether human skin fatty acids (FAs) can be incorporated into the lipid moiety of lipoproteins and whether such incorporation would have an impact on innate immune stimulation in the model organism Staphylococcus aureus USA300 JE2. This organism synthesized only saturated FAs. However, when feeding USA300 with unsaturated FAs present on human skin (C16:1, C18:1, or C18:2), those were taken up, elongated stepwise by two carbon units, and finally found in the bacterial (phospho)lipid fraction. They were also observed in the lipid moiety of lipoproteins. When USA300 JE2 was fed with the unsaturated FAs, the cells and cell lysates showed an increased innate immune activation with various immune cells and peripheral blood mononuclear cells (PBMCs). Immune activation was highest with linoleic acid (C18:2). There are several pieces of evidence that the enhanced immune stimulating effect was due to the incorporation of unsaturated FAs in lipoproteins. First, the enhanced stimulation was dependent on Toll-like receptor 2 (TLR2). Second, an lgt mutant, unable to carry out lipidation of prolipoproteins, was unable to carry out immune stimulation when fed with unsaturated FAs. Third, the supplied FAs did not significantly affect growth, protein release, or expression of the model lipoprotein Lpl1. Although S. aureus is unable to synthesize unsaturated FAs, it incorporates long-chain unsaturated FAs into its lipoproteins, with the effect that the cells are better recognized by the innate immune system. This is an additional mechanism how our skin controls bacterial colonization and infection. PMID:26502910

  9. The efficacy of ethanolic extract of Lemon verbena on the skin infection due to Staphylococcus aureus in an animal model.

    PubMed

    Ghaemi, Ezzat Ollah; Khorshidi, Didar; Moradi, Abdolvahab; Seifi, Akhter; Mazendrani, Masomeh; Bazouri, Masod; Mansourian, Azad Reza

    2007-11-15

    Daily increasing of Staphylococcus aureus resistance to various antibiotics in particular penicillin and Methecilin has led the scientist to look fore new medicines in this area. In an in vitro laboratory studies, it has been demonstrated that ethanolic extract of Lemon verbena can prevent the growth of Staphylococcus aureus. In this study the efficacy of ethanolic extract of Lemon verbena against Staphylococcus aureus skin infection were assessed in an in vivo, in animal model. 200lambda of Staphylococcus aureus suspension, were inoculated intradermally on the shoulder of 63 laboratory 20-30 g mice. the mice were divided in to 4 groups, 2 control groups: Negative (without treatment) and positive (treated with Mupirucin) and 2 test groups that treated for 7 days by ointment prepared from ethanolic extract of Lemon verbena (group 3), or injection of Lemon verbena solution (group 4). The status of wounds, the rate of recovery was studied and the presence of local pus after dissection of mice on day 8 recorded and compared with each other. The wound appearance in the second day, on the injection site of S. aureus, in Group 1, 4, 3 and 2 were 84.2, 66.7, 46.2 and 23.1%, respectively. In the final day, the lesion still was remained in 78.9, 23.1, 92.3 and 77.7% in groups 1 -4, respectively. The necrotic and wide wounds were more observed in groups 1 and 3 vs two other groups. The results from this investigation indicate that the ointment prepared from ethanolic extract of Lemon verbena is a proper medication to prevent the skin infection by Staphylococcus aureus in early phase. PMID:19090293

  10. Molecular characterization of Staphylococcus aureus isolates causing skin and soft tissue infections in patients from Malakand, Pakistan.

    PubMed

    Madzgalla, S; Syed, M A; Khan, M A; Rehman, S S; Müller, E; Reissig, A; Ehricht, R; Monecke, S

    2016-09-01

    Comparatively few studies have been published describing Staphylococcus aureus/MRSA epidemiology in Central Asia including Pakistan. Here, we report the genotyping of Staphylococcus aureus strains (that include both methicillin-susceptible and methicillin-resistant Staphylococcus aureus) from community- and hospital-acquired skin and soft-tissue infections in a tertiary care hospital in the Malakand district of the Khyber Pakhtunkhwa Province of Pakistan. Forty-five isolates of Staphylococcus aureus were characterized by microarray hybridization. Twenty isolates (44 %) were MRSA, whereas 22 (49 %) were PVL-positive. Fourteen isolates (31 %) harboured both mecA and PVL genes. The dominant clones were CC121-MSSA (n = 15, 33 %) and the PVL-positive "Bengal Bay Clone" (ST772-MRSA-V; n = 13, 29 %). The PVL-positive CC8-MRSA-IV strain "USA300" was found once. The pandemic ST239-MRSA-III strain was absent, although it has previously been observed in Pakistan. These observations require a re-assessment of schemes for initial antibiotic therapy to cover MRSA and they emphasise the need for a rapid and non-molecular test for PVL. PMID:27262852

  11. A Novel Chimeric Lysin Shows Superiority to Mupirocin for Skin Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains▿

    PubMed Central

    Pastagia, Mina; Euler, Chad; Chahales, Peter; Fuentes-Duculan, Judilyn; Krueger, James G.; Fischetti, Vincent A.

    2011-01-01

    Staphylococcus aureus is a major human pathogen responsible for a number of serious and sometimes fatal infections. One of its reservoirs on the human body is the skin, which is known to be a source of invasive infection. The potential for an engineered staphylococcus-specific phage lysin (ClyS) to be used for topical decolonization is presented. We formulated ClyS into an ointment and applied it to a mouse model of skin colonization/infection with S. aureus. Unlike the standard topical antibacterial agent mupirocin, ClyS eradicated a significantly greater number of methicillin-susceptible S. aureus (MSSA) and -resistant S. aureus (MRSA) bacteria: a 3-log reduction with ClyS as opposed to a 2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a decreased potential for the development of resistance by MRSA and MSSA organisms compared to that from the use of mupirocin in vitro. Because antibodies may affect enzyme function, we tested antibodies developed after repeated ClyS exposure for their effect on ClyS killing ability. Our results showed no inhibition of ClyS activity at various antibody titers. These data demonstrate the potential of developing ClyS as a novel class of topical antimicrobial agents specific to staphylococcus. PMID:21098252

  12. Cutaneous Immune Defenses Against Staphylococcus aureus Infections

    PubMed Central

    Choi, Ji Hae; Seo, Ho Seong; Lim, Sang Young; Park, Kyungho

    2014-01-01

    Staphylococcus aureus (S. aureus) is a virulent bacterium that abundantly colonizes inflammatory skin diseases. Since S. aureus infections occur in an impaired skin barrier, it is important to understand the protective mechanism through cutaneous immune responses against S. aureus infections and the interaction with Staphylococcal virulence factors. In this review, we summarize not only the pathogenesis and key elements of S. aureus skin infections, but also the cutaneous immune system against its infections and colonization. The information obtained from this area may provide the groundwork for further immunomodulatory therapies or vaccination strategies to prevent S. aureus infections. PMID:26064853

  13. Noninvasive In Vivo Imaging to Evaluate Immune Responses and Antimicrobial Therapy against Staphylococcus aureus and USA300 MRSA Skin Infections

    PubMed Central

    Cho, John S.; Zussman, Jamie; Donegan, Niles P.; Irene Ramos, Romela; Garcia, Nairy C.; Uslan, Daniel Z.; Iwakura, Yoichiro; Simon, Scott I.; Cheung, Ambrose L.; Modlin, Robert L.; Kim, Jenny; Miller, Lloyd S.

    2011-01-01

    Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies. PMID:21191403

  14. LL-37-Derived Peptides Eradicate Multidrug-Resistant Staphylococcus aureus from Thermally Wounded Human Skin Equivalents

    PubMed Central

    de Breij, Anna; Chan, Heelam; van Dissel, Jaap T.; Drijfhout, Jan W.; Hiemstra, Pieter S.; El Ghalbzouri, Abdoelwaheb; Nibbering, Peter H.

    2014-01-01

    Burn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistant Staphylococcus aureus (MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains of S. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria. PMID:24841266

  15. LL-37-derived peptides eradicate multidrug-resistant Staphylococcus aureus from thermally wounded human skin equivalents.

    PubMed

    Haisma, Elisabeth M; de Breij, Anna; Chan, Heelam; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; El Ghalbzouri, Abdoelwaheb; Nibbering, Peter H

    2014-08-01

    Burn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistant Staphylococcus aureus (MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains of S. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria. PMID:24841266

  16. Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections

    PubMed Central

    2013-01-01

    Background Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. Results A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). Conclusions This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin. PMID:23924370

  17. Devastating renal outcome caused by skin infection with methicillin-resistant Staphylococcus aureus

    PubMed Central

    Liang, Jun-Hua; Fang, Yu-Wei; Yang, An-Hung; Tsai, Ming Hsien

    2016-01-01

    Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen that infects the skin and soft tissue. However, there are few reports of renal complications from MRSA involving immunoglobulin (Ig)A-dominated rapidly progressive glomerulonephritis (GN). Favorable renal outcomes from IgA GN are achieved by administering timely therapy. In the present study, we describe the case of a healthy young woman suffering from a cutaneous MRSA infection that initially presented with gross hematuria. Six months after eradicating the infection, severe impairment of renal function was noted because of intractable nausea and vomiting. Renal pathology revealed advanced IgA nephropathy with fibrocellular crescent formation. An aggressive treatment plan using immunosuppressants was not adopted because of her irreversible renal pathology, and she was therefore administered maintenance hemodialysis. This instructive case stresses the importance of being aware of the signs of IgA nephropathy post-MRSA infection, such as cutaneous lesions that are mostly painless and accompanied by hematuria and mild proteinuria. If the kidney cannot be salvaged, it will undergo irreversible damage with devastating consequences. PMID:27368023

  18. Staphylococcus aureus Skin Infection Recurrences Among Household Members: An Examination of Host, Behavioral, and Pathogen-Level Predictors

    PubMed Central

    Miller, Loren G.; Eells, Samantha J.; David, Michael Z.; Ortiz, Nancy; Taylor, Alexis R.; Kumar, Neha; Cruz, Denise; Boyle-Vavra, Susan; Daum, Robert S.

    2015-01-01

    Background. Many patients suffer from recurrent Staphylococcus aureus infections, but there are few data examining recurrence predictors. Methods. We followed adults and children after treatment for S. aureus skin infections and their household contacts in Los Angeles and Chicago. We surveyed subjects for S. aureus body colonization, household fomite contamination, and behavioral and clinical factors at baseline and 3 and 6 months later. Using repeated measures modeling, we examined host, pathogen, behavioral, and clinical factors associated with recurrence. Results. Among 330 index subjects, 182 (55%) were infected with an isolate of the USA300 methicillin-resistant S. aureus (MRSA) genetic background. Recurrences occurred in 39% by month 3 and 51% by month 6. Among 588 household contacts, 10% reported a skin infection by month 3 and 13% by month 6. Among index subjects, recurrence was associated with (P < .05) Los Angeles site, diabetes, recent hospitalization, recent skin infection, recent cephalexin use, and household S. aureus or MRSA fomite contamination; recurrence was inversely associated with recent contact sports participation. In the multivariate model, independent predictors of recurrence in index patients were recent hospitalization, household MRSA fomite contamination, and lack of recent contact sports participation. Among household contacts, independent predictors of subsequent skin infection were Chicago site, antibiotic use in the prior year, and skin infection in the prior 3 months. Conclusions. In our longitudinal study, patients with a S. aureus skin infection were more likely to suffer a recurrence if household fomites were MRSA contaminated. Interventions to prevent recurrence may be enhanced by decontamination of household fomites. PMID:25428411

  19. Staphylococcus aureus biofilms

    PubMed Central

    Archer, Nathan K; Mazaitis, Mark J; Costerton, J William; Leid, Jeff G; Powers, Mary Elizabeth

    2011-01-01

    Increasing attention has been focused on understanding bacterial biofilms and this growth modality's relation to human disease. In this review we explore the genetic regulation and molecular components involved in biofilm formation and maturation in the context of the Gram-positive cocci, Staphylococcus aureus. In addition, we discuss diseases and host immune responses, along with current therapies associated with S. aureus biofilm infections and prevention strategies. PMID:21921685

  20. Evaluation of a nisin-eluting nanofiber scaffold to treat Staphylococcus aureus-induced skin infections in mice.

    PubMed

    Heunis, Tiaan D J; Smith, Carine; Dicks, Leon M T

    2013-08-01

    Staphylococcus aureus is a virulent pathogen and a major causative agent of superficial and invasive skin and soft tissue infections (SSSTIs). Antibiotic resistance in S. aureus, among other bacterial pathogens, has rapidly increased, and this is placing an enormous burden on the health care sector and has serious implications for infected individuals, especially immunocompromised patients. Alternative treatments thus need to be explored to continue to successfully treat infections caused by S. aureus, including antibiotic-resistant strains of S. aureus. In this study, an antimicrobial nanofiber wound dressing was generated by electrospinning nisin (Nisaplin) into poly(ethylene oxide) and poly(d,l-lactide) (50:50) blend nanofibers. Active nisin diffused from the nanofiber wound dressings for at least 4 days in vitro, as shown by consecutive transfers onto plates seeded with strains of methicillin-resistant S. aureus (MRSA). The nisin-containing nanofiber wound dressings significantly reduced S. aureus Xen 36 bioluminescence in vivo and viable cell numbers in a murine excisional skin infection model. The bacterial burden of wounds treated with nisin-containing nanofiber wound dressings was 4.3 × 10(2) CFU/wound, whereas wounds treated with control nanofiber wound dressings had 2.2 × 10(7) CFU/wound on the last day of the trial (day 7). Furthermore, the wound dressings stimulated wound closure of excisional wounds, and no adverse effects were observed by histological analysis. Nisin-containing nanofiber wound dressings have the potential to treat S. aureus skin infections and to potentially accelerate wound healing of excisional wounds. PMID:23733456

  1. Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

    PubMed Central

    Heunis, Tiaan D. J.; Smith, Carine

    2013-01-01

    Staphylococcus aureus is a virulent pathogen and a major causative agent of superficial and invasive skin and soft tissue infections (SSSTIs). Antibiotic resistance in S. aureus, among other bacterial pathogens, has rapidly increased, and this is placing an enormous burden on the health care sector and has serious implications for infected individuals, especially immunocompromised patients. Alternative treatments thus need to be explored to continue to successfully treat infections caused by S. aureus, including antibiotic-resistant strains of S. aureus. In this study, an antimicrobial nanofiber wound dressing was generated by electrospinning nisin (Nisaplin) into poly(ethylene oxide) and poly(d,l-lactide) (50:50) blend nanofibers. Active nisin diffused from the nanofiber wound dressings for at least 4 days in vitro, as shown by consecutive transfers onto plates seeded with strains of methicillin-resistant S. aureus (MRSA). The nisin-containing nanofiber wound dressings significantly reduced S. aureus Xen 36 bioluminescence in vivo and viable cell numbers in a murine excisional skin infection model. The bacterial burden of wounds treated with nisin-containing nanofiber wound dressings was 4.3 × 102 CFU/wound, whereas wounds treated with control nanofiber wound dressings had 2.2 × 107 CFU/wound on the last day of the trial (day 7). Furthermore, the wound dressings stimulated wound closure of excisional wounds, and no adverse effects were observed by histological analysis. Nisin-containing nanofiber wound dressings have the potential to treat S. aureus skin infections and to potentially accelerate wound healing of excisional wounds. PMID:23733456

  2. Staphylococcus aureus and Pregnancy

    MedlinePlus

    ... known as “methicillin resistance to staphylococcus aureus” or “MRSA”. Other medications are available for treatment in this situation. What will a staph or MRSA skin infection look like? Staph bacterial infections, including ...

  3. Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection

    PubMed Central

    Zhao, Fan; Chong, Anita S.; Montgomery, Christopher P.

    2016-01-01

    Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI) elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral immunity and the IgG-binding proteins Sbi and SpA in S. aureus SSTI. We found that B lymphocyte-deficient μMT mice were highly susceptible to infection, compared with congenic BALB/c mice. Importantly, transfer of immune serum protected μMT mice, demonstrating an appropriate response to protective antibody. We found that deletion of sbi, but not spa, impaired virulence, as assessed by skin lesion severity, and that Sbi-mediated virulence required B lymphocytes/antibody. Furthermore, neither Sbi nor SpA impaired the elicited antibody response or protection against secondary SSTI. Taken together, these findings highlight a B lymphocyte/antibody-dependent role of Sbi in the pathogenesis of S. aureus SSTI, and demonstrate that neither Sbi nor SpA interfered with elicited antibody-mediated immunity. PMID:26828524

  4. Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection.

    PubMed

    Zhao, Fan; Chong, Anita S; Montgomery, Christopher P

    2016-01-01

    Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI) elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral immunity and the IgG-binding proteins Sbi and SpA in S. aureus SSTI. We found that B lymphocyte-deficient μMT mice were highly susceptible to infection, compared with congenic BALB/c mice. Importantly, transfer of immune serum protected μMT mice, demonstrating an appropriate response to protective antibody. We found that deletion of sbi, but not spa, impaired virulence, as assessed by skin lesion severity, and that Sbi-mediated virulence required B lymphocytes/antibody. Furthermore, neither Sbi nor SpA impaired the elicited antibody response or protection against secondary SSTI. Taken together, these findings highlight a B lymphocyte/antibody-dependent role of Sbi in the pathogenesis of S. aureus SSTI, and demonstrate that neither Sbi nor SpA interfered with elicited antibody-mediated immunity. PMID:26828524

  5. Staphylococcus aureus skin and soft tissue infections in primary healthcare in Denmark: a 12-year population-based study.

    PubMed

    Dalager-Pedersen, M; Søgaard, M; Schønheyder, H C

    2011-08-01

    A rise in community-onset Staphylococcus aureus infections has been observed in European countries. To ascertain secular trends of S. aureus infections in primary healthcare in Denmark, we conducted this register-based study in the North Denmark region, during the period 1997-2008. We identified all skin and mucosa specimens obtained by general practitioners and all prescriptions for the preferred oral anti-staphylococcal antibiotic, dicloxacillin. Repeat observations within a 12-month period were excluded prior to the calculation of age and gender standardised incidence rates per 100,000 person-years. We included 108,758 specimens, of which 42,778 (39%) yielded S. aureus. The annual incidence rate of specimens doubled during the study period, reaching 2,399 in 2008. The overall rate of S. aureus isolates increased 2-fold to a stable rate at about 850, but for isolates from children and for impetigo specimens, the increase was steeper, with a peak in 2002. A total of 156,462 dicloxacillin prescriptions had been redeemed and the annual prescription rate increased 2.5-fold, peaking at 3,714 in 2007. In conclusion, the annual rates of specimens, S. aureus infections and dicloxacillin prescriptions more than doubled in primary healthcare during the 12-year study period. A major impetigo epidemic and calls for antibiotic stewardship with increased utilisation of specimens were contributing factors. PMID:21279531

  6. Characterization of Staphylococcus aureus Isolated from Non-Native Patients with Skin and Soft Tissue Infections in Shanghai

    PubMed Central

    Yang, Hai-Hui; Zhu, Yue-Qiu; Guo, Xiao-Kui; Ni, Yu-Xing; Han, Li-Zhong

    2015-01-01

    Background Staphylococcus aureus is one predominant cause of skin and soft-tissue infections (SSTIs), but little information exists regarding the characterization of S. aureus from non-native patients with SSTIs in China. Methods In this study, we enrolled 52 non-native patients with S. aureus SSTIs, and 65 native control patients with S. aureus SSTIs in Shanghai. 52 and 65 S. aureus isolates were collected from both groups, respectively. S. aureus isolates were characterized by antimicrobial susceptibility testing, toxin gene detection, and molecular typing with sequence type, spa type, agr group and SCCmec type. Results Methicillin-resistant S. aureus (MRSA) was detected in 8 non-native patients and 14 native patients with SSTIs. Overall, antimicrobial susceptibilities of S. aureus isolated from non-native patients were found higher than those from native patients. CC59 (ST338 and ST59) was found in a total of 14 isolates (4 from non-native patients; 10 from native patients), 9 of which were carrying lukS/F-PV (3 from non-native patients; 6 from native patients). ST7 was found in 12 isolates and all 12 isolates were found in native patients. The livestock-associated clone ST398 was found in 11 isolates (6 from non-native patients; 5 from native patients), and 5 ST398 lukS/F-PV-positive methicillin-susceptible S. aureus (MSSA) were all discovered among non-native patients. The molecular epidemiology of S. aureus isolated from non-native patients was quite different from those from native patients. lukS/F-PV was more frequent in isolates originating from non-native patients with SSTIs compared to native patients (31 vs. 7, P <0.0001). Conclusions CC59 was the most common clonal complex among patients with SSTIs in Shanghai. The other most common sequence types were ST7 and Livestock ST398. The molecular epidemiology of S. aureus isolated from non-native patients was quite different from those from native patients. S. aureus isolated from non-native patients was

  7. Active Immunization with an Octa-Valent Staphylococcus aureus Antigen Mixture in Models of S. aureus Bacteremia and Skin Infection in Mice

    PubMed Central

    van den Berg, Sanne; Koedijk, Dennis G. A. M.; Back, Jaap Willem; Neef, Jolanda; Dreisbach, Annette; van Dijl, Jan Maarten; Bakker-Woudenberg, Irma A. J. M.; Buist, Girbe

    2015-01-01

    Proteomic studies with different Staphylococcus aureus isolates have shown that the cell surface-exposed and secreted proteins IsaA, LytM, Nuc, the propeptide of Atl (pro-Atl) and four phenol-soluble modulins α (PSMα) are invariantly produced by this pathogen. Therefore the present study was aimed at investigating whether these proteins can be used for active immunization against S. aureus infection in mouse models of bacteremia and skin infection. To this end, recombinant His-tagged fusions of IsaA, LytM, Nuc and pro-Atl were isolated from Lactococcus lactis or Escherichia coli, while the PSMα1-4 peptides were chemically synthesized. Importantly, patients colonized by S. aureus showed significant immunoglobulin G (IgG) responses against all eight antigens. BALB/cBYJ mice were immunized subcutaneously with a mixture of the antigens at day one (5 μg each), and boosted twice (25 μg of each antigen) with 28 days interval. This resulted in high IgG responses against all antigens although the response against pro-Atl was around one log lower compared to the other antigens. Compared to placebo-immunized mice, immunization with the octa-valent antigen mixture did not reduce the S. aureus isolate P load in blood, lungs, spleen, liver, and kidneys in a bacteremia model in which the animals were challenged for 14 days with a primary load of 3 × 105 CFU. Discomfort scores and animal survival rates over 14 days did not differ between immunized mice and placebo-immunized mice upon bacteremia with S. aureus USA300 (6 × 105 CFU). In addition, this immunization did not reduce the S. aureus isolate P load in mice with skin infection. These results show that the target antigens are immunogenic in both humans and mice, but in the used animal models do not result in protection against S. aureus infection. PMID:25710376

  8. The role of primary care prescribers in the diagnosis and management of community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

    PubMed

    Lawrence, Kenneth R; Golik, Monica V; Davidson, Lisa

    2009-01-01

    Nosocomial infections caused by methicillin-resistant Staphylococcus aureus were first reported in the United States in the early 1960s. Beginning in the 1990s, healthy individuals from the community with no risk factors for resistant bacteria began presenting with methicillin-resistant Staphylococcus aureus infections, acquiring the name "community-associated methicillin-resistant Staphylococcus aureus" (CA-MRSA). CA-MRSA has a tendency to affect the skin and skin structures, generally in the form of abscesses and furuncles, carbuncles, and cellulitis. Cases of invasive infections including bacteremia, endocarditis, and necrotizing pneumonia have also been reported. A patient complaint of a "spider bite" is frequently associated with CA-MRSA. CA-MRSA and the traditional health care-associated methicillin-resistant Staphylococcus aureus are distinguished by their genetic composition, virulence factors, and susceptibility patterns to non-beta-lactam antibiotics. Appropriate management of CA-MRSA skin and skin structure infections includes incision and drainage of infected tissue and appropriate antimicrobial therapy. It has been suggested that when prevalence of CA-MRSA within a community eclipses 10%-15%, empiric use of non-beta-lactam antibiotics with in vitro activity against CA-MRSA be initiated when treating skin and skin structure infections. CA-MRSA retains susceptibility to a range of older antibiotics available in oral formulations such as minocycline, doxycycline, sulfamethoxazole-trimethoprim, moxifloxacin, levofloxacin, and clindamycin. Local susceptibility patterns and individual patient factors should guide the selection of antibiotics. PMID:19617720

  9. The Staphylococcus aureus proteome.

    PubMed

    Otto, Andreas; van Dijl, Jan Maarten; Hecker, Michael; Becher, Dörte

    2014-03-01

    Staphylococcus aureus is a Gram-positive commensal bacterium that is regarded as a major threat for modern health care systems. This relates both to the ability of S. aureus to overcome antibiotic therapy by developing high-level resistance against multiple antibiotics and this bacterium's extensive arsenal of virulence factors. Understanding the mechanisms of resistance and functional studies on stress and starvation responses are the main goals of proteomics in staphylococcal research. This review high-lights recent advances in gel-based and gel-free proteomics analyses of S. aureus and pinpoints the importance of location-specific proteomics studies targeting the cytosol, the membrane, the cell surface and the extracellular milieu in combination with integrated global proteome studies. Emerging hot topics in staphylococcal proteomics are discussed with special focus on in vivo proteomics, membrane vesicles, biofilm formation and the acquisition of absolute proteome data for systems biological modeling approaches. PMID:24439828

  10. Mannitol Utilisation is Required for Protection of Staphylococcus aureus from Human Skin Antimicrobial Fatty Acids

    PubMed Central

    Kolar, Stacey L.; Ulanov, Alexander; Li, Zhong; Shaw, Lindsey N.; Josefsson, Elisabet; Horsburgh, Malcolm J.

    2013-01-01

    Mannitol (Mtl) fermentation, with the subsequent production of acid, is a species signature of Staphylococcus aureus, and discriminates it from most other members of the genus. Inactivation of the gene mtlD, encoding Mtl-1-P dehydrogenase was found to markedly reduce survival in the presence of the antimicrobial fatty acid, linoleic acid. We demonstrate that the sugar alcohol has a potentiating action for this membrane-acting antimicrobial. Analysis of cellular metabolites revealed that, during exponential growth, the mtlD mutant accumulated high levels of Mtl and Mtl-P. The latter metabolite was not detected in its isogenic parent strain or a deletion mutant of the entire mtlABFD operon. In addition, the mtlD mutant strain exhibited a decreased MIC for H2O2, however virulence was unaffected in a model of septic arthritis. PMID:23861785

  11. Proteomic Identification of saeRS-Dependent Targets Critical for Protective Humoral Immunity against Staphylococcus aureus Skin Infection.

    PubMed

    Zhao, Fan; Cheng, Brian L; Boyle-Vavra, Susan; Alegre, Maria-Luisa; Daum, Robert S; Chong, Anita S; Montgomery, Christopher P

    2015-09-01

    Recurrent Staphylococcus aureus skin and soft tissue infections (SSTIs) are common despite detectable antibody responses, leading to the belief that the immune response elicited by these infections is not protective. We recently reported that S. aureus USA300 SSTI elicits antibodies that protect against recurrent SSTI in BALB/c but not C57BL/6 mice, and in this study, we aimed to uncover the specificity of the protective antibodies. Using a proteomic approach, we found that S. aureus SSTI elicited broad polyclonal antibody responses in both BALB/c and C57BL/6 mice and identified 10 S. aureus antigens against which antibody levels were significantly higher in immune BALB/c serum. Four of the 10 antigens identified are regulated by the saeRS operon, suggesting a dominant role for saeRS in protection. Indeed, infection with USA300Δsae failed to protect against secondary SSTI with USA300, despite eliciting a strong polyclonal antibody response against antigens whose expression is not regulated by saeRS. Moreover, the antibody repertoire after infection with USA300Δsae lacked antibodies specific for 10 saeRS-regulated antigens, suggesting that all or a subset of these antigens are necessary to elicit protective immunity. Infection with USA300Δhla elicited modest protection against secondary SSTI, and complementation of USA300Δsae with hla restored protection but incompletely. Together, these findings support a role for both Hla and other saeRS-regulated antigens in eliciting protection and suggest that host differences in immune responses to saeRS-regulated antigens may determine whether S. aureus infection elicits protective or nonprotective immunity against recurrent infection. PMID:26169277

  12. Surveillance of Physician-Diagnosed Skin and Soft Tissue Infections Consistent With Methicillin-Resistant "Staphylococcus aureus" (MRSA) among Nebraska High School Athletes, 2008-2012

    ERIC Educational Resources Information Center

    Buss, Bryan F.; Connolly, Susan

    2014-01-01

    Though historically confined to hospital settings, methicillin-resistant Staphylococcus aureus (MRSA) has received increasing attention in the wider community, particularly among athletes. A 2007-2008 investigation in Nebraska concluded that MRSA skin infections were an emerging problem among the state's student athletes. Statewide…

  13. Antimicrobial Synergic Effect of Allicin and Silver Nanoparticles on Skin Infection Caused by Methicillin-Resistant Staphylococcus aureus spp

    PubMed Central

    Sharifi-Rad, J; Hoseini Alfatemi, SM; Sharifi Rad, M; Iriti, M

    2014-01-01

    Background: Today, the commonly used antibiotics may more and more frequently be ineffective against multiple pathogens, due to the selection of resistant microbial strains. As a result, an effort to find a new approach for solving this issue has been considered. Aim: The aim of this study is to investigate antimicrobial properties of allicin, silver nanoparticles (Ag NPs) and their combination again skin infection caused by methicillin-resistant Staphylococcus aureus (MRSA) strains in an animal model. Materials and Methods: In vivo, the effects of allicin, Ag NPs and their combination were investigated on mice in which the skin infection was caused by MRSA strains. In animals, S. aureus colony-forming units (CFU)/mL were counted the 4th day after treatment. In vitro, minimum inhibitory concentration (MIC) of bacterial growth and minimum bactericidal concentration (MBC) of allicin, Ag NPs and their combination were determined by microdilution technique. Results: The results of in vitro assays showed that MIC of allicin and Ag NPs were 2.2 mg/mL and 5.6 mg/mL, respectively, and MBC of allicin and Ag NPs were 3.1 ppm and 7.5 ppm, respectively. However, MIC and MBC of allicin and Ag NPs together on MRSA strains were 0.4 mg/mL and 1.1 ppm, respectively. The results of in vivo tests on skin infection showed that bacteria counted for control, Ag NPs, allicin and their combination were 377 × 108, 80 × 106, 43 × 105, and 0 CFU/mL, respectively. Conclusion: The obtained results clearly indicated (for the first time, to the best of our knowledge) that allicin and Ag NPs, when used in combination, exhibited a synergistic activity. Therefore, the present results can be of interest in the future to improve the treatment of skin infections caused by MRSA strains. PMID:25506477

  14. Immunomodulation and Disease Tolerance to Staphylococcus aureus

    PubMed Central

    Li, Zhigang; Peres, Adam G.; Damian, Andreea C.; Madrenas, Joaquín

    2015-01-01

    The Gram-positive bacterium Staphylococcus aureus is one of the most frequent pathogens that causes severe morbidity and mortality throughout the world. S. aureus can infect skin and soft tissues or become invasive leading to diseases such as pneumonia, endocarditis, sepsis or toxic shock syndrome. In contrast, S. aureus is also a common commensal microbe and is often part of the human nasal microbiome without causing any apparent disease. In this review, we explore the immunomodulation and disease tolerance mechanisms that promote commensalism to S. aureus. PMID:26580658

  15. A comparison of available and investigational antibiotics for complicated skin infections and treatment-resistant Staphylococcus aureus and enterococcus.

    PubMed

    Scheinfeld, Noah

    2007-01-01

    This article compares vancomycin, teicoplanin, quinupristin-dalfopristin, linezolid, daptomycin, tigecyline, dalbavancin, telavancin, ceftobiprole, oritavancin, and ramoplanin for the treatment of complicated skin and skin structure infections (cSSSI), methicillin-resistant Staphylococcus aureus (MRSA), enterococcus, and vancomycin-resistant enterococcus. Vancomycin, a glycopeptide antibiotic, is administered intravenously, and is the mainstay of treatment for MRSA and cSSSI. While not available in the U.S., teicoplanin, another glycopeptide antibiotic, can be administered intramuscularly and has simpler dosing and monitoring requirements than vancomycin. Quinupristin/dalfopristin treats vancomycin-resistant Enterococcus faecium (VREF) infections but inhibits cytochrome P450 A3P4, and has only modest activity against MRSA pneumonia. Daptomycin effectively treats cSSSI but not pneumonia caused by MRSA, and is effective against all strains of Staphylococcus. Linezolid, available orally and intravenously, is approved to treat community-acquired and nosocomial pneumonia, cSSSI, and infections caused by MRSA and vancomycin-resistant enterococci including infections with concurrent bacteraemia and VREE Tigecycline, a glycylcycline derived from minocycline, has been approved by the FDA to treat cSSSI and complicated intraabdominal infections, and might be effective against Acinetobacter baumannii; its primary side effect is digestive upset. Dalbavancin, effective against MRSA and administered intravenously once weekly, possesses coverage similar to vancomycin. Telavancin deploys multiple mechanisms of action and is effective against MRSA and Gram-positive bacteria resistant to vancomycin. Ceftobiprole, a cephalosporin effective against MRSA, has few side effects. Oritavancin demonstrates similar activity to vancomycin but possesses extended activity against vancomycin-resistant Staphylococcus and enterococci. Ramoplanin, a macrocyclic depsipeptide, is unstable in the

  16. Relationship between Adherence to Oral Antibiotics and Postdischarge Clinical Outcomes among Patients Hospitalized with Staphylococcus aureus Skin Infections.

    PubMed

    Eells, Samantha J; Nguyen, Megan; Jung, Jina; Macias-Gil, Raul; May, Larissa; Miller, Loren G

    2016-05-01

    Skin and soft tissue infections are common and frequently recur. Poor adherence to antibiotic therapy may lead to suboptimal clinical outcomes. However, adherence to oral antibiotic therapy for skin and soft tissue infections and its relationship to clinical outcomes have not been examined. We enrolled adult patients hospitalized with uncomplicated skin and soft tissue infections caused by Staphylococcus aureus who were being discharged with oral antibiotics to complete therapy. We fit the participants' pill bottles with an electronic bottle cap that recorded each pill bottle opening, administered an in-person standardized questionnaire at enrollment, 14 days, and 30 days, and reviewed the participants' medical records to determine outcomes. Our primary outcome was poor clinical response, defined as a change in antibiotic therapy, new incision-and-drainage procedure, or new skin infection within 30 days of hospital discharge. Of our 188 participants, 87 had complete data available for analysis. Among these participants, 40 (46%) had a poor clinical response at 30 days. The mean electronically measured adherence to antibiotic therapy was significantly different than the self-reported adherence (57% versus 96%; P < 0.0001). In a multivariable model, poor clinical response at 30 days was associated with patients having lower adherence, being nondiabetic, and reporting a lack of illicit drug use within the previous 12 months (P < 0.05). In conclusion, we found that patient adherence to oral antibiotic therapy for a skin and soft tissue infection after hospital discharge was low (57%) and associated with poor clinical outcome. Patients commonly overstate their medication adherence, which may make identification of patients at risk for nonadherence and poor outcomes challenging. Further studies are needed to improve postdischarge antibiotic adherence after skin and soft tissue infections. PMID:26926634

  17. Chitosan-Based Film of Tyrothricin for Enhanced Antimicrobial Activity against Common Skin Pathogens Including Staphylococcus aureus.

    PubMed

    Han, Sang Duk; Sung, Hyun Jung; Lee, Ga Hyeon; Jun, Joon-Ho; Son, Miwon; Kang, Myung Joo

    2016-05-28

    Chitosan-based film-forming gel is regarded as a promising vehicle for topical delivery of antimicrobial agents to skin wounds, since it protects from microbial infection and the cationic polymer itself possesses antibacterial activity. In this study, possible synergistic interaction against common skin pathogens between the cationic polymer and tyrothricin (TRC), a cyclic polypeptide antibiotic, was investigated, by determining the concentration to inhibit 90% of bacterial isolates (MIC). The addition of the polysaccharide to TRC dramatically reduced the MIC values of TRC by 1/33 and 1/4 against both methicillin-resistant and methicillinsusceptible Staphylococcus aureus, respectively. The synergism of TRC and chitosan combination against both strains was demonstrated by the checkerboard method, with a fractional inhibitory concentration index below 0.5. Moreover, co-treatment of TRC and chitosan exhibited antibacterial activity against Pseudomonas aeruginosa, due to the antibacterial activity of chitosan, whereas TRC itself did not inhibit the gram-negative bacterial growth. These findings suggested that the use of chitosan-based film for topical delivery of TRC could be an alternative to improve TRC antimicrobial activity against strains that are abundant in skin wounds. PMID:26907760

  18. Specific Behaviors Predict Staphylococcus aureus Colonization and Skin and Soft Tissue Infections Among Human Immunodeficiency Virus-Infected Persons.

    PubMed

    Crum-Cianflone, Nancy F; Wang, Xun; Weintrob, Amy; Lalani, Tahaniyat; Bavaro, Mary; Okulicz, Jason F; Mende, Katrin; Ellis, Michael; Agan, Brian K

    2015-04-01

    Background.  Few data exist on the incidence and risk factors of Staphylococcus aureus colonization and skin and soft tissue infections (SSTIs) among patients infected with human immunodeficiency virus (HIV). Methods.  Over a 2-year period, we prospectively evaluated adults infected with HIV for incident S aureus colonization at 5 body sites and SSTIs. Cox proportional hazard models using time-updated covariates were performed. Results.  Three hundred twenty-two participants had a median age of 42 years (interquartile range, 32-49), an HIV duration of 9.4 years (2.7-17.4), and 58% were on highly active antiretroviral therapy (HAART). Overall, 102 patients (32%) became colonized with S aureus with an incidence rate of 20.6 (95% confidence interval [CI], 16.8-25.0) per 100 person-years [PYs]. Predictors of colonization in the final multivariable model included illicit drug use (hazard ratios [HR], 4.26; 95% CI, 1.33-13.69) and public gym use (HR 1.66, 95% CI, 1.04-2.66), whereas antibacterial soap use was protective (HR, 0.50; 95% CI, 0.32-0.78). In a separate model, perigenital colonization was associated with recent syphilis infection (HR, 4.63; 95% CI, 1.01-21.42). Fifteen percent of participants developed an SSTI (incidence rate of 9.4 cases [95% CI, 6.8-12.7] per 100 PYs). Risk factors for an SSTI included incident S aureus colonization (HR 2.52; 95% CI, 1.35-4.69), public shower use (HR, 2.59; 95% CI, 1.48-4.56), and hospitalization (HR 3.54; 95% CI, 1.67-7.53). The perigenital location for S aureus colonization was predictive of SSTIs. Human immunodeficiency virus-related factors (CD4 count, HIV RNA level, and HAART) were not associated with colonization or SSTIs. Conclusions.  Specific behaviors, but not HIV-related factors, are predictors of colonization and SSTIs. Behavioral modifications may be the most important strategies in preventing S aureus colonization and SSTIs among persons infected with HIV. PMID:26380335

  19. Exotoxins of Staphylococcus aureus

    PubMed Central

    Dinges, Martin M.; Orwin, Paul M.; Schlievert, Patrick M.

    2000-01-01

    This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented. PMID:10627489

  20. Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization

    PubMed Central

    Liew, Yun Khoon; Awang Hamat, Rukman; van Belkum, Alex; Chong, Pei Pei

    2015-01-01

    The exoproteome of Staphylococcus aureus contains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three different S. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios included S. aureus bacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, an N-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers. PMID:25809633

  1. RNA-Seq Analysis of the Host Response to Staphylococcus aureus Skin and Soft Tissue Infection in a Mouse Model

    PubMed Central

    Brady, Rebecca A.; Bruno, Vincent M.; Burns, Drusilla L.

    2015-01-01

    Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI), which are primarily self-limiting. We conducted a comprehensive analysis of the host transcriptome during a S. aureus SSTI to provide insight on the protective mechanisms that thwart these infections. We utilized a murine SSTI model in which one ear is epicutaneously challenged while the other is not. We then harvested these infected and uninfected ears, as well as ears from naïve mice, at one, four, and seven days post-challenge, and performed RNA sequencing (RNA-seq) using the Illumina platform. RNA-seq data demonstrated a robust response at the site of infection. Comparison of gene expression profiles between infected ears and the non-infected ears of challenged mice defined the local response to infection, while comparisons of expression profiles of non-infected ears from challenged mice to ears of naïve mice revealed changes in gene expression levels away from the site indicative of a systemic response. Over 1000 genes exhibited increased expression locally at all tested time points. The local response was more robust than the systemic response. Through evaluation of the RNA-seq data using the Upstream Regulator Analytic as part of the Ingenuity Pathway Analysis software package, we found that changes in the activation and inhibition of regulatory pathways happen first locally, and lag behind systemically. The activated pathways are highly similar at all three time points during SSTI, suggesting a stable global response over time. Transcript increases and pathway activation involve pro- and anti-inflammatory mediators, chemotaxis, cell signaling, keratins, and TH1/TH17 cytokines. Transcript decreases and pathway inhibition demonstrate that metabolic genes and anti-inflammatory pathways are repressed. These data provide insight on the host responses that may aid in resolution of this self-limited S. aureus infection, and may shed light on potential immune correlates of

  2. RNA-Seq Analysis of the Host Response to Staphylococcus aureus Skin and Soft Tissue Infection in a Mouse Model.

    PubMed

    Brady, Rebecca A; Bruno, Vincent M; Burns, Drusilla L

    2015-01-01

    Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI), which are primarily self-limiting. We conducted a comprehensive analysis of the host transcriptome during a S. aureus SSTI to provide insight on the protective mechanisms that thwart these infections. We utilized a murine SSTI model in which one ear is epicutaneously challenged while the other is not. We then harvested these infected and uninfected ears, as well as ears from naïve mice, at one, four, and seven days post-challenge, and performed RNA sequencing (RNA-seq) using the Illumina platform. RNA-seq data demonstrated a robust response at the site of infection. Comparison of gene expression profiles between infected ears and the non-infected ears of challenged mice defined the local response to infection, while comparisons of expression profiles of non-infected ears from challenged mice to ears of naïve mice revealed changes in gene expression levels away from the site indicative of a systemic response. Over 1000 genes exhibited increased expression locally at all tested time points. The local response was more robust than the systemic response. Through evaluation of the RNA-seq data using the Upstream Regulator Analytic as part of the Ingenuity Pathway Analysis software package, we found that changes in the activation and inhibition of regulatory pathways happen first locally, and lag behind systemically. The activated pathways are highly similar at all three time points during SSTI, suggesting a stable global response over time. Transcript increases and pathway activation involve pro- and anti-inflammatory mediators, chemotaxis, cell signaling, keratins, and TH1/TH17 cytokines. Transcript decreases and pathway inhibition demonstrate that metabolic genes and anti-inflammatory pathways are repressed. These data provide insight on the host responses that may aid in resolution of this self-limited S. aureus infection, and may shed light on potential immune correlates of

  3. Antimicrobial susceptibility, virulence determinant carriage and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections.

    PubMed

    Yu, Fangyou; Liu, Yunling; Lv, Jinnan; Qi, Xiuqin; Lu, Chaohui; Ding, Yu; Li, Dan; Liu, Huanle; Wang, Liangxing

    2015-01-01

    A better understanding of the antimicrobial susceptibility, carriage of virulence determinants and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections (SSTIs) may provide further insights related to clinical outcomes with these infections. From January 2012 to September 2013, a total of 128 non-duplicate S. aureus isolates were recovered from patients with SSTIs. All 128 S. aureus SSTI isolates carried at least five virulence genes tested. Virulence genes detected among at least 70% of all tested isolates included hld (100%), hla (95.3%), icaA (96.9%), clf (99.2%), sdrC (79.7%), sdrD (70.3%), and sdrE (72.7%). The prevalence of MRSA isolates with 10 virulence genes tested (54.4%, 31/56) was significantly higher than that among MSSA isolates (35.2%, 25/71) (p<0.05). The positive rates of seb, sen, sem, sdrE and pvl among MRSA isolates were significantly higher than among MSSA isolates (p<0.05). ST7 and ST630 accounting for 10.9% were found to be the predominant STs. The most prevalent spa type was t091 (8.6%). MRSA-ST59-SCCmec IV was the most common clone (12.3%) among MRSA isolates whereas among MSSA isolates the dominant clone was MSSA-ST7 (15.5%). Six main clonal complexes (CCs) were found, including CC5 (52.3%), CC7 (11.7%), CC59 (8.6%), CC88 (6.3%), CC398 (4.7%), and CC121 (3.1%). A higher carriage of seb and sec was found among CC59 isolates. In comparison to CC5 and CC7 isolates, those with the highest carriage rates (>80.0%) of sdrC and sdrD, CC59 isolates had lower prevalence of these two virulence genes. All CC59 isolates were susceptible to gentamicin and trimethoprim/sulfamethoxazole, while CC5 and CC7 isolates had resistance rates to these two antimicrobials of 25.4% and 20.9%, and 40.0% and 40.0%, respectively. The resistance rates for tetracycline, clindamycin, and erythromycin among CC5 isolates were lower than among CC7 and CC59 isolates. In conclusion, the molecular typing of S. aureus SSTI

  4. Change in Antimicrobial Susceptibility of Skin-Colonizing Staphylococcus aureus in Korean Patients with Atopic Dermatitis during Ten-Year Period

    PubMed Central

    Park, Jung-Min; Jo, Ju-Hyun; Jin, Hyunju; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Jung-Min; Kim, Do-Won; Jang, Ho-Sun

    2016-01-01

    Background A small subset of adolescents atopic dermatitis (AD) tends to persist. This also leads to get more antibiotics exposure with advancing years. Antibiotic resistance has been regarded as a serious problem during Staphylococcus aureus treatment, especially methicillin-resistant S. aureus (MRSA). Objective It was investigated the S. aureus colonization frequency in the skin lesions and anterior nares of adolescent AD patients and evaluated the changes in S. aureus antimicrobial susceptibility for years. Methods Patients who visited our clinic from September 2003 to August 2005 were classified into group A, and patients who visited from August 2010 to March 2012 were classified into group B. To investigate the differences with regard to patients' age and disease duration, the patients were subdivided into groups according to age. Lesional and nasal specimens were examined. Results Among the 295 AD patients, the total S. aureus colonization rate in skin lesions was 66.9% (95/142) for group A and 78.4% (120/153) for group B. No significant changes in the systemic antimicrobial susceptibilities of S. aureus strains isolated from adolescent AD patients were observed during about 10-year period. The increased trend of MRSA isolation in recent adolescent AD outpatients suggest that the community including school could be the source of S. aureus antibiotic resistance and higher fusidic acid resistance rates provides evidence of imprudent topical use. Conclusion Relatively high MRSA isolation and fusidic acid resistance rates in recent AD patients suggest that the community harbors antibiotic-resistant S. aureus. PMID:27489430

  5. Evasion of Neutrophil Killing by Staphylococcus aureus

    PubMed Central

    McGuinness, Will A.; Kobayashi, Scott D.; DeLeo, Frank R.

    2016-01-01

    Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils), are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions. PMID:26999220

  6. Evasion of Neutrophil Killing by Staphylococcus aureus.

    PubMed

    McGuinness, Will A; Kobayashi, Scott D; DeLeo, Frank R

    2016-01-01

    Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils), are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions. PMID:26999220

  7. Utility of a single nasal polymerase chain reaction assay in predicting absence of skin and environmental contamination in hospitalized patients with past methicillin-resistant Staphylococcus aureus.

    PubMed

    Guerrero, Dubert M; Wagner, Matthew; Carson, Grace; Hanish, Christine; Thompson, Jody; Orr, Megan; Roth, Felix; Carson, Paul J

    2016-06-01

    We evaluated hospitalized patients with a history of methicillin-resistant Staphylococcus aureus (MRSA) for persistent colonization and need for contact precautions. Up to 3 daily cultures of nares, skin, and any present wounds were compared with a single nasal polymerase chain reaction (PCR) assay. Most patients (76.2%) were no longer colonized with MRSA. A single PCR assay was sufficient to exclude persistent colonization and environmental contamination and remove the contact precautions. PMID:26874408

  8. [Protein toxins of Staphylococcus aureus].

    PubMed

    Shamsutdinov, A F; Tiurin, Iu A

    2014-01-01

    Main scientific-research studies regarding protein bacterial toxins of the most widespread bacteria that belong to Staphylococcus spp. genus and in particular the most pathogenic species for humans--Staphylococcus aureus, are analyzed. Structural and biological properties of protein toxins that have received the name of staphylococcus pyrogenic toxins (PTSAg) are presented. Data regarding genetic regulation of secretion and synthesis of these toxins and 3 main regulatory genetic systems (agr--accessory gene regulator, xpr--extracellular protein regulator, sar--staphylococcal accessory regulator) that coordinate synthesis of the most important protein toxins and enzymes for virulence of S. aureus, are presented. PMID:25051707

  9. Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection

    PubMed Central

    Malachowa, Natalia; Kobayashi, Scott D.; Porter, Adeline R.; Braughton, Kevin R.; Scott, Dana P.; Gardner, Donald J.; Missiakas, Dominique M.; Schneewind, Olaf; DeLeo, Frank R.

    2016-01-01

    Staphylococcus aureus produces numerous factors that facilitate survival in the human host. S. aureus coagulase (Coa) and von Willebrand factor-binding protein (vWbp) are known to clot plasma through activation of prothrombin and conversion of fibrinogen to fibrin. In addition, S. aureus clumping factor A (ClfA) binds fibrinogen and contributes to platelet aggregation via a fibrinogen- or complement-dependent mechanism. Here, we evaluated the contribution of Coa, vWbp and ClfA to S. aureus pathogenesis in a rabbit model of skin and soft tissue infection. Compared to skin abscesses caused by the Newman wild-type strain, those caused by isogenic coa, vwb, or clfA deletion strains, or a strain deficient in coa and vwb, were significantly smaller following subcutaneous inoculation in rabbits. Unexpectedly, we found that fibrin deposition and abscess capsule formation appear to be independent of S. aureus coagulase activity in the rabbit infection model. Similarities notwithstanding, S. aureus strains deficient in coa and vwb elicited reduced levels of several proinflammatory molecules in human blood in vitro. Although a specific mechanism remains to be determined, we conclude that S. aureus Coa, vWbp and ClfA contribute to abscess formation in rabbits. PMID:27336691

  10. Antimicrobial resistance profile of Staphylococcus aureus isolates obtained from skin and soft tissue infections of outpatients from a university hospital in Recife - PE, Brazil*

    PubMed Central

    Caraciolo, Fabiana Beserra; Maciel, Maria Amélia Vieira; dos Santos, Josemir Belo; Rabelo, Marcelle Aquino; Magalhães, Vera

    2012-01-01

    BACKGROUND Staphylococcus aureus has a notable ability to acquire resistance to antibiotics, and methicillin resistance represents a growing public health problem. Methicillin-resistant S. aureus (MRSA) has also become important outside the hospital environment, particularly in the United States. In Brazil, since 2005, cases of community skin infections caused by MRSA have been reported, but resistance studies involving outpatients are scarce. OBJECTIVE To know the resistance profile of S. aureus involved in skin and soft tissue infections of patients seen at the Dermatology outpatient clinic of a university hospital in Recife, Pernambuco State, northeastern Brazil. METHODS Prospective study involving 30 patients with skin and soft tissue infections, seen at the Dermatology outpatient clinic from May until November 2011. To evaluate the susceptibility of S. aureus to antibiotics, the disk diffusion method and oxacillin screening agar were used. RESULTS From a total of 30 samples of skin lesions, 19 (63%) had positive culture for S. aureus. The following resistance patterns of S. aureus were observed: penicillin, 95%; tetracycline, 32%; erythromycin, 21%; gentamicin, 16%; cefoxitin, 11%; oxacillin, 11%; trimethoprim-sulfamethoxazole, 11%; chloramphenicol, 11%; clindamycin, 5% ; and ciprofloxacin, 0%. One of the identified MRSA was obtained from a patient without risk factors for its acquisition, and was resistant, beyond to the beta-lactams, only to tetracycline. CONCLUSIONS With regard to the resistance patterns of S. aureus, resistances to tetracycline, erythromycin and gentamicin were the highest. It was documented, for the first time in Pernambuco, a case of skin infection caused by community-associated MRSA. PMID:23197204

  11. Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City

    PubMed Central

    Pardos de la Gandara, Maria; Raygoza Garay, Juan Antonio; Mwangi, Michael; Tobin, Jonathan N.; Tsang, Amanda; Khalida, Chamanara; D'Orazio, Brianna; Kost, Rhonda G.; Leinberger-Jabari, Andrea; Coffran, Cameron; Evering, Teresa H.; Coller, Barry S.; Balachandra, Shirish; Urban, Tracie; Parola, Claude; Salvato, Scott; Jenks, Nancy; Wu, Daren; Burgess, Rhonda; Chung, Marilyn; de Lencastre, Herminia

    2015-01-01

    In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired Staphylococcus aureus strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for S. aureus were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by S. aureus: methicillin-resistant S. aureus (MRSA) was recovered from 39 wounds and methicillin-sensitive S. aureus (MSSA) was recovered from 24. Most—46 of the 63–wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL+) group of S. aureus clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with S. aureus infections, 30 were also colonized by S. aureus in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing. PMID:26063853

  12. Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City.

    PubMed

    Pardos de la Gandara, Maria; Raygoza Garay, Juan Antonio; Mwangi, Michael; Tobin, Jonathan N; Tsang, Amanda; Khalida, Chamanara; D'Orazio, Brianna; Kost, Rhonda G; Leinberger-Jabari, Andrea; Coffran, Cameron; Evering, Teresa H; Coller, Barry S; Balachandra, Shirish; Urban, Tracie; Parola, Claude; Salvato, Scott; Jenks, Nancy; Wu, Daren; Burgess, Rhonda; Chung, Marilyn; de Lencastre, Herminia; Tomasz, Alexander

    2015-08-01

    In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired Staphylococcus aureus strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for S. aureus were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by S. aureus: methicillin-resistant S. aureus (MRSA) was recovered from 39 wounds and methicillin-sensitive S. aureus (MSSA) was recovered from 24. Most-46 of the 63-wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL(+)) group of S. aureus clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with S. aureus infections, 30 were also colonized by S. aureus in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing. PMID:26063853

  13. Longitudinal Antibiotic Susceptibility Profiles of Staphylococcus aureus Cutaneous Infections in a Pediatric Outpatient Population.

    PubMed

    Slater, Nathaniel A; Gilligan, Peter H; Morrell, Dean S

    2016-09-01

    This longitudinal update on Staphylococcus aureus prevalence and antibiotic resistance patterns surveyd 291 cultures from 188 patients in a pediatric outpatient dermatology clinic with suspected skin and soft tissue infections. The prevalence of methicillin-resistant Staphylococcus aureus remained stable at 24%. Staphylococcus aureus resistance to tetracyclines modestly but demonstrably increased in the interval since 2009. PMID:27384814

  14. Skin Barrier Function and Staphylococcus aureus Colonization in Vestibulum Nasi and Fauces in Healthy Infants and Infants with Eczema: A Population-Based Cohort Study

    PubMed Central

    Berents, Teresa Løvold; Carlsen, Karin Cecilie Lødrup; Mowinckel, Petter; Skjerven, Håvard Ove; Kvenshagen, Bente; Rolfsjord, Leif Bjarte; Bradley, Maria; Lieden, Agne; Carlsen, Kai-Håkon; Gaustad, Peter; Gjersvik, Petter

    2015-01-01

    Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants. PMID:26070153

  15. Skin Barrier Function and Staphylococcus aureus Colonization in Vestibulum Nasi and Fauces in Healthy Infants and Infants with Eczema: A Population-Based Cohort Study.

    PubMed

    Berents, Teresa Løvold; Carlsen, Karin Cecilie Lødrup; Mowinckel, Petter; Skjerven, Håvard Ove; Kvenshagen, Bente; Rolfsjord, Leif Bjarte; Bradley, Maria; Lieden, Agne; Carlsen, Kai-Håkon; Gaustad, Peter; Gjersvik, Petter

    2015-01-01

    Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants. PMID:26070153

  16. Recurrent skin infection associated with nasal carriage of Panton-Valentine leukocidin-positive methicillin-susceptible Staphylococcus aureus closely related to the EMRSA-15 clone.

    PubMed

    Vignaroli, Carla; Di Sante, Laura; Stano, Paola; Varaldo, Pietro E; Camporese, Alessandro

    2016-01-01

    We report the case of a soldier with recurrent skin infection associated with nasal carriage of a Panton-Valentine leukocidin (PVL)-producing methicillin-susceptible Staphylococcus aureus (MSSA), closely related to the EMRSA-15 clone. MSSA isolates causing infection not requiring hospitalization usually go unnoticed; however, their typing may be useful to understand the global distribution of successful staphylococcal lineages related to epidemic clones. PVL-positive MSSA strains might serve as reservoirs from which virulent methicillin-resistant strains may evolve and spread. PMID:26674061

  17. The Zwitterionic Cell Wall Teichoic Acid of Staphylococcus aureus Provokes Skin Abscesses in Mice by a Novel CD4+ T-Cell-Dependent Mechanism

    PubMed Central

    Weidenmaier, Christopher; McLoughlin, Rachel M.; Lee, Jean C.

    2010-01-01

    Zwitterionic polysaccharide (ZPS) components of the bacterial cell envelope have been shown to exert a major histocompatibility complex (MHC) II-dependent activation of CD4+ T cells, which in turn can modulate the outcome and progression of infections in animal models. We investigated the impact of zwitterionic cell wall teichoic acid (WTA) produced by Staphylococcus aureus on the development of skin abscesses in a mouse model. We also compared the relative biological activities of WTA and capsular polysaccharide (CP), important S. aureus pathogenicity factors, in abscess formation. Expression of both WTA and CP markedly affected the ability of S. aureus to induce skin abscess formation in mice. Purified wild-type zwitterionic WTA was more active in inducing abscess formation than negatively charged mutant WTA or purified CP8. To assess the ability of purified native WTA to stimulate T cell proliferation in vitro, we co-cultivated WTA with human T-cells and antigen presenting cells in the presence and absence of various inhibitors of MHC-II presentation. Wild-type WTA induced T cell proliferation to a significantly greater extent than negatively charged WTA. T cell activation was dependent on the presentation of WTA on MHC II, since inhibitors of MHC II-dependent presentation and antibodies to MHC II significantly reduced T cell proliferation. T cells activated in vitro with wild-type WTA, but not negatively charged WTA, induced abscess formation when injected subcutaneously into wild-type mice. CD4−/− mice similarly injected with WTA failed to develop abscesses. Our results demonstrate that the zwitterionic WTA of S. aureus induces CD4+ T-cell proliferation in an MHCII-dependent manner, which in turn modulates abscess formation in a mouse skin infection model. An understanding of this novel T cell-dependent host response to staphylococcal abscess formation may lead to the development of new strategies to combat S. aureus skin and soft tissue infections. PMID

  18. [Vancomycin-resistant Staphylococcus aureus].

    PubMed

    Rodríguez, Carlos Andrés; Vesga, Omar

    2005-12-01

    The evolution and molecular mechanisms of vancomycin resistance in Staphylococcus aureus were reviewed. Case reports and research studies on biochemestry, electron microscopy and molecular biology of Staphylococcus aureus were selected from Medline database and summarized in the following review. After almost 40 years of successful treatment of S. aureus with vancomycin, several cases of clinical failures have been reported (since 1997). S. aureus strains have appeared with intermediate susceptibility (MIC 8-16 microg/ml), as well as strains with heterogeneous resistance (global MIC < or =4 microg/ml), but with subpopulations of intermediate susceptibility. In these cases, resistance is mediated by cell wall thickening with reduced cross linking. This traps the antibiotic before it reaches its major target, the murein monomers in the cell membrane. In 2002, a total vancomycin resistant strain (MIC > or =32 microg/ml) was reported with vanA genes from Enterococcus spp. These genes induce the change of D-Ala-D-Ala terminus for D-Ala-D-lactate in the cell wall precursors, leading to loss of affinity for glycopeptides. Vancomycin resistance in S. aureus has appeared; it is mediated by cell wall modifications that trap the antibiotic before it reaches its action site. In strains with total resistance, Enterococcus spp. genes have been acquired that lead to modification of the glycopeptide target. PMID:16433184

  19. Experimental Staphylococcus aureus brain abscess.

    PubMed

    Enzmann, D R; Britt, R R; Obana, W G; Stuart, J; Murphy-Irwin, K

    1986-01-01

    The virulent organism Staphylococcus aureus produced brain abscesses that were quantitatively and qualitatively different from those caused by less virulent organisms. S. aureus abscesses created larger lesions, as earlier ependymitis, delayed progress toward healing, and caused areas of inflammatory escape outside the collagen capsule. Imaging tests revealed similar findings: the abscesses were larger, had more extensive central necrosis, and showed earlier evidence of ependymitis. This virulent organism also demonstrated that white matter is more susceptible than overlying gray matter to destruction by infection. The pattern of spread and other histologic findings suggest that collagen capsule formation has less of an infection "containment" function than was previously thought. PMID:3085444

  20. Kinin receptor expression during Staphylococcus aureus infection

    PubMed Central

    Bengtson, Sara H.; Phagoo, Stephen B.; Norrby-Teglund, Anna; Påhlman, Lisa; Mörgelin, Matthias; Zuraw, Bruce L.; Leeb-Lundberg, L. M. Fredrik; Herwald, Heiko

    2006-01-01

    An inappropriate host response to invading bacteria is a critical parameter that often aggravates the outcome of an infection. Staphylococcus aureus is a major human Gram-positive pathogen that causes a wide array of community- and hospital-acquired diseases ranging from superficial skin infections to severe conditions such as staphylococcal toxic shock. Here we find that S aureus induces inflammatory reactions by modulating the expression and response of the B1 and B2 receptors, respectively. This process is initiated by a chain of events, involving staphylococcal-induced cytokine release from monocytes, bacteria-triggered contact activation, and conversion of bradykinin to its metabolite desArg9bradykinin. The data of the present study implicate an important and previously unknown role for kinin receptor regulation in S aureus infections. PMID:16735595

  1. A multicentre study of meticillin-resistant Staphylococcus aureus in acute bacterial skin and skin-structure infections in China: susceptibility to ceftaroline and molecular epidemiology.

    PubMed

    Zhang, Hui; Xiao, Meng; Kong, Fanrong; O'Sullivan, Matthew V N; Mao, Lei-Li; Zhao, Hao-Ran; Zhao, Ying; Wang, He; Xu, Ying-Chun

    2015-04-01

    Ceftaroline is a novel cephalosporin with activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to investigate the susceptibility to ceftaroline of hospital-associated MRSA (HA-MRSA) isolates causing acute bacterial skin and skin-structure infections (ABSSSIs) in China and to examine their relationship by genotyping. A total of 251 HA-MRSA isolates causing ABSSSIs were collected from a multicentre study involving 56 hospitals in 38 large cities across 26 provinces in mainland China. All isolates were characterised by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, spa typing and detection of the Panton-Valentine leukocidin locus (lukS-PV and lukF-PV). Minimum inhibitory concentrations (MICs) of 14 antimicrobial agents, including ceftaroline, were determined by broth microdilution and were interpreted using Clinical and Laboratory Standards Institute breakpoints. The ceftaroline MIC50 and MIC90 values (MICs that inhibit 50% and 90% of the isolates, respectively) were 1 μg/mL and 2 μg/mL, respectively; 33.5% (n=84) of the isolates studied were ceftaroline-non-susceptible, with MICs of 2 μg/mL, but no isolate exhibited ceftaroline resistance (MIC>2 μg/mL). All of the ceftaroline-non-susceptible isolates belonged to the predominant HA-MRSA clones: 95.2% (n=80) from MLST clonal complex 8 (CC8), with the remaining 4.8% (n=4) from CC5. The high rate of non-susceptibility to ceftaroline amongst HA-MRSA causing ABSSSIs in China is concerning. PMID:25649348

  2. Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

    PubMed Central

    López Furst, María José; de Vedia, Lautaro; Fernández, Silvina; Gardella, Noella; Ganaha, María Cristina; Prieto, Sergio; Carbone, Edith; Lista, Nicolás; Rotryng, Flavio; Morera, Graciana I.; Mollerach, Marta; Stryjewski, Martín E.

    2013-01-01

    Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Materials and Methods Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires) between March 2010 and October 2011. Patients were included if they were ≥14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina. PMID:24324543

  3. Cost comparison of linezolid versus vancomycin for treatment of complicated skin and skin-structure infection caused by methicillin-resistant Staphylococcus aureus in Quebec

    PubMed Central

    Pettigrew, Martine; Thirion, Daniel JG; Libman, Michael; Zanotti, Giovanni

    2012-01-01

    BACKGROUND: In Canada, complicated skin and skin-structure infection (cSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) is usually treated with antibiotics in hospital, with a follow-up course at home for stable patients. The cost implications of using intravenous and oral linezolid instead of intravenous vancomycin in Canadian clinical practice have not been examined. OBJECTIVES: To evaluate the potential treatment cost impact for the Quebec health care system of linezolid versus vancomycin for MRSA-related cSSSI therapy, using a net impact analysis approach. METHODS: Health care resource use associated with linezolid and vancomycin therapy was estimated for patients in Quebec, based on expert opinion. Costs were assigned to health care resources (antibiotics, medical supplies, laboratory testing and health care professional time) based on unit prices. The base-case analysis assumed 14 days of antibiotic treatment for both agents; five days in hospital followed by nine days at home. Therapy duration, length of inpatient treatment and discharge rates were varied in sensitivity analyses. RESULTS: Antibiotic costs were higher for linezolid than for vancomycin, for both inpatient ($874 versus $144, respectively) and outpatient therapy ($1,356 versus $1,242, respectively). Compared with vancomycin, lower costs for antibiotic preparation, administration and monitoring of linezolid offset drug acquisition costs. Total treatment costs were $3,850 for linezolid versus $5,189 for vancomycin. Results were sensitive to the number of treatment days spent at home and the discharge rate. CONCLUSION: Using linezolid instead of vancomycin to treat MRSA-related cSSSI, for hospital and home courses combined, may reduce health care resource utilization and costs in Quebec. PMID:24294273

  4. Vaccination Against Staphylococcus aureus Pneumonia

    PubMed Central

    Spaulding, Adam R.; Salgado-Pabón, Wilmara; Merriman, Joseph A.; Stach, Christopher S.; Ji, Yinduo; Gillman, Aaron N.; Peterson, Marnie L.; Schlievert, Patrick M.

    2014-01-01

    Background. Staphylococcus aureus causes serious infections in both hospital and community settings. Attempts have been made to prevent human infection through vaccination against bacterial cell-surface antigens; thus far all have failed. Here we show that superantigens and cytolysins, when used in vaccine cocktails, provide protection from S. aureus USA100–USA400 intrapulmonary challenge. Methods. Rabbits were actively vaccinated (wild-type toxins or toxoids) or passively immunized (hyperimmune serum) against combinations of superantigens (toxic shock syndrome toxin 1, enterotoxins B and C, and enterotoxin-like X) and cytolysins (α-, β-, and γ-toxins) and challenged intrapulmonarily with multiple strains of S. aureus, both methicillin-sensitive and methicillin-resistant. Results. Active vaccination against a cocktail containing bacterial cell-surface antigens enhanced disease severity as tested by infective endocarditis. Active vaccination against secreted superantigens and cytolysins resulted in protection of 86 of 88 rabbits when challenged intrapulmonarily with 9 different S. aureus strains, compared to only 1 of 88 nonvaccinated animals. Passive immunization studies demonstrated that production of neutralizing antibodies was an important mechanism of protection. Conclusions. The data suggest that vaccination against bacterial cell-surface antigens increases disease severity, but vaccination against secreted virulence factors provides protection against S. aureus. These results advance our understanding of S. aureus pathogenesis and have important implications in disease prevention. PMID:24357631

  5. Ceftaroline-Heteroresistant Staphylococcus aureus

    PubMed Central

    Saravolatz, Stephanie N.; Martin, Hayley; Pawlak, Joan; Johnson, Leonard B.

    2014-01-01

    Heteroresistance refers to the presence, within a large population of antimicrobial-susceptible microorganisms, of subpopulations with lesser susceptibilities. Ceftaroline is a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to detect the prevalence of ceftaroline heteroresistance in vitro in a select group of S. aureus strains. There were 57 isolates selected for evaluation, 20 MRSA, 20 vancomycin-intermediate S. aureus (VISA), 7 daptomycin-nonsusceptible S. aureus (DNSSA), 6 linezolid-nonsusceptible S. aureus (LNSSA), and 4 heteroresistant VISA (hVISA) isolates. MICs and minimal bactericidal concentrations were determined using the broth microdilution method according to CLSI guidelines. All of the isolates were analyzed by pulsed-field gel electrophoresis. The staphylococcal cassette chromosome mec element (SCCmec) types were determined by a multiplex PCR. Population analysis profiles (PAPs) were performed to determine heteroresistance for all of the isolates using plates made by adding various amounts of ceftaroline to brain heart infusion agar. The frequencies of resistant subpopulations were 1 in 104 to 105 organisms. We determined that 12 of the 57 (21%) isolates tested were ceftaroline-heteroresistant S. aureus (CHSA). CHSA occurred among strains with reduced susceptibilities to vancomycin, daptomycin, and linezolid but occurred in none of the USA-300 isolates tested. Evaluation of the heteroresistant strains demonstrated that the phenotype was unstable. Further studies are needed to determine whether CHSA has a role in clinical failures and to determine the implications of our study findings. PMID:24637680

  6. The association between bedding material and the bacterial counts of Staphylococcus aureus, Streptococcus uberis and coliform bacteria on teat skin and in teat canals in lactating dairy cattle.

    PubMed

    Paduch, Jan-Hendrik; Mohr, Elmar; Krömker, Volker

    2013-05-01

    Several mastitis-causing pathogens are able to colonize the bovine teat canal. The objective of this study was to investigate the association between the treatment of sawdust bedding with a commercial alkaline conditioner and the bacterial counts on teat skin and in the teat canal. The study used a crossover design. Ten lactating Holstein cows that were free of udder infections and mastitis were included in the study. The animals were bedded on either untreated sawdust or sawdust that had been treated with a hydrated lime-based conditioner. Once a day, fresh bedding material was added. After 3 weeks, the bedding material was removed from the cubicles, fresh bedding material was provided, and the cows were rotated between the two bedding material groups. Teat skin and teat canals were sampled using the wet and dry swab technique after weeks 1, 2, 3, 4, 5 and 6. Staphylococcus aureus, Streptococcus uberis, Escherichia coli and other coliform bacteria were detected in the resulting agar plate cultures. The treatment of the bedding material was associated with the teat skin bacterial counts of Str. uberis, Esch. coli and other coliform bacteria. An association was also found between the bedding material and the teat canal bacterial counts of coliform bacteria other than Esch. coli. For Staph. aureus, no associations with the bedding material were found. In general, the addition of a hydrated lime-based conditioner to sawdust reduces the population sizes of environmental pathogens on teat skin and in teat canals. PMID:23445624

  7. Efficacy of topical and systemic antibiotic treatment of meticillin-resistant Staphylococcus aureus in a murine superficial skin wound infection model.

    PubMed

    Vingsbo Lundberg, Carina; Frimodt-Møller, Niels

    2013-09-01

    Meticillin-resistant Staphylococcus aureus (MRSA) is a rapidly spreading pathogen associated predominantly with skin infections. The lack of clinical evidence indicating the best treatment strategy to combat MRSA skin infections prompted us to investigate the efficacy of available treatment options in an experimental skin wound infection model in mice. Mice were treated either topically with retapamulin (1%), fusidic acid (2%) or mupirocin (2%) or systemically with linezolid (50-100 mg/kg/day) or vancomycin (50-200 mg/kg/day) twice daily for 3 days or 6 days and the total bacterial loads in the skin lesions were determined. Retapamulin, fusidic acid and mupirocin treatment for 3 days reduced the bacterial loads by 2.5, 2.9 and 2.0 log(10) CFU, respectively, and treatment for 6 days by 5.0, 4.2 and 5.1 log(10) CFU, respectively, compared with non-treated controls (P < 0.001). Systemic treatment with linezolid for 6 days reduced the bacterial loads by 1.6 log(10) CFU compared with non-treated mice (P < 0.001), whereas vancomycin treatment showed no effect on reducing the bacterial loads in infected skin lesions. These findings suggest that topical treatment with retapamulin and mupirocin is significantly more effective than systemic treatment with linezolid and vancomycin in eradicating MRSA in skin wounds. Retapamulin and mupirocin may provide an alternative to fusidic acid treatment of MRSA in skin wounds when resistance to fusidic acid is suspected. PMID:23837927

  8. Molecular characterization of Staphylococcus aureus isolates from skin and soft tissue infections samples and healthy carriers in the Central Slovenia region.

    PubMed

    Svent-Kucina, Natasa; Pirs, Mateja; Kofol, Romina; Blagus, Rok; Smrke, Dragica Maja; Bilban, Marjan; Seme, Katja

    2016-04-01

    Staphylococcus aureus is among the most important human pathogens. It is associated with different infections and is a major cause of skin and soft tissue infections (SSTIs). The aim of our study was to compare S. aureus isolates associated with SSTIs with isolates obtained from healthy carriers in the Central Slovenia region in terms of antimicrobial susceptibility, genetic diversity by clonal complex (CC)/sequence type, spa type, and by toxin gene profiling. In total, 274 S. aureus isolates were collected prospectively by culturing wound samples from 461 SSTI patients and nasal samples from 451 healthy carriers. We have demonstrated high heterogeneity in terms of CCs and spa type in both groups of isolates. The main clone among SSTI strains was Panton-Valentine leukocidin gene (pvl) positive CC121, whereas the main clone among carrier strains was CC45 carrying a large range of toxin genes. The main spa type in both groups was t091. Pvl was more frequently present in SSTI strains (31.2% SSTI vs 3.6% carrier strains) and staphylococcal enterotoxin C was more frequently present in carrier strains (1.6% SSTI vs 17.0% carrier strains). We have also demonstrated that methicillin-resistant S. aureus was a rare cause (2.8%) of SSTIs in our region. PMID:26781044

  9. Examination of hospital length of stay in Canada among patients with acute bacterial skin and skin structure infection caused by methicillin-resistant Staphylococcus aureus

    PubMed Central

    Potashman, Michele H; Stokes, Michael; Liu, Jieruo; Lawrence, Robin; Harris, Linda

    2016-01-01

    Purpose Skin infections, particularly those caused by resistant pathogens, represent a clinical burden. Hospitalization associated with acute bacterial skin and skin structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to the economic burden of the disease. This study was conducted to provide current, real-world data on hospitalization patterns for patients with ABSSSI caused by MRSA across multiple geographic regions in Canada. Patients and methods This retrospective cohort study evaluated length of stay (LOS) for hospitalized patients with ABSSSI due to MRSA diagnosis across four Canadian geographic regions using the Discharge Abstract Database. Patients with ICD-10-CA diagnosis consistent with ABSSSI caused by MRSA between January 2008 and December 2014 were selected and assigned a primary or secondary diagnosis based on a prespecified ICD-10-CA code algorithm. Results Among 6,719 patients, 3,273 (48.7%) and 3,446 (51.3%) had a primary and secondary diagnosis, respectively. Among patients with a primary or secondary diagnosis, the cellulitis/erysipelas subtype was most common. The majority of patients presented with 0 or 1 comorbid condition; the most common comorbidity was diabetes. The mean LOS over the study period varied by geographic region and year; in 2014 (the most recent year analyzed), LOS ranged from 7.7 days in Ontario to 13.4 days in the Canadian Prairie for a primary diagnosis and from 18.2 days in Ontario to 25.2 days in Atlantic Canada for a secondary diagnosis. A secondary diagnosis was associated with higher rates of continuing care compared with a primary diagnosis (10.6%–24.2% vs 4.6%–12.1%). Conclusion This study demonstrated that the mean LOS associated with ABSSSI due to MRSA in Canada was minimally 7 days. Clinical management strategies, including medication management, which might facilitate hospital discharge, have the potential to reduce hospital LOS and related economic

  10. High prevalence of methicillin resistance and PVL genes amongStaphylococcus aureus isolates from the nares and skin lesions of pediatric patients with atopic dermatitis

    PubMed Central

    Cavalcante, F.S.; Abad, E.D.; Lyra, Y.C.; Saintive, S.B.; Ribeiro, M.; Ferreira, D.C.; dos Santos, K.R.N.

    2015-01-01

    Staphylococcus aureus is highly prevalent among patients with atopic dermatitis (AD), and this pathogen may trigger and aggravate AD lesions. The aim of this study was to determine the prevalence of S. aureus in the nares of pediatric subjects and verify the phenotypic and molecular characteristics of the isolates in pediatric patients with AD. Isolates were tested for antimicrobial susceptibility, SCCmectyping, and Panton-Valentine Leukocidin (PVL) genes. Lineages were determined by pulsed-field gel electrophoresis and multilocus sequence typing (MLST). AD severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index. Among 106 patients, 90 (85%) presented S. aureus isolates in their nares, and 8 also presented the pathogen in their skin infections. Two patients had two positive lesions, making a total of 10 S. aureusisolates from skin infections. Methicillin-resistant S. aureus(MRSA) was detected in 24 (26.6%) patients, and PVL genes were identified in 21 (23.3%), including 6 (75%) of the 8 patients with skin lesions but mainly in patients with severe and moderate SCORAD values (P=0.0095). All 24 MRSA isolates were susceptible to trimethoprim/sulfamethoxazole, while 8 isolates had a minimum inhibitory concentration (MIC) to mupirocin >1024 μg/mL. High lineage diversity was found among the isolates including USA1100/ST30, USA400/ST1, USA800/ST5, ST83, ST188, ST718, ST1635, and ST2791. There was a high prevalence of MRSA and PVL genes among the isolates recovered in this study. PVL genes were found mostly among patients with severe and moderate SCORAD values. These findings can help clinicians improve the therapies and strategies for the management of pediatric patients with AD. PMID:25992644

  11. Methicillin-resistant Staphylococcus aureus in obstetrics.

    PubMed

    Sheffield, Jeanne S

    2013-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the major multiple antibiotic-resistant bacterial pathogens causing serious community-associated and health care-associated infections. It is now pervasive in the obstetric population associated with skin and soft tissue infections, mastitis, episiotomy, and cesarean wound infections and urinary tract infections. This review addresses the epidemiology, definitions, microbiology, and pathogenesis as well as common clinical presentations. A discussion of the 2011 Infectious Diseases Society of America MRSA treatment guidelines details available antibiotics, invasive and noninvasive MRSA management, and specific factors related to obstetrics. Finally, prevention strategies including decolonization are discussed. PMID:23292915

  12. Staphylococcus aureus vaccines: Deviating from the carol.

    PubMed

    Missiakas, Dominique; Schneewind, Olaf

    2016-08-22

    Staphylococcus aureus, a commensal of the human nasopharynx and skin, also causes invasive disease, most frequently skin and soft tissue infections. Invasive disease caused by drug-resistant strains, designated MRSA (methicillin-resistant S. aureus), is associated with failure of antibiotic therapy and elevated mortality. Here we review polysaccharide-conjugate and subunit vaccines that were designed to prevent S. aureus infection in patients at risk of bacteremia or surgical wound infection but failed to reach their clinical endpoints. We also discuss vaccines with ongoing trials for combinations of polysaccharide-conjugates and subunits. S. aureus colonization and invasive disease are not associated with the development of protective immune responses, which is attributable to a large spectrum of immune evasion factors. Two evasive strategies, assembly of protective fibrin shields via coagulases and protein A-mediated B cell superantigen activity, are discussed as possible vaccine targets. Although correlates for protective immunity are not yet known, opsonophagocytic killing of staphylococci by phagocytic cells offers opportunities to establish such criteria. PMID:27526714

  13. Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Model

    PubMed Central

    Mohammad, Haroon; Cushman, Mark; Seleem, Mohamed N.

    2015-01-01

    The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections. PMID:26536129

  14. Effectiveness of Measures to Eradicate Staphylococcus aureus Carriage in Patients with Community-Associated Skin and Soft Tissue Infections: A Randomized Trial

    PubMed Central

    Fritz, Stephanie A.; Camins, Bernard C.; Eisenstein, Kimberly A.; Fritz, Joseph M.; Epplin, Emma K.; Burnham, Carey-Ann; Dukes, Jonathan; Storch, Gregory A.

    2012-01-01

    Background Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft tissue infections (SSTI). Objective Compare the effectiveness of four regimens for eradicating S. aureus carriage. Design Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at one and four months. Setting Barnes-Jewish and St. Louis Children’s Hospitals, St. Louis, Missouri, 2007–2009. Participants Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds. Interventions Participants were randomized to receive no therapeutic intervention (controls) or perform one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths. Results Among 244 participants with one-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group; 56% in the mupirocin group (p=0.03 vs. controls); 55% in the mupirocin/chlorhexidine group (p=0.05); and 63% in the mupirocin/bleach group (p=0.006). Of 229 participants with four-month colonization data, eradication rates were 48% in controls; 56% for mupirocin only (p=0.40 vs. controls); 54% for mupirocin/chlorhexidine (p=0.51); and 71% for mupirocin/bleach (p=0.02). At one and four months, respectively, recurrent SSTI was reported by 20% and 36% of participants. Conclusions An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over four months. High rates of recurrent SSTI suggest factors other than endogenous colonization as important determinants of infection. PMID:21828967

  15. Staphylococcus aureus infection of the feet following fish pedicure.

    PubMed

    Veraldi, S; Nazzaro, G; Çuka, E

    2014-10-01

    We report a case of Staphylococcus aureus infection of the feet that appeared after a "fish pedicure" (immersion of the feet in a tank with the fish Garra rufa, that nibbles off dead skin). Clinical picture was characterized by maceration, purulent discharge, scales, crusts, itching and burning sensation. Bacteriological examinations were positive for Staphylococcus aureus. Mycological examinations were negative. The patient was successfully treated with ciprofloxacin. Only one case of skin foot infection after fish pedicure was reported so far. Fish pedicure can be a potentially dangerous procedure in immunocompromised or diabetic patients. PMID:24771416

  16. Antibacterial resistance, genes encoding toxins and genetic background among Staphylococcus aureus isolated from community-acquired skin and soft tissue infections in France: a national prospective survey.

    PubMed

    Lamy, B; Laurent, F; Gallon, O; Doucet-Populaire, F; Etienne, J; Decousser, J-W

    2012-06-01

    The epidemiology of staphylococcal community-acquired skin and soft tissues infections (CA-SSTIs) has changed dramatically. We described prospectively the characteristics of the Staphylococcus aureus isolated from 71 non-teaching French hospitals and implicated in CA-SSTIs: antimicrobial susceptibility (mecA polymerase chain reaction [PCR], disk diffusion method), virulence factor gene (sea, tst, pvl) prevalence and genetic background (agr allele). During November 2006, 235 strains were collected (wound infection: 51%, abscess: 21%, whitlow: 8%, diabetic foot: 7%, furunculosis: 3%). sea, tst and pvl were identified in 22.1, 13.2 and 8.9% strains, respectively. agr allele 1 was the most frequently encountered genetic background, whatever the methicillin susceptibility. Among the 34 methicillin-resistant S. aureus (MRSA, 14.5% of all S. aureus), only one strain (2.9%) harboured pvl (belonging to the European ST80 clone), four (11.8%) tst (belonging to two endemic French clones) and 18 (52.9%) sea gene (mainly the Lyon clone). According to their in vitro activity, pristinamycin or trimethoprim/sulfamethoxazole could be considered as first-choice antibiotics. To date, the international pvl-positive MRSA clones have not spread in France. MRSA strains isolated from putative CA-SSTIs exhibited a genetic and phenotypic background of hospital-acquired (HA) clones. National survey should be continued, in order to monitor the emergence of virulent clones. PMID:21997773

  17. Improved oxacillin treatment outcomes in experimental skin and lung infection by a methicillin-resistant Staphylococcus aureus isolate with a vraSR operon deletion.

    PubMed

    Jo, Dae Sun; Montgomery, Christopher P; Yin, Shaohui; Boyle-Vavra, Susan; Daum, Robert S

    2011-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains are major pathogens causing infections of the skin and soft tissues and more serious, life-threatening diseases, including sepsis and necrotizing pneumonia. The vraSR operon encodes the key regulatory system that modulates the stress response of S. aureus elicited upon exposure to cell wall antibiotics. Mutation of vraS and vraR results in decreased oxacillin resistance in vitro. We investigated the effect of oxacillin treatment in experimental models employing a clinical USA300 MRSA strain (strain 923) and an isogenic vraSR deletion mutant (strain 923-M23). In a murine model of S. aureus necrotizing pneumonia, animals were treated with oxacillin, beginning 15 min after inoculation. Among mice infected with mutant strain 923-M23, oxacillin treatment significantly improved survival compared with saline treatment, whereas oxacillin treatment had no effect in mice infected with strain 923. Similarly, treatment with oxacillin decreased the bacterial burden among animals infected with strain 923-M23 but not among animals infected with strain 923. In a murine skin infection model, oxacillin eliminated the development of dermonecrosis among 923-M23-infected mice and decreased the bacterial burden in the lesions, but not among strain 923-infected mice. We conclude that deletion of the vraSR operon allowed an oxacillin regimen to be effective in murine models of MRSA pneumonia and skin infection. These findings provide proof-of-principle for development of a new antibiotic that could restore the usefulness of oxacillin against MRSA by inhibiting VraS or VraR. PMID:21383093

  18. Epidemiology, clinical manifestations, and treatment options for skin and soft tissue infection caused by community-acquired methicillin-resistant Staphylococcus aureus

    PubMed Central

    Farley, Jason E.

    2009-01-01

    Purpose: This article reviews the evolving epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and the appropriate outpatient management of CA-MRSA skin and soft tissue infection. Further, the paper will provide the basis upon which an individualized patient educational plan may be developed. Data Sources: To complete this review, a search of English language publications was conducted through Medline and CINAHL databases (1966–2006). Conclusions: The epidemiology of CA-MRSA is becoming increasingly complex. Research that addresses the impact of this organism in high-risk populations and within families is urgently needed. Implications for Practice: Nurse practitioners must remain informed of the epidemiology of common and emerging drug-resistant organisms in their patient populations. PMID:18271763

  19. Vitamin D sufficiency and Staphylococcus aureus infection in children.

    PubMed

    Wang, Jeffrey W; Hogan, Patrick G; Hunstad, David A; Fritz, Stephanie A

    2015-05-01

    Vitamin D promotes epithelial immunity by upregulating antimicrobial peptides, including LL-37, which have bactericidal activity against Staphylococcus aureus. We found that children with vitamin D deficiency or insufficiency [25-hydroxyvitamin D <30 ng/mL] were more likely to present with recurrent, rather than primary, S. aureus skin or soft tissue infection. Vitamin D sufficiency may be one of a myriad of host and environmental factors that can be directly impacted to reduce the frequency of S. aureus skin and soft tissue infection. PMID:25860535

  20. Staphylococcus aureus Infections in New Zealand, 2000–2011

    PubMed Central

    Zhang, Jane; Ritchie, Stephen R.; Roberts, Sally A.; Fraser, John D.; Baker, Michael G.

    2014-01-01

    The incidence rate for invasive and noninvasive Staphylococcus aureus infections in New Zealand is among the highest reported in the developed world. Using nationally collated hospital discharge data, we analyzed the epidemiology of serious S. aureus infections in New Zealand during 2000–2011. During this period, incidence of S. aureus skin and soft tissue infections increased significantly while incidence of staphylococcal sepsis and pneumonia remained stable. We observed marked ethnic and sociodemographic inequality across all S. aureus infections; incidence rates for all forms of S. aureus infections were highest among Māori and Pacific Peoples and among patients residing in areas of high socioeconomic deprivation. The increased incidence of S. aureus skin and soft tissue infections, coupled with the demographic disparities, is of considerable concern. Future work should aim to reduce this disturbing national trend. PMID:24960446

  1. Molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains isolated from outpatients with skin and soft tissue infections in Wuhan, China.

    PubMed

    Liu, Xiaoli; Liang, Jiansheng; Jiang, Yuanshan; Wang, Bin; Yuan, Hong; Zhang, Lihua; Zhou, Yanfei; Xu, Huiqiong; Zhou, Wang

    2016-06-01

    This study aims to investigate the antimicrobial susceptibility, molecular characteristics and virulence genes of community-acquired methicillin-resistant ITALIC! Staphylococcus aureus(CA-MRSA) isolates with skin and soft tissue infections (SSTIs). Outpatients with SSTIs visiting five medical and health institutions were enrolled from 2011 to 2013. Available ITALIC! S. aureus isolates were characterized by antimicrobial susceptibility testing, and detection of PVL genes. For CA-MRSA isolates, we performed typing of staphylococcal cassette chromosome ITALIC! mec(SCC ITALIC! mec), multi locus sequence typing (MLST) and carriage of 27 virulence genes. A total of 203 ITALIC! S. aureusstrains were isolated from 1400 outpatients with SSTIs, and 21 (10.3%) were CA-MRSA isolates. The positive rate of PVL genes among ITALIC! S. aureus, CA-MRSA and methicillin-susceptible ITALIC! S. aureus(MSSA) isolates were 39.4%, 71.4% and 35.7%, respectively. CA-MRSA strains had greater sensitivity to non-β-lactam antimicrobial agents. All CA-MRSA isolates belonged to SCC ITALIC! mecIV and V, accounting for 47.6% and 52.4%, respectively. ST59 was the most common lineage accounting for 76.2%; ST59-SCC ITALIC! mecIVa-PVL-positive clone was found to be the predominant clone, accounting for 38.1%. All CA-MRSA isolates were found to be positive for one or more virulence genes, 28.6% of isolates carried PVL, ITALIC! seb, ITALIC! sek, ITALIC! seq, ITALIC! hla, ITALIC! hlb, ITALIC! hldand ITALIC! hlg-2. CA-MRSA infections were relatively uncommon in outpatients with SSTIs, but they carried many virulence genes, ST59-SCC ITALIC! mecIV a-PVL-positive clone was the predominant clone in Wuhan, China. PMID:27060098

  2. Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 3: Current Perspectives on Skin and Soft Tissue Infections with Emphasis on Methicillin-resistant Staphylococcus aureus, Commonly Encountered Scenarios when Antibiotic Use May Not Be Needed, and Concluding Remarks on Rational Use of Antibiotics in Dermatology.

    PubMed

    Del Rosso, James Q; Rosen, Ted; Thiboutot, Diane; Webster, Guy F; Gallo, Richard L; Leyden, James J; Walker, Clay; Zhanel, George; Eichenfield, Lawrence

    2016-06-01

    In this third article of the three-part series, management of skin and soft tissue infections is reviewed with emphasis on new information on methicillin-resistant Staphylococcus aureus. Due to changes in the evolution of methicillin-resistant Staphylococcus aureus clones, previous distinctions between healthcare-acquired methicillin-resistant Staphylococcus aureus and community-acquired methicillin-resistant Staphylococcus aureus are currently much less clinically relevant. Many nosocomial cases of methicillin-resistant Staphylococcus aureus infection are now caused by community-acquired methicillin-resistant Staphylococcus aureus, with changing patterns of antibiotic susceptibility and resistance. Also reviewed are clinical scenarios where antibiotics may not be needed and suggestions for optimal use of antibiotic therapy for dermatologie conditions, including recommendations on perioperative antibiotic use. PMID:27386047

  3. 21 CFR 866.3700 - Staphylococcus aureus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Staphylococcus aureus serological reagents. 866... Staphylococcus aureus serological reagents. (a) Identification. Staphylococcus aureus serological reagents are... epidemiological information on these diseases. Certain strains of Staphylococcus aureus produce an...

  4. 21 CFR 866.3700 - Staphylococcus aureus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Staphylococcus aureus serological reagents. 866... Staphylococcus aureus serological reagents. (a) Identification. Staphylococcus aureus serological reagents are... epidemiological information on these diseases. Certain strains of Staphylococcus aureus produce an...

  5. 21 CFR 866.3700 - Staphylococcus aureus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Staphylococcus aureus serological reagents. 866... Staphylococcus aureus serological reagents. (a) Identification. Staphylococcus aureus serological reagents are... epidemiological information on these diseases. Certain strains of Staphylococcus aureus produce an...

  6. [Staphylococcus aureus and antibiotic resistance].

    PubMed

    Sancak, Banu

    2011-07-01

    After the report of first case of methicillin-resistant Staphylococcus aureus (MRSA) in 1961, MRSA become a major problem worldwide. Over the last decade MRSA strains have emerged as serious pathogens in nosocomial and community settings. Glycopeptides (vancomycin and teicoplanin) are still the current mainstay of therapy for infections caused by MRSA. In the last decade dramatic changes have occurred in the epidemiology of MRSA infections. The isolates with reduced susceptibility and in vitro resistance to vancomycin have emerged. Recently, therapeutic alternatives such as quinupristin/dalfopristin, linezolid, tigecycline and daptomycin have been introduced into clinical practice for treating MRSA infections. Nevertheless, these drugs are only approved for certain indication and resistance has already been reported. In this review, the new information on novel drugs for treating MRSA infections and the resistance mechanisms of these drugs were discussed. PMID:21935792

  7. Exploring Staphylococcus aureus pathways to disease for vaccine development

    PubMed Central

    DeDent, Andrea; Kim, Hwan Keun; Missiakas, Dominique; Schneewind, Olaf

    2012-01-01

    Staphylococcus aureus is a commensal of the human skin or nares and a pathogen that frequently causes skin and soft tissue infections as well as bacteremia and sepsis. Recent efforts in understanding the molecular mechanisms of pathogenesis revealed key virulence strategies of S. aureus in host tissues: bacterial scavenging of iron, induction of coagulation pathways to promote staphylococcal agglutination in the vasculature, and suppression of innate and adaptive immune responses. Advances in all three areas have been explored for opportunities in vaccine design in an effort to identify the critical protective antigens of S. aureus. Human clinical trials with specific subunit vaccines have failed, yet provide important insights for the design of future trials that must address the current epidemic of S. aureus infections with drug-resistant isolates (MRSA, methicillin-resistant S. aureus). PMID:22130613

  8. Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species.

    PubMed

    Ramsey, Matthew M; Freire, Marcelo O; Gabrilska, Rebecca A; Rumbaugh, Kendra P; Lemon, Katherine P

    2016-01-01

    Staphylococcus aureus-human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe-microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr) system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence toward a commensal state when exposed to commensal Corynebacterium species. PMID:27582729

  9. Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species

    PubMed Central

    Ramsey, Matthew M.; Freire, Marcelo O.; Gabrilska, Rebecca A.; Rumbaugh, Kendra P.; Lemon, Katherine P.

    2016-01-01

    Staphylococcus aureus–human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe–microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr) system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence toward a commensal state when exposed to commensal Corynebacterium species. PMID:27582729

  10. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  11. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  12. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  13. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  14. In vivo bioluminescence imaging to evaluate systemic and topical antibiotics against community-acquired methicillin-resistant Staphylococcus aureus-infected skin wounds in mice.

    PubMed

    Guo, Yi; Ramos, Romela Irene; Cho, John S; Donegan, Niles P; Cheung, Ambrose L; Miller, Lloyd S

    2013-02-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents. PMID:23208713

  15. Epidemiological data of staphylococcal scalded skin syndrome in France from 1997 to 2007 and microbiological characteristics of Staphylococcus aureus associated strains.

    PubMed

    Lamand, V; Dauwalder, O; Tristan, A; Casalegno, J S; Meugnier, H; Bes, M; Dumitrescu, O; Croze, M; Vandenesch, F; Etienne, J; Lina, G

    2012-12-01

    Epidemiological data on staphylococcal scalded skin syndromes (SSSS), including bullous impetigo (BI) and generalized exfoliative syndrome (GES), are scarce. To better characterize SSSS and associated Staphylococcus aureus strains, we conducted a retrospective study of 349 cases collected in France between 1997 and 2007 by the National Reference Centre of Staphylococci. Our results showed a stationary evolution of SSSS cases, with a heterogeneous distribution of cases in France. Although notification was not exhaustive, we estimated an incidence of 0.56 cases/year/million inhabitants, in accordance with previous studies conducted in France and Europe, with a median age of 2 years old and sex ratios of 1. A seasonal effect was observed, with a higher GES/BI ratio in autumn compared with other seasons, which could be explained by the impact of viral co-infection. Genetic analysis of S. aureus strains showed that accessory gene regulator (agr) 4, exfoliative toxin A (eta) and B (etb) genes, staphylococcal and enterotoxin-like O (selo) gene and agr4 etb selo profiles were predominantly associated with GES, whereas agr2 eta and agr4 eta selo were more frequently observed with BI. Only one methicillin-resistant strain was found. Protein A (spa) typing identified two main genotypes: spa clonal complex (CC) 159/sequence-type (ST) 121 (75%) and spaCC346/ST15 (18%). spaCC159 was mainly associated with agr4 eta etb selo, agr4 eta selo and agr4 etb selo, and spaCC346 was mainly associated with agr2 eta, suggesting that French SSSS cases are caused by these two main lineages. However, in a multivariate analysis, only etb was independently associated with GES. PMID:23078129

  16. Hidden Staphylococcus aureus Carriage: Overrated or Underappreciated?

    PubMed Central

    2016-01-01

    ABSTRACT Staphylococcus aureus is a persistent companion bacterial species in one-third of humankind. Reservoirs include the nasal and nasopharyngeal cavities, skin, and gastrointestinal (GI) tract. Despite earlier claims that colonization of individuals is caused by clonal organisms, next-generation sequencing (NGS) has revealed that resident type heterogeneity is not exceptional. Carriage, whether overt or hidden, is correlated with a risk of autoinfection. In a recent article in mBio, it was shown that, based on staphylococcal genome sequencing, low-level GI persistence may cause long-term nosocomial outbreaks [L. Senn et al., 7(1):e02039-15, 2016, doi:10.1128/mBio.02039-15]. Institutional endemicity with methicillin-resistant S. aureus (MRSA) sequence type 228 (ST228) is shown to originate not from high-level nasal carriage or poor compliance with infection control practice but from low-grade asymptomatic GI colonization. This shows the power of NGS in elucidating staphylococcal epidemiology and, even more important, demonstrates that (drug-resistant) microorganisms may possess stealthy means of persistence. Identifying these persistence mechanisms is key to successful infection control. PMID:26884429

  17. Use of the Antimicrobial Peptide Pardaxin (GE33) To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice with Skin Injuries

    PubMed Central

    Huang, Han-Ning; Pan, Chieh-Yu; Chan, Yi-Lin

    2014-01-01

    Antimicrobial peptides (AMPs) have recently been determined to be potential candidates for treating drug-resistant bacterial infections. Pardaxin (GE33), a marine antimicrobial peptide, has been reported to possess antimicrobial function. In this study, we investigated whether pardaxin promoted healing of contaminated wounds in mice. One square centimeter of outer skin was excised from the ventral region of mice, and a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA) was applied in the presence or absence of methicillin, vancomycin, or pardaxin. While untreated mice and mice treated with methicillin died within 3 days, mice treated with pardaxin survived infection. Pardaxin decreased MRSA bacterial counts in the wounded region and also enhanced wound closure. Reepithelialization and dermal maturation were also faster in mice treated with pardaxin than in mice treated with vancomycin. In addition, pardaxin treatment controlled excess recruitment of monocytes and macrophages and increased the expression of vascular endothelial growth factor (VEGF). In conclusion, these results suggest that pardaxin is capable of enhancing wound healing. Furthermore, this study provides an excellent platform for comparing the antimicrobial activities of peptide and nonpeptide antibiotics. PMID:24366739

  18. Risk factors for methicillin-resistant Staphylococcus aureus skin and soft tissue infection in MRSA-colonized patients discharged from a Veterans Affairs hospital.

    PubMed

    Cadena, J; Richardson, A M; Frei, C R

    2016-02-01

    Currently, limited studies have quantified the risk of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) for MRSA-colonized patients on discharge from hospital. Our retrospective, case-control study identified independent risk factors for the development of MRSA SSTIs among such patients detected by active MRSA nasal screening in an acute care hospital by PCR on admission, and bacteriological cultures on discharge. Cases were MRSA-colonized patients aged ⩾18 years who developed a MRSA SSTI post-discharge and controls were those who did not develop a MRSA SSTI post-discharge. Controls were matched to cases by length of follow-up (±10 days) for up to 18 months. Potential demographic and clinical risk factors for MRSA infection were identified using electronic queries and manual chart abstraction; data were compared by standard statistical tests and variables with P values ⩽0·05 in bivariable analysis were entered into a logistic regression model. Multivariable analysis demonstrated prior hospital admission within 12 months (P = 0·02), prior MRSA infection (P = 0·05), and previous myocardial infarction (P = 0·01) were independently predictive of a MRSA SSTI post-discharge. Identification of MRSA colonization upon admission and recognition of risk factors could help identify a high-risk population that could benefit from MRSA SSTI prevention strategies. PMID:26194247

  19. Facing Antibiotic Resistance: Staphylococcus aureus Phages as a Medical Tool

    PubMed Central

    Kaźmierczak, Zuzanna; Górski, Andrzej; Dąbrowska, Krystyna

    2014-01-01

    Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The introduction of antibiotics led to a general belief that the problem of bacterial infections would be solved. Nonetheless, pathogens including staphylococci have evolved mechanisms of drug resistance. Among current attempts to address this problem, phage therapy offers a promising alternative to combat staphylococcal infections. Here, we present an overview of current knowledge on staphylococcal infections and bacteriophages able to kill Staphylococcus, including experimental studies and available data on their clinical use. PMID:24988520

  20. Genetic Diversity of Staphylococcus aureus in Buruli Ulcer

    PubMed Central

    Amissah, Nana Ama; Glasner, Corinna; Ablordey, Anthony; Tetteh, Caitlin S.; Kotey, Nana Konama; Prah, Isaac; van der Werf, Tjip S.; Rossen, John W.; van Dijl, Jan Maarten; Stienstra, Ymkje

    2015-01-01

    Background Buruli ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans. Previous studies have shown that wounds of BU patients are colonized with M. ulcerans and several other microorganisms, including Staphylococcus aureus, which may interfere with wound healing. The present study was therefore aimed at investigating the diversity and topography of S. aureus colonizing BU patients during treatment. Methodology We investigated the presence, diversity, and spatio-temporal distribution of S. aureus in 30 confirmed BU patients from Ghana during treatment. S. aureus was isolated from nose and wound swabs, and by replica plating of wound dressings collected bi-weekly from patients. S. aureus isolates were characterized by multiple-locus variable number tandem repeat fingerprinting (MLVF) and spa-typing, and antibiotic susceptibility was tested. Principal Findings Nineteen (63%) of the 30 BU patients tested positive for S. aureus at least once during the sampling period, yielding 407 S. aureus isolates. Detailed analysis of 91 isolates grouped these isolates into 13 MLVF clusters and 13 spa-types. Five (26%) S. aureus-positive BU patients carried the same S. aureus genotype in their anterior nares and wounds. S. aureus isolates from the wounds of seven (37%) patients were distributed over two different MLVF clusters. Wounds of three (16%) patients were colonized with isolates belonging to two different genotypes at the same time, and five (26%) patients were colonized with different S. aureus types over time. Five (17%) of the 30 included BU patients tested positive for methicillin-resistant S. aureus (MRSA). Conclusion/Significance The present study showed that the wounds of many BU patients were contaminated with S. aureus, and that many BU patients from the different communities carried the same S. aureus genotype during treatment. This calls for improved wound care and hygiene. PMID:25658641

  1. The Human Nasal Microbiota and Staphylococcus aureus Carriage

    PubMed Central

    Frank, Daniel N.; Feazel, Leah M.; Bessesen, Mary T.; Price, Connie S.; Janoff, Edward N.; Pace, Norman R.

    2010-01-01

    Background Colonization of humans with Staphylococcus aureus is a critical prerequisite of subsequent clinical infection of the skin, blood, lung, heart and other deep tissues. S. aureus persistently or intermittently colonizes the nares of ∼50% of healthy adults, whereas ∼50% of the general population is rarely or never colonized by this pathogen. Because microbial consortia within the nasal cavity may be an important determinant of S. aureus colonization we determined the composition and dynamics of the nasal microbiota and correlated specific microorganisms with S. aureus colonization. Methodology/Principal Findings Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers). Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp.), with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp.) and Proteobacteria (e.g. Enterobacter spp). In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis (p = 0.004). Conclusions/Significance The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization. PMID:20498722

  2. Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion.

    PubMed

    Vecchio, Daniela; Dai, Tianhong; Huang, Liyi; Fantetti, Lia; Roncucci, Gabrio; Hamblin, Michael R

    2013-09-01

    Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). PMID:22987338

  3. Review on Panton Valentine leukocidin toxin carriage among Staphylococcus aureus.

    PubMed

    Shrestha, B

    2013-09-01

    Panton Valentine leukocidin is a toxin making pores in the polymorphonuclear cells which is a virulence factor of some strains of Staphylococcus aureus. Initially it was produced by methicillin susceptible Staphylococcus aureus only. Later with the acquisition of mecA gene has lead it to be PVL positive methicillin resistant Staphylococcus aureus. Since MRSA are resistant to many antibiotics and further they produce a toxin the infections by PVL positive MRSA has become a challenge. PVL positive MRSA a virulent strain of drug resistant superbug MRSA that has spread around the world, has claimed many lives in UK, Europe, USA and Australia. Some strains of superbug attack the healthy young people and kill within 24 hrs. PVL positive Staphylococcus aureus has been reported to be associated with skin and soft tissue infections however they also cause invasive infections and necrotizing pneumonia. These microorganisms known to be community associated have spread to hospitals. Hospital acquired infection by such microorganisms lead to an increase in mortality hence should be controlled before they become prevalent in hospitals. PMID:24908537

  4. The changing epidemiology of Staphylococcus aureus?

    PubMed Central

    Chambers, H. F.

    2001-01-01

    Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially. PMID:11294701

  5. Triclosan promotes Staphylococcus aureus nasal colonization.

    PubMed

    Syed, Adnan K; Ghosh, Sudeshna; Love, Nancy G; Boles, Blaise R

    2014-01-01

    The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health. PMID:24713325

  6. Neutrophil-Mediated Phagocytosis of Staphylococcus aureus

    PubMed Central

    van Kessel, Kok P. M.; Bestebroer, Jovanka; van Strijp, Jos A. G.

    2014-01-01

    Initial elimination of invading Staphylococcus aureus from the body is mediated by professional phagocytes. The neutrophil is the major phagocyte of the innate immunity and plays a key role in the host defense against staphylococcal infections. Opsonization of the bacteria with immunoglobulins and complement factors enables efficient recognition by the neutrophil that subsequently leads to intracellular compartmentalization and killing. Here, we provide a review of the key processes evolved in neutrophil-mediated phagocytosis of S. aureus and briefly describe killing. As S. aureus is not helpless against the professional phagocytes, we will also highlight its immune evasion arsenal related to phagocytosis. PMID:25309547

  7. The T Cell Response to Staphylococcus aureus

    PubMed Central

    Bröker, Barbara M.; Mrochen, Daniel; Péton, Vincent

    2016-01-01

    Staphylococcus aureus (S. aureus) is a dangerous pathogen and a leading cause of both nosocomial and community acquired bacterial infection worldwide. However, on the other hand, we are all exposed to this bacterium, often within the first hours of life, and usually manage to establish equilibrium and coexist with it. What does the adaptive immune system contribute toward lifelong control of S. aureus? Will it become possible to raise or enhance protective immune memory by vaccination? While in the past the S. aureus-specific antibody response has dominated this discussion, the research community is now coming to appreciate the role that the cellular arm of adaptive immunity, the T cells, plays. There are numerous T cell subsets, each with differing functions, which together have the ability to orchestrate the immune response to S. aureus and hence to tip the balance between protection and pathology. This review summarizes the state of the art in this dynamic field of research. PMID:26999219

  8. Selenium nanoparticles inhibit Staphylococcus aureus growth

    PubMed Central

    Tran, Phong A; Webster, Thomas J

    2011-01-01

    Staphylococcus aureus is a key bacterium commonly found in numerous infections. S. aureus infections are difficult to treat due to their biofilm formation and documented antibiotic resistance. While selenium has been used for a wide range of applications including anticancer applications, the effects of selenium nanoparticles on microorganisms remain largely unknown to date. The objective of this in vitro study was thus to examine the growth of S. aureus in the presence of selenium nanoparticles. Results of this study provided the first evidence of strongly inhibited growth of S. aureus in the presence of selenium nanoparticles after 3, 4, and 5 hours at 7.8, 15.5, and 31 μg/mL. The percentage of live bacteria also decreased in the presence of selenium nanoparticles. Therefore, this study suggests that selenium nanoparticles may be used to effectively prevent and treat S. aureus infections and thus should be further studied for such applications. PMID:21845045

  9. Weight-based antibiotic dosing in a real-world European study of complicated skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus.

    PubMed

    Lawson, W; Nathwani, D; Eckmann, C; Corman, S; Stephens, J; Solem, C; Macahilig, C; Li, J; Baillon-Plot, N; Charbonneau, C; Haider, S

    2015-09-01

    We aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs. PMID:26206621

  10. Hygiene Strategies to Prevent Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections: A Cluster-Randomized Controlled Trial Among High-Risk Military Trainees

    PubMed Central

    Ellis, Michael W.; Schlett, Carey D.; Millar, Eugene V.; Wilkins, Kenneth J.; Crawford, Katrina B.; Morrison-Rodriguez, Stephanie M.; Pacha, Laura A.; Gorwitz, Rachel J.; Lanier, Jeffrey B.; Tribble, David R.

    2014-01-01

    Background. Effective measures are needed to prevent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) in high-risk community settings. The study objective was to evaluate the effect of personal hygiene–based strategies on rates of overall SSTI and MRSA SSTI. Methods. We conducted a prospective, field-based, cluster-randomized trial in US Army Infantry trainees from May 2010 through January 2012. There were 3 study groups with incrementally increased education and hygiene-based interventions: standard (S), enhanced standard (ES), and chlorhexidine (CHG). The primary endpoints were incidence of overall SSTI and MRSA SSTI. Results. The study included 30 209 trainees constituting 540 platoons (168 S, 192 ES, and 180 CHG). A total of 1203 (4%) participants developed SSTI, 316 (26%) due to MRSA. The overall SSTI rate was 4.15 (95% confidence interval [CI], 3.77–4.58) per 100 person-cycles. SSTI rates by study group were 3.48 (95% CI, 2.87–4.22) for S, 4.18 (95% CI, 3.56–4.90) for ES, and 4.71 (95% CI, 4.03–5.50) for CHG. The MRSA SSTI rate per 100 person-cycles for all groups was 1.10 (95% CI, .91–1.32). MRSA SSTI rates by study group were 1.0 (95% CI, .70–1.42) for S, 1.29 (95% CI, .98–1.71) for ES, and 0.97 (95% CI, .70–1.36) for CHG. Conclusions. Personal hygiene and education measures, including once-weekly use of chlorhexidine body wash, did not prevent overall SSTI or MRSA SSTI in a high-risk population of military trainees. Clinical Trials Registration. NCT01105767. PMID:24633684

  11. Food compounds inhibit Staphylococcus aureus bacteria and the toxicity of Staphylococcus Enterotoxin A (SEA) associated with atopic dermatitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Atopic dermatitis or eczema is characterized by skin rashes and itching is an inflammatory disease that affects 10-20% of children and 1-3% of adults. Staphylococcus aureus bacteria are present on the skin of nearly all patients with atopic dermatitis. Antibiotics that suppress colonization of S. au...

  12. Methicillin-Resistant Staphylococcus aureus Adaptation to Human Keratinocytes

    PubMed Central

    Soong, Grace; Paulino, Franklin; Wachtel, Sarah; Parker, Dane; Wickersham, Matthew; Zhang, Dongni; Brown, Armand; Lauren, Christine; Dowd, Margaret; West, Emily; Horst, Basil; Planet, Paul

    2015-01-01

    ABSTRACT Skin is the most common site of Staphylococcus aureus infection. While most of these infections are self-limited, recurrent infections are common. Keratinocytes and recruited immune cells participate in skin defense against infection. We postulated that S. aureus is able to adapt to the milieu within human keratinocytes to avoid keratinocyte-mediated clearance. From a collection of S. aureus isolated from chronically infected patients with atopic dermatitis, we noted 22% had an agr mutant-like phenotype. Using several models of human skin infection, we demonstrate that toxin-deficient, agr mutants of methicillin-resistant S. aureus (MRSA) USA300 are able to persist within keratinocytes by stimulating autophagy and evading caspase-1 and inflammasome activation. MRSA infection induced keratinocyte autophagy, as evidenced by galectin-8 and LC3 accumulation. Autophagy promoted the degradation of inflammasome components and facilitated staphylococcal survival. The recovery of more than 58% agr or RNAIII mutants (P < 0.0001) of an inoculum of wild-type (WT) MRSA from within wortmannin-treated keratinocytes compared to control keratinocytes reflected the survival advantage for mutants no longer expressing agr-dependent toxins. Our results illustrate the dynamic interplay between S. aureus and keratinocytes that can result in the selection of mutants that have adapted specifically to evade keratinocyte-mediated clearance mechanisms. PMID:25900653

  13. The Heme Sensor System of Staphylococcus aureus

    PubMed Central

    Stauff, Devin L.; Skaar, Eric P.

    2016-01-01

    The important human pathogen Staphylococcus aureus is able to satisfy its nutrient iron requirement by acquiring heme from host hemoglobin in the context of infection. However, heme acquisition exposes S. aureus to heme toxicity. In order to detect the presence of toxic levels of exogenous heme, S. aureus is able to sense heme through the heme sensing system (HssRS) two-component system. Upon sensing heme, HssRS directly regulates the expression of the heme-regulated ABC transporter HrtAB, which alleviates heme toxicity. Importantly, the inability to sense or respond to heme alters the virulence of S. aureus, highlighting the importance of heme sensing and detoxification to staphylococcal pathogenesis. Furthermore, potential orthologues of the Hss and Hrt systems are found in many species of Gram-positive bacteria, a possible indication that heme stress is a challenge faced by bacteria whose habitats include host tissues rich in heme. PMID:19494582

  14. Generation of Ramoplanin-Resistant Staphylococcus aureus

    PubMed Central

    Schmidt, John W.; Greenough, Adrienne; Burns, Michelle; Luteran, Andrea E.; McCafferty, Dewey G.

    2013-01-01

    Ramoplanin is a lipoglycodepsipeptide antimicrobial active against clinically important Gram-positive bacteria including methicillin resistant Staphylococcus aureus. To proactively examine ramoplanin resistance, we subjected S. aureus NCTC 8325-4 to serial passage in the presence of increasing concentrations of ramoplanin, generating the markedly resistant strain RRSA16. Susceptibility testing of RRSA16 revealed the unanticipated acquisition of cross-resistance to vancomycin and nisin. RRSA16 displayed phenotypes, including a thickened cell wall and reduced susceptibility to Triton X-100 induced autolysis, which are associated with vancomycin intermediate resistant S. aureus strains. Passage of RRSA16 for 18 days in drug-free medium yielded strain R16-18d with restored antibiotic susceptibility. The RRSA16 isolate may be used to identify the genetic and biochemical basis for ramoplanin-resistance and further our understanding of the evolution of antibiotic cross-resistance mechanisms in S. aureus. PMID:20659164

  15. Generation of ramoplanin-resistant Staphylococcus aureus.

    PubMed

    Schmidt, John W; Greenough, Adrienne; Burns, Michelle; Luteran, Andrea E; McCafferty, Dewey G

    2010-09-01

    Ramoplanin is a lipoglycodepsipeptide antimicrobial active against clinically important Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. To proactively examine ramoplanin resistance, we subjected S. aureus NCTC 8325-4 to serial passage in the presence of increasing concentrations of ramoplanin, generating the markedly resistant strain RRSA16. Susceptibility testing of RRSA16 revealed the unanticipated acquisition of cross-resistance to vancomycin and nisin. RRSA16 displayed phenotypes, including a thickened cell wall and reduced susceptibility to Triton X-100-induced autolysis, which are associated with vancomycin intermediate-resistant S. aureus strains. Passage of RRSA16 for 18 days in a drug-free medium yielded strain R16-18d with restored antibiotic susceptibility. The RRSA16 isolate may be used to identify the genetic and biochemical basis for ramoplanin resistance and to further our understanding of the evolution of antibiotic cross-resistance mechanisms in S. aureus. PMID:20659164

  16. Physicochemical characterization of Staphylococcus aureus-lysing LysK enzyme in complexes with polycationic

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Staphylococcus aureus causes many serious visceral, skin, and respiratory diseases. About 90% of clinical strains are multi-drug resistant, but the use of bacteriophage lytic enzymes offers a viable alternative to antibiotic therapy. LysK, the phage K endolysin can lyse S. aureus when purified and ...

  17. Genomic Analysis of Companion Rabbit Staphylococcus aureus

    PubMed Central

    Holmes, Mark A.; Harrison, Ewan M.; Fisher, Elizabeth A.; Graham, Elizabeth M.; Parkhill, Julian; Foster, Geoffrey; Paterson, Gavin K.

    2016-01-01

    In addition to being an important human pathogen, Staphylococcus aureus is able to cause a variety of infections in numerous other host species. While the S. aureus strains causing infection in several of these hosts have been well characterised, this is not the case for companion rabbits (Oryctolagus cuniculus), where little data are available on S. aureus strains from this host. To address this deficiency we have performed antimicrobial susceptibility testing and genome sequencing on a collection of S. aureus isolates from companion rabbits. The findings show a diverse S. aureus population is able to cause infection in this host, and while antimicrobial resistance was uncommon, the isolates possess a range of known and putative virulence factors consistent with a diverse clinical presentation in companion rabbits including severe abscesses. We additionally show that companion rabbit isolates carry polymorphisms within dltB as described as underlying host-adaption of S. aureus to farmed rabbits. The availability of S. aureus genome sequences from companion rabbits provides an important aid to understanding the pathogenesis of disease in this host and in the clinical management and surveillance of these infections. PMID:26963381

  18. Genomic Analysis of Companion Rabbit Staphylococcus aureus.

    PubMed

    Holmes, Mark A; Harrison, Ewan M; Fisher, Elizabeth A; Graham, Elizabeth M; Parkhill, Julian; Foster, Geoffrey; Paterson, Gavin K

    2016-01-01

    In addition to being an important human pathogen, Staphylococcus aureus is able to cause a variety of infections in numerous other host species. While the S. aureus strains causing infection in several of these hosts have been well characterised, this is not the case for companion rabbits (Oryctolagus cuniculus), where little data are available on S. aureus strains from this host. To address this deficiency we have performed antimicrobial susceptibility testing and genome sequencing on a collection of S. aureus isolates from companion rabbits. The findings show a diverse S. aureus population is able to cause infection in this host, and while antimicrobial resistance was uncommon, the isolates possess a range of known and putative virulence factors consistent with a diverse clinical presentation in companion rabbits including severe abscesses. We additionally show that companion rabbit isolates carry polymorphisms within dltB as described as underlying host-adaption of S. aureus to farmed rabbits. The availability of S. aureus genome sequences from companion rabbits provides an important aid to understanding the pathogenesis of disease in this host and in the clinical management and surveillance of these infections. PMID:26963381

  19. Triclosan Promotes Staphylococcus aureus Nasal Colonization

    PubMed Central

    Syed, Adnan K.; Ghosh, Sudeshna; Love, Nancy G.; Boles, Blaise R.

    2014-01-01

    ABSTRACT The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. PMID:24713325

  20. Antibiotics, Acne, and Staphylococcus aureus Colonization

    PubMed Central

    Fanelli, Matthew; Kupperman, Eli; Lautenbach, Ebbing; Edelstein, Paul H.; Margolis, David J.

    2011-01-01

    Objectives To determine the frequency of Staphylococcus aureus colonization among patients with acne and to compare the susceptibility patterns between the patients who are using antibiotics and those who are not using antibiotics. Design Survey (cross-sectional) study of patients treated for acne. Setting Dermatology outpatient office practice Participants The study included 83 patients who were undergoing treatment and evaluation for acne. Main Outcome Measure Colonization of the nose or throat with S aureus. Results A total of 36 of the 83 participants (43%) were colonized with S aureus. Two of the 36 patients (6%) had methicillin-resistant S aureus; 20 (56%) had S aureus solely in their throat; 9 (25%) had S aureus solely in their nose; and 7 (19%) had S aureus in both their nose and their throat. When patients with acne who were antibiotic users were compared with nonusers, the prevalence odds ratio for the colonization of S aureus was 0.16 (95% confidence interval [CI], 0.08–1.37) after 1 to 2 months of exposure and increased to 0.52 (95% CI, 0.12–2.17) after 2 months of exposure (P =.31). Many of the S aureus isolates were resistant to treatment with clindamycin and erythromycin (40% and 44%, respectively), particularly the nasal isolates. Very few showed resistance rates (<10%) to treatment with tetracycline antibiotics. Conclusion Unlike current dogma about the long-term use of antimicrobial agents, the prolonged use of tetracycline antibiotics commonly used to treat acne lowered the prevalence of colonization by S aureus and did not increase resistance to the tetracycline antibiotics. PMID:21482860

  1. Epidemiology of Staphylococcus aureus during space flight

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.; Chidambaram, M.; Heath, J. D.; Mallary, L.; Mishra, S. K.; Sharma, B.; Weinstock, G. M.

    1996-01-01

    Staphylococcus aureus was isolated over 2 years from Space Shuttle mission crewmembers to determine dissemination and retention of bacteria. Samples before and after each mission were from nasal, throat, urine, and feces and from air and surface sampling of the Space Shuttle. DNA fingerprinting of samples by digestion of DNA with SmaI restriction endonuclease followed by pulsed-field gel electrophoresis showed S. aureus from each crewmember had a unique fingerprint and usually only one strain was carried by an individual. There was only one instance of transfer between crewmembers. Strains from interior surfaces after flight matched those of crewmembers, suggesting microbial fingerprinting may have forensic application.

  2. Antibiotic Combinations with Daptomycin for Treatment of Staphylococcus aureus Infections

    PubMed Central

    Nadrah, Kristina; Strle, Franc

    2011-01-01

    Daptomycin is a lipopeptide antibiotic with a unique mechanism of action on Gram-positive bacteria. It is approved for treatment of skin and soft-tissue infections with Gram-positive bacteria, bacteraemia and right-sided infective endocarditis caused by Staphylococcus aureus. Diminishing susceptibility of S. aureus to daptomycin during treatment of complicated infections and clinical failure have been described. Combinations of daptomycin with other antibiotics including gentamicin, rifampin, beta-lactams, trimethoprim/sulfamethoxazole (TMP-SMX), or clarithromycin present a new approach for therapy. In vitro and animal studies have shown that such combinations may, in some cases, be superior to daptomycin monotherapy. In this paper we focus on the antibiotic combinations for complicated S. aureus infections. PMID:22312555

  3. Anatomical patterns of colonization of pets with staphylococcal species in homes of people with methicillin-resistant Staphylococcus aureus (MRSA) skin or soft tissue infection (SSTI).

    PubMed

    Iverson, S A; Brazil, A M; Ferguson, J M; Nelson, K; Lautenbach, E; Rankin, S C; Morris, D O; Davis, M F

    2015-03-23

    Methicillin-resistant strains of Staphylococcus aureus (MRSA), Staphylococcus pseudintermedius (MRSP), and other pathogenic staphylococci can cause infections in companion animals and humans. Identification of colonized animals is fundamental to research and practice needs, but harmonized methods have not yet been established. To establish the optimal anatomic site for the recovery of methicillin-resistant coagulase positive staphylococci (CPS), survey data and swabs were collected from 196 pets (dogs, cats, reptiles, birds, fish and pocket pets) that lived in households with an MRSA-infected person. Using broth-enrichment culture and PCR for speciation, S. aureus was identified in 27 of 179 (15%) pets sampled at baseline and 19 of 125 (15%) pets sampled at a three-month follow-up home visit. S. pseudintermedius was isolated from 33 of 179 (18%) pets sampled at baseline and 21 of 125 (17%) of pets sampled at follow-up. The baseline MRSA and MRSP prevalence was 8% and 1% respectively from 145 mammalian pets. The follow-up MRSA and MRSP prevalence was 7% and <1% respectively from 95 mammalian pets. The mouth was the most sensitive single site sampled for isolation of S. aureus and S. pseudintermedius in mammals. In a subset of pets, from which all available isolates were identified, dual carriage of S. aureus and S. pseudintermedius was 22% at baseline and 11% at follow-up. These results identify the mouth as the most sensitive site to screen for pathogenic staphylococci and suggest that it should be included in sampling protocols. PMID:25623014

  4. Antimicrobial Peptide P60.4Ac-Containing Creams and Gel for Eradication of Methicillin-Resistant Staphylococcus aureus from Cultured Skin and Airway Epithelial Surfaces.

    PubMed

    Haisma, Elisabeth M; Göblyös, Anikó; Ravensbergen, Bep; Adriaans, Alwin E; Cordfunke, Robert A; Schrumpf, Jasmijn; Limpens, Ronald W A L; Schimmel, Kirsten J M; den Hartigh, Jan; Hiemstra, Pieter S; Drijfhout, Jan Wouter; El Ghalbzouri, Abdoelwaheb; Nibbering, Peter H

    2016-07-01

    We previously found the LL-37-derived peptide P60.4Ac to be effective against methicillin-resistant Staphylococcus aureus (MRSA) on human epidermal models (EMs). The goal of this study was to identify the preferred carrier for this peptide for topical application on skin and mucosal surfaces. We prepared P60.4Ac in three formulations, i.e., a water-in-oil cream with lanolin (Softisan 649), an oil-in-water cream with polyethylene glycol hexadecyl ether (Cetomacrogol), and a hydroxypropyl methylcellulose (hypromellose) 4000 gel. We tested the antimicrobial efficacy of the peptide in these formulations against mupirocin-resistant and -sensitive MRSA strains on EMs and bronchial epithelial models (BEMs). The cytotoxic effects of formulated P60.4Ac on these models were determined using histology and WST-1 and lactate dehydrogenase assays. Moreover, we assessed the stability of the peptide in these formulations with storage for up to 3 months. Killing of MRSA by P60.4Ac in the two creams was less effective than that by P60.4Ac in the hypromellose gel. In agreement with those findings, P60.4Ac in the hypromellose gel was highly effective in eradicating the two MRSA strains from EMs. We found that even 0.1% (wt/wt) P60.4Ac in the hypromellose gel killed >99% of the viable planktonic bacteria and >85% of the biofilm-associated bacteria on EMs. Hypromellose gels containing 0.1% and 0.5% (wt/wt) P60.4Ac effectively reduced the numbers of viable MRSA cells from BEMs by >90%. No cytotoxic effects of P60.4Ac in the hypromellose gel with up to 2% (wt/wt) P60.4Ac on keratinocytes in EMs and in the hypromellose gel with up to 0.5% (wt/wt) P60.4Ac on epithelial cells in BEMs were observed. High-performance liquid chromatography analysis showed that P60.4Ac was stable in the Softisan cream and the hypromellose gel but not in the Cetomacrogol cream. We conclude that P60.4Ac formulated in hypromellose gel is both stable and highly effective in eradicating MRSA from colonized EMs and

  5. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

    PubMed Central

    Davis, Joshua S.; Eichenberger, Emily; Holland, Thomas L.

    2015-01-01

    SUMMARY Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions. PMID:26016486

  6. Stability of Penicillinase Plasmids in Staphylococcus aureus

    PubMed Central

    Johnston, L. H.; Dyke, K. G. H.

    1971-01-01

    The isolation of mutants of Staphylococcus aureus that are affected in the stability of penicillinase plasmids is described. One mutation is plasmid borne and results in nonreplication of the plasmid at 42 C. A second type of mutation is host-borne and gives rise to instability of both mcrI and mcrII penicillinase plasmids but not a tetracycline-resistant plasmid. Images PMID:4105036

  7. [Ecthyma gangrenosum caused by Staphylococcus aureus].

    PubMed

    Jaque, Alejandra; Moll-Manzur, Catherina; Dossi, María Teresa; Berroeta-Mauriziano, Daniela; Araos-Baeriswyl, Esteban; Monsalve, Ximena

    2016-06-01

    Ecthyma gangrenosum is an uncommon necrotizing vasculitis, in most cases secondary to sepsis by Pseudo-mona aeruginosa in immunocompromised patients. However, there have been several reports of ecthyma gangre-nosum caused by other infectious etiologies. We report an unusual case of ecthyma gangrenosum associated with methicillin-resistant Staphylococcus aureus infection in a patient without the classic immunological risk factors described in the literature. PMID:27598286

  8. Staphylococcus aureus and Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in and Around Therapeutic Whirlpools in College Athletic Training Rooms

    PubMed Central

    Kahanov, Leamor; Kim, Young Kyun; Eberman, Lindsey; Dannelly, Kathleen; Kaur, Haninder; Ramalinga, A.

    2015-01-01

    Context: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a leading cause of skin and soft tissue infection in the nonhospitalized community. Care of the athletes in athletic training rooms is specifically designed with equipment tailored to the health care needs of the athletes, yet recent studies indicate that CA-MRSA is still prevalent in athletic facilities and that cleaning methods may not be optimal. Objective: To investigate the prevalence of Staphylococcus aureus and CA-MRSA in and around whirlpools in the athletic training room. Design: Cross-sectional study. Setting: National Collegiate Athletic Association Division I university. Patients or Other Participants: Student-athletes (n = 109) consisting of 46 men (42%) and 63 women (58%) representing 6 sports. Main Outcome Measure(s): Presence of MRSA and Staphylococcus aureus in and around the whirlpool structures relative to sport and number of athletes using the whirlpools. Results: We identified Staphylococcus aureus in 22% (n = 52/240) of the samples and MRSA in 0.8% (n = 2/240). A statistically significant difference existed between the number of athletes using the whirlpool and the presence of Staphylococcus aureus in and around the whirlpools (F2,238 = 2.445, P = .007). However, Staphylococcus aureus was identified regardless of whether multiple athletes used a whirlpool or no athletes used a whirlpool. We did not identify a relationship between the number of athletes who used a whirlpool and Staphylococcus aureus or MRSA density (P = .134). Conclusions: Staphylococcus aureus and MRSA were identified in and around the whirlpools. Transmission of the bacteria can be reduced by following the cleaning and disinfecting protocols recommended by the Centers for Disease Control and Prevention. Athletic trainers should use disinfectants registered by the Environmental Protection Agency to sanitize all whirlpools between uses. PMID:25710853

  9. Nonprofessional Phagocytic Cell Receptors Involved in Staphylococcus aureus Internalization

    PubMed Central

    Alva-Murillo, Nayeli; López-Meza, Joel Edmundo

    2014-01-01

    Staphylococcus aureus is a successful human and animal pathogen. The majority of infections caused by this pathogen are life threatening, primarily because S. aureus has developed multiple evasion strategies, possesses intracellular persistence for long periods, and targets the skin and soft tissues. Therefore, it is very important to understand the mechanisms employed by S. aureus to colonize and proliferate in these cells. The aim of this review is to describe the recent discoveries concerning the host receptors of nonprofessional phagocytes involved in S. aureus internalization. Most of the knowledge related to the interaction of S. aureus with its host cells has been described in professional phagocytic cells such as macrophages. Here, we showed that in nonprofessional phagocytes the α5β1 integrin host receptor, chaperons, and the scavenger receptor CD36 are the main receptors employed during S. aureus internalization. The characterization and identification of new bacterial effectors and the host cell receptors involved will undoubtedly lead to new discoveries with beneficial purposes. PMID:24826382

  10. Measurement and Impact of Staphylococcus aureus Colonization Pressure in Households

    PubMed Central

    Rodriguez, Marcela; Hogan, Patrick G.; Krauss, Melissa; Warren, David K.; Fritz, Stephanie A.

    2013-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) “colonization pressure” (CP) predicts infections in hospitals. We applied the CP concept to staphylococcal transmission within households. We tested the hypothesis that children with S aureus skin and soft tissue infection (SSTI) plus colonization (“cases”) with higher baseline household CP (HHCP) would be at greater risk for persistent colonization and recurrent SSTI during study period. Methods We collected baseline colonization swabs from 92 cases and 296 of their household contacts. Cases underwent decolonization. S aureus HHCP was calculated as the proportion of colonized household contacts at baseline (excluding cases). S aureus colonization and recurrent SSTI in cases were followed for 12 months. Results Overall, median S aureus HHCP was 60% (mean = 55%). For cases colonized with MRSA, median MRSA HHCP was 11% (mean 29%); methicillin-susceptible S aureus (MSSA)–colonized cases had a median MSSA HHCP of 50% (mean = 49%). Over 1 year, MRSA HHCP was an independent risk factor for persistent MRSA colonization in cases (each 10-unit increase in HHCP associated with an adjusted odds ratio of 1.25; 95% confidence interval, 1.06–1.47). HHCP was not associated with recurrent SSTI in cases. Conclusions MRSA HHCP is associated with persistent colonization in outpatients. Further studies are needed to determine the relationship between persistent colonization of household contacts, environmental contamination, and SSTI. PMID:23717786

  11. Agglutination of Staphylococcus aureus by Rabbit Sera

    PubMed Central

    Forsgren, Arne; Forsum, Urban

    1972-01-01

    Of 137 Staphylococcus aureus strains, 87 agglutinated in normal rabbit serum. The agglutination was shown to be caused by the Fc-part of immunoglobulin G (IgG). F(ab1)2-fragments of IgG and immunoglobulin M (IgM) in corresponding concentrations were unreactive. The agglutinating strains had a high or moderate content of protein A. Strains with a low content of protein A and protein A-negative mutants did not agglutinate. The importance of the reaction between the Fc part of IgG and protein A for serotyping of S. aureus is demonstrated. Two alternative methods for serotyping S. aureus are suggested, using either F(ab1)2 fragments of IgG or intact IgM. Images PMID:4564678

  12. Low level laser therapy (AlGaInP) applied at 5J/cm2 reduces the proliferation of Staphylococcus aureus MRSA in infected wounds and intact skin of rats*

    PubMed Central

    Silva, Daniela Conceição Gomes Gonçalves e; Plapler, Helio; da Costa, Mateus Matiuzzi; Silva, Silvio Romero Gonçalves e; de Sá, Maria da Conceição Aquino; Silva, Benedito Sávio Lima e

    2013-01-01

    BACKGROUND Laser therapy is a low cost, non-invasive procedure with good healing results. Doubts exist as to whether laser therapy action on microorganisms can justify research aimed at investigating its possible effects on bacteria-infected wounds. OBJECTIVE To assess the effect of low intensity laser on the rate of bacterial contamination in infected wounds in the skin of rats. METHODS An experimental study using 56 male Wistar rats. The animals were randomly divided into eight groups of seven each. Those in the "infected" groups were infected by Staphylococcus aureus MRSA in the dorsal region. Red laser diode (AlGaInP) 658nm, 5J/cm2 was used to treat the animals in the "treated" groups in scan for 3 consecutive days. Samples were drawn before inoculating bacteria and following laser treatment. For statistical analysis we used the nonparametric Wilcoxon (paired data) method with a significance level of p <0.05. RESULTS The statistical analysis of median values showed that the groups submitted to laser treatment had low bacterial proliferation. CONCLUSION The laser (AlGaInP), with a dose of 5J/cm2 in both intact skin and in wounds of rats infected with Staphylococcus aureus MRSA, is shown to reduce bacterial proliferation. PMID:23539003

  13. Modulation of Staphylococcus aureus spreading by water.

    PubMed

    Lin, Mei-Hui; Ke, Wan-Ju; Liu, Chao-Chin; Yang, Meng-Wei

    2016-01-01

    Staphylococcus aureus is known to spread rapidly and form giant colonies on the surface of soft agar and animal tissues by a process called colony spreading. So far, the mechanisms underlying spreading remain poorly understood. This study investigated the spreading phenomenon by culturing S. aureus and its mutant derivatives on Tryptic Soy Agarose (TSA) medium. We found that S. aureus extracts water from the medium and floats on water at 2.5 h after inoculation, which could be observed using phase contrast microscopy. The floating of the bacteria on water could be verified by confocal microscopy using an S. aureus strain that constitutively expresses green fluorescence protein. This study also found that as the density of bacterial colony increases, a quorum sensing response is triggered, resulting in the synthesis of the biosurfactants, phenolic-soluble modulins (PSMs), which weakens water surface tension, causing water to flood the medium surface to allow the bacteria to spread rapidly. This study reveals a mechanism that explains how an organism lacking a flagellar motor is capable of spreading rapidly on a medium surface, which is important to the understanding of how S. aureus spreads in human tissues to cause infections. PMID:27125382

  14. Modulation of Staphylococcus aureus spreading by water

    PubMed Central

    Lin, Mei-Hui; Ke, Wan-Ju; Liu, Chao-Chin; Yang, Meng-Wei

    2016-01-01

    Staphylococcus aureus is known to spread rapidly and form giant colonies on the surface of soft agar and animal tissues by a process called colony spreading. So far, the mechanisms underlying spreading remain poorly understood. This study investigated the spreading phenomenon by culturing S. aureus and its mutant derivatives on Tryptic Soy Agarose (TSA) medium. We found that S. aureus extracts water from the medium and floats on water at 2.5 h after inoculation, which could be observed using phase contrast microscopy. The floating of the bacteria on water could be verified by confocal microscopy using an S. aureus strain that constitutively expresses green fluorescence protein. This study also found that as the density of bacterial colony increases, a quorum sensing response is triggered, resulting in the synthesis of the biosurfactants, phenolic-soluble modulins (PSMs), which weakens water surface tension, causing water to flood the medium surface to allow the bacteria to spread rapidly. This study reveals a mechanism that explains how an organism lacking a flagellar motor is capable of spreading rapidly on a medium surface, which is important to the understanding of how S. aureus spreads in human tissues to cause infections. PMID:27125382

  15. Ecological Overlap and Horizontal Gene Transfer in Staphylococcus aureus and Staphylococcus epidermidis

    PubMed Central

    Méric, Guillaume; Miragaia, Maria; de Been, Mark; Yahara, Koji; Pascoe, Ben; Mageiros, Leonardos; Mikhail, Jane; Harris, Llinos G.; Wilkinson, Thomas S.; Rolo, Joana; Lamble, Sarah; Bray, James E.; Jolley, Keith A.; Hanage, William P.; Bowden, Rory; Maiden, Martin C.J.; Mack, Dietrich; de Lencastre, Hermínia; Feil, Edward J.; Corander, Jukka; Sheppard, Samuel K.

    2015-01-01

    The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of nine gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, there was considerable interspecies admixture of mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species. PMID:25888688

  16. Potassium Uptake Modulates Staphylococcus aureus Metabolism.

    PubMed

    Gries, Casey M; Sadykov, Marat R; Bulock, Logan L; Chaudhari, Sujata S; Thomas, Vinai C; Bose, Jeffrey L; Bayles, Kenneth W

    2016-01-01

    As a leading cause of community-associated and nosocomial infections, Staphylococcus aureus requires sophisticated mechanisms that function to maintain cellular homeostasis in response to its exposure to changing environmental conditions. The adaptation to stress and maintenance of homeostasis depend largely on membrane activity, including supporting electrochemical gradients and synthesis of ATP. This is largely achieved through potassium (K(+)) transport, which plays an essential role in maintaining chemiosmotic homeostasis, affects antimicrobial resistance, and contributes to fitness in vivo. Here, we report that S. aureus Ktr-mediated K(+) uptake is necessary for maintaining cytoplasmic pH and the establishment of a proton motive force. Metabolite analyses revealed that K(+) deficiency affects both metabolic and energy states of S. aureus by impairing oxidative phosphorylation and directing carbon flux toward substrate-level phosphorylation. Taken together, these results underline the importance of K(+) uptake in maintaining essential components of S. aureus metabolism. IMPORTANCE Previous studies describing mechanisms for K(+) uptake in S. aureus revealed that the Ktr-mediated K(+) transport system was required for normal growth under alkaline conditions but not under neutral or acidic conditions. This work focuses on the effect of K(+) uptake on S. aureus metabolism, including intracellular pH and carbon flux, and is the first to utilize a pH-dependent green fluorescent protein (GFP) to measure S. aureus cytoplasmic pH. These studies highlight the role of K(+) uptake in supporting proton efflux under alkaline conditions and uncover a critical role for K(+) uptake in establishing efficient carbon utilization. PMID:27340697

  17. Potassium Uptake Modulates Staphylococcus aureus Metabolism

    PubMed Central

    Gries, Casey M.; Sadykov, Marat R.; Bulock, Logan L.; Chaudhari, Sujata S.; Thomas, Vinai C.; Bose, Jeffrey L.

    2016-01-01

    ABSTRACT As a leading cause of community-associated and nosocomial infections, Staphylococcus aureus requires sophisticated mechanisms that function to maintain cellular homeostasis in response to its exposure to changing environmental conditions. The adaptation to stress and maintenance of homeostasis depend largely on membrane activity, including supporting electrochemical gradients and synthesis of ATP. This is largely achieved through potassium (K+) transport, which plays an essential role in maintaining chemiosmotic homeostasis, affects antimicrobial resistance, and contributes to fitness in vivo. Here, we report that S. aureus Ktr-mediated K+ uptake is necessary for maintaining cytoplasmic pH and the establishment of a proton motive force. Metabolite analyses revealed that K+ deficiency affects both metabolic and energy states of S. aureus by impairing oxidative phosphorylation and directing carbon flux toward substrate-level phosphorylation. Taken together, these results underline the importance of K+ uptake in maintaining essential components of S. aureus metabolism. IMPORTANCE Previous studies describing mechanisms for K+ uptake in S. aureus revealed that the Ktr-mediated K+ transport system was required for normal growth under alkaline conditions but not under neutral or acidic conditions. This work focuses on the effect of K+ uptake on S. aureus metabolism, including intracellular pH and carbon flux, and is the first to utilize a pH-dependent green fluorescent protein (GFP) to measure S. aureus cytoplasmic pH. These studies highlight the role of K+ uptake in supporting proton efflux under alkaline conditions and uncover a critical role for K+ uptake in establishing efficient carbon utilization. PMID:27340697

  18. Ultrastructural Study on the Antibacterial Activity of Artonin E versus Streptomycin against Staphylococcus aureus Strains

    PubMed Central

    Zajmi, Asdren; Mohd Hashim, Najihah; Noordin, Mohamed Ibrahim; Khalifa, Shaden A. M.; Ramli, Faiqah; Mohd Ali, Hapipah; El-Seedi, Hesham R.

    2015-01-01

    Staphylococci are facultative anaerobes, perfectly spherical un-encapsulated cocci, with a diameter not exceeding 1 micrometer in diameter. Staphylococcus aureus are generally harmless and remain confined to the skin unless they burrow deep into the body, causing life-threatening infections in bones, joints, bloodstream, heart valves and lungs. Among the 20 medically important staphylococci species, Staphylococcus aureus is one of the emerging human pathogens. Streptomycin had its highest potency against Staphylococcus infections despite the likelihood of getting a resistant type of staphylococcus strains. Methicillin-resistant S. aureus (MRSA) is the persister type of Staphylococcus aureus and was evolved after decades of antibiotic misuse. Inadequate penetration of the antibiotic is one of the principal factors related to success/failure of the therapy. The active drug needs to reach the bacteria at concentrations necessary to kill or suppress the pathogen's growth. In turn the effectiveness of the treatment relied on the physical properties of Staphylococcus aureus. Thus understanding the cell integrity, shape and roughness is crucial to the overall influence of the therapeutic agent on S. aureus of different origins. Hence our experiments were designed to clarify ultrastructural changes of S. aureus treated with streptomycin (synthetic compound) in comparison to artonin E (natural compound). In addition to the standard in vitro microbial techniques, we used transmission electron microscopy to study the disrupted cell architecture under antibacterial regimen and we correlate this with scanning electron microscopy (SEM) to compare results of both techniques. PMID:26030925

  19. SATRAT: Staphylococcus aureus transcript regulatory network analysis tool

    PubMed Central

    Nagarajan, Vijayaraj; Elasri, Mohamed O.

    2015-01-01

    Staphylococcus aureus is a commensal organism that primarily colonizes the nose of healthy individuals. S. aureus causes a spectrum of infections that range from skin and soft-tissue infections to fatal invasive diseases. S. aureus uses a large number of virulence factors that are regulated in a coordinated fashion. The complex regulatory mechanisms have been investigated in numerous high-throughput experiments. Access to this data is critical to studying this pathogen. Previously, we developed a compilation of microarray experimental data to enable researchers to search, browse, compare, and contrast transcript profiles. We have substantially updated this database and have built a novel exploratory tool—SATRAT—the S. aureus transcript regulatory network analysis tool, based on the updated database. This tool is capable of performing deep searches using a query and generating an interactive regulatory network based on associations among the regulators of any query gene. We believe this integrated regulatory network analysis tool would help researchers explore the missing links and identify novel pathways that regulate virulence in S. aureus. Also, the data model and the network generation code used to build this resource is open sourced, enabling researchers to build similar resources for other bacterial systems. PMID:25653902

  20. Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection.

    PubMed

    Ibberson, Carolyn B; Parlet, Corey P; Kwiecinski, Jakub; Crosby, Heidi A; Meyerholz, David K; Horswill, Alexander R

    2016-06-01

    Staphylococcus aureus is a leading cause of chronic biofilm infections. Hyaluronic acid (HA) is a large glycosaminoglycan abundant in mammalian tissues that has been shown to enhance biofilm formation in multiple Gram-positive pathogens. We observed that HA accumulated in an S. aureus biofilm infection using a murine implant-associated infection model and that HA levels increased in a mutant strain lacking hyaluronidase (HysA). S. aureus secretes HysA in order to cleave HA during infection. Through in vitro biofilm studies with HA, the hysA mutant was found to accumulate increased biofilm biomass compared to the wild type, and confocal microscopy showed that HA is incorporated into the biofilm matrix. Exogenous addition of purified HysA enzyme dispersed HA-containing biofilms, while catalytically inactive enzyme had no impact. Additionally, induction of hysA expression prevented biofilm formation and also dispersed an established biofilm in the presence of HA. These observations were corroborated in the implant model, where there was decreased dissemination from an hysA mutant biofilm infection compared to the S. aureus wild type. Histopathology demonstrated that infection with an hysA mutant caused significantly reduced distribution of tissue inflammation compared to wild-type infection. To extend these studies, the impact of HA and S. aureus HysA on biofilm-like aggregates found in joint infections was examined. We found that HA contributes to the formation of synovial fluid aggregates, and HysA can disrupt aggregate formation. Taken together, these studies demonstrate that HA is a relevant component of the S. aureus biofilm matrix and HysA is important for dissemination from a biofilm infection. PMID:27068096

  1. Emerging Functions for the Staphylococcus aureus RNome

    PubMed Central

    Felden, Brice

    2013-01-01

    Staphylococcus aureus is a leading pathogen for animals and humans, not only being one of the most frequently isolated bacteria in hospital-associated infections but also causing diseases in the community. To coordinate the expression of its numerous virulence genes for growth and survival, S. aureus uses various signalling pathways that include two-component regulatory systems, transcription factors, and also around 250 regulatory RNAs. Biological roles have only been determined for a handful of these sRNAs, including cis, trans, and cis-trans acting RNAs, some internally encoding small, functional peptides and others possessing dual or multiple functions. Here we put forward an inventory of these fascinating sRNAs; the proteins involved in their activities; and those involved in stress response, metabolisms, and virulence. PMID:24348246

  2. Methicillin-resistant Staphylococcus aureus: the superbug.

    PubMed

    Ippolito, Giuseppe; Leone, Sebastiano; Lauria, Francesco N; Nicastri, Emanuele; Wenzel, Richard P

    2010-10-01

    Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens in the nosocomial and community setting. Hospitalization costs associated with MRSA infections are substantially greater than those associated with methicillin-sensitive S. aureus (MSSA) infections, and MRSA has wider economic effects that involve indirect costs to the patient and to society. In addition, there is some evidence suggesting that MRSA infections increase morbidity and the risk of mortality. Glycopeptides are the backbone antibiotics for the treatment of MRSA infections. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Several new antimicrobials demonstrate in vitro activity against MRSA and other Gram-positive bacteria. Data from large surveys indicate that linezolid, daptomycin, and tigecycline are almost universally active against MRSA. This review will briefly discuss the epidemiology, costs, outcome, and therapeutic options for the management of MRSA infections. PMID:20851011

  3. A humanized monoclonal antibody targeting Staphylococcus aureus.

    PubMed

    Patti, Joseph M

    2004-12-01

    This current presentation describes the in vitro and in vivo characterization of Aurexis (tefibazumab), a humanized monoclonal antibody that exhibits a high affinity and specificity and for the Staphylococcus aureus MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) protein ClfA. Aurexis inhibited ClfA binding to human fibrinogen, and enhanced the opsonophagocytic uptake of ClfA-coated beads. Preclinical in vivo testing revealed that a single administration of Aurexis significantly protected against an IV challenge with a methicillin resistant S. aureus (MRSA) strain in murine septicemia and rabbit infective endocarditis (IE) models. Safety and pharmacokinetic data from a 19-patient phase I study support continued evaluation of Aurexis in phase II studies. PMID:15576200

  4. Antimicrobial therapy of Staphylococcus aureus bloodstream infection.

    PubMed

    Tacconelli, Evelina; Cataldo, Maria A

    2007-10-01

    Staphylococcus aureus bloodstream infection (BSI) contributes significantly to the morbidity and mortality of in-patients. The optimal therapy for methicillin-susceptible S. aureus BSI consists of penicillins. The efficacy of these drugs is well documented from several published data and supported from a long clinical experience. Methicillin-resistant S. aureus (MRSA) strains are responsible for the majority of nosocomial BSI and are recovered with increasing frequency at hospital admission. Although glycopeptides still represent the drugs of choice, there are several concerns on the treatment of MRSA BSI: reports of clinical failure with vancomycin treatment, regardless of the in vitro susceptibility; increasing reports of MRSA strains with reduced vancomycin susceptibility; difficulty in therapeutic dosage monitoring of teicoplanin; lack of evidence on the efficacy of combination therapy. Recently, new drugs have been introduced in the therapeutic arsenal for MRSA infections, but their clinical use is not yet clearly established for BSI. The review summarises evidence on present therapeutic options for the treatment of S. aureus BSI. PMID:17931086

  5. Pasteurella multocida pneumonia complicated by Staphylococcus aureus.

    PubMed

    Martyn, V; Swift, D

    1984-02-01

    A 71-year-old woman presented with acute non-cardiogenic pulmonary oedema. She proved to have a Pasteurella multocida pneumonia, with blood stream invasion by the organism, and required positive pressure ventilation for 53 days. Penicillin G., the drug of choice for this infection, failed to reverse the steady decline in her arterial oxygen-tension, and it was only after treatment with chloramphenicol and prednisolone that she began to improve. Serological tests strongly indicated the presence of a Staphylococcus aureus infection and the delay in giving antibiotics appropriate to this second pathogen may have been the reason for the patient's initial downhill course. PMID:6709548

  6. Staphylococcus aureus and Staphylococcus epidermidis Virulence Strains as Causative Agents of Persistent Infections in Breast Implants

    PubMed Central

    Chessa, Daniela; Ganau, Giulia; Spiga, Luisella; Bulla, Antonio; Mazzarello, Vittorio; Campus, Gian Vittorio; Rubino, Salvatore

    2016-01-01

    Staphylococcus epidermidis and Staphylococcus aureus are currently considered two of the most important pathogens in nosocomial infections associated with catheters and other medical implants and are also the main contaminants of medical instruments. However because these species of Staphylococcus are part of the normal bacterial flora of human skin and mucosal surfaces, it is difficult to discern when a microbial isolate is the cause of infection or is detected on samples as a consequence of contamination. Rapid identification of invasive strains of Staphylococcus infections is crucial for correctly diagnosing and treating infections. The aim of the present study was to identify specific genes to distinguish between invasive and contaminating S. epidermidis and S. aureus strains isolated on medical devices; the majority of our samples were collected from breast prostheses. As a first step, we compared the adhesion ability of these samples with their efficacy in forming biofilms; second, we explored whether it is possible to determine if isolated pathogens were more virulent compared with international controls. In addition, this work may provide additional information on these pathogens, which are traditionally considered harmful bacteria in humans, and may increase our knowledge of virulence factors for these types of infections. PMID:26811915

  7. Staphopains Modulate Staphylococcus aureus Biofilm Integrity

    PubMed Central

    Mootz, Joe M.; Malone, Cheryl L.; Shaw, Lindsey N.

    2013-01-01

    Staphylococcus aureus is a known cause of chronic biofilm infections that can reside on medical implants or host tissue. Recent studies have demonstrated an important role for proteinaceous material in the biofilm structure. The S. aureus genome encodes many secreted proteases, and there is growing evidence that these enzymes have self-cleavage properties that alter biofilm integrity. However, the specific contribution of each protease and mechanism of biofilm modulation is not clear. To address this issue, we utilized a sigma factor B (ΔsigB) mutant where protease activity results in a biofilm-negative phenotype, thereby creating a condition where the protease(s) responsible for the phenotype could be identified. Using a plasma-coated microtiter assay, biofilm formation was restored to the ΔsigB mutant through the addition of the cysteine protease inhibitor E-64 or by using Staphostatin inhibitors that specifically target the extracellular cysteine proteases SspB and ScpA (called Staphopains). Through construction of gene deletion mutants, we determined that an sspB scpA double mutant restored ΔsigB biofilm formation, and this recovery could be replicated in plasma-coated flow cell biofilms. Staphopain levels were also found to be decreased under biofilm-forming conditions, possibly allowing biofilm establishment. The treatment of S. aureus biofilms with purified SspB or ScpA enzyme inhibited their formation, and ScpA was also able to disperse an established biofilm. The antibiofilm properties of ScpA were conserved across S. aureus strain lineages. These findings suggest an underappreciated role of the SspB and ScpA cysteine proteases in modulating S. aureus biofilm architecture. PMID:23798534

  8. Survival of Staphylococcus aureus on fomites.

    PubMed

    Cuesta, Alicia; Nastri, Natalia; Bernat, Maria; Brusca, Maria; Turcot, Liliana; Nastri, Maria; Rosa, Alcira C

    2008-01-01

    The aim of this study was to evaluate duration of survival of Staphylococcus aureus on contaminated standardized fomites, such as sterilization paper (SP) and polyester previously sterilized in a steam autoclave, and to determine the potential inhibitory effects of the substrates (fabrics used to manufacture garments and special wrapping paper used in the dental setting) using the bacteriostasis test. The test was performed on two types of sterile standardized samples (T1 and T2). Sterility of the samples was validated following the protocol in use at the Department of Microbiology, after which the samples were inoculated with 50 microl of a calibrated suspension of Staphylococcus aureus (reference strain ATCC 25923) in the exponential growth phase, in a final concentration of 10(7) cfu/ml and 10(6) cfu/ml). The samples were incubated at 27 degrees C and survival and concentration of microorganisms attached to the surface of the substrates was determined at the following experimental time points: immediately post-contamination, and 3 hours, 24 hours, 3 days, and 7 days post-contamination. Recovery was determined and expressed as a percentage; the bacteriostasis test was performed and showed negative results. Our results suggest that the quantity of recovered microorganisms varies according to the type of substrate and that there is a relation between survival and incubation time of the inoculated substrate serving as an artificial niche. PMID:19177850

  9. Methicillin-Susceptible, Vancomycin-Resistant Staphylococcus aureus, Brazil.

    PubMed

    Panesso, Diana; Planet, Paul J; Diaz, Lorena; Hugonnet, Jean-Emmanuel; Tran, Truc T; Narechania, Apurva; Munita, Jose M; Rincon, Sandra; Carvajal, Lina P; Reyes, Jinnethe; Londoño, Alejandra; Smith, Hannah; Sebra, Robert; Deikus, Gintaras; Weinstock, George M; Murray, Barbara E; Rossi, Flavia; Arthur, Michel; Arias, Cesar A

    2015-10-01

    We report characterization of a methicillin-susceptible, vancomycin-resistant bloodstream isolate of Staphylococcus aureus recovered from a patient in Brazil. Emergence of vancomycin resistance in methicillin-susceptible S. aureus would indicate that this resistance trait might be poised to disseminate more rapidly among S. aureus and represents a major public health threat. PMID:26402569

  10. Staphylococcus aureus colonization related to severity of hand eczema.

    PubMed

    Mernelius, S; Carlsson, E; Henricson, J; Löfgren, S; Lindgren, P-E; Ehricht, R; Monecke, S; Matussek, A; Anderson, C D

    2016-08-01

    Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p < 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES ≥ 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare. PMID:27193891

  11. Methicillin-resistant Staphylococcus non-aureus Infection in an Irradiated Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Kolappaswamy, Krishnan; Shipley, Steven T; Tatarov, Ivan I; DeTolla, Louis J

    2008-01-01

    We describe a case of methicillin-resistant Staphylococcus non-aureus infection in a rhesus macaque (Macaca mulatta). The nonhuman primate described was part of a research project that involved whole-body gamma irradiation and subsequently developed acute generalized dermatitis with skin dryness, peeling, and erythema around the eyes. After initial evaluation, which included microbiologic culture and 6 d of medical treatment, the animal was euthanized due to concern regarding a possible outbreak of infectious or zoonotic disease. On the basis of skin culture, diagnosis of methicillin-resistant Staphylococcus non-aureus was confirmed. This report underscores the importance of the occupational risk of methicillin-resistant Staphylococcus non-aureus to research and animal care staff in a research animal facility setting. PMID:18459716

  12. Necroptosis Promotes Staphylococcus aureus Clearance by Inhibiting Excessive Inflammatory Signaling.

    PubMed

    Kitur, Kipyegon; Wachtel, Sarah; Brown, Armand; Wickersham, Matthew; Paulino, Franklin; Peñaloza, Hernán F; Soong, Grace; Bueno, Susan; Parker, Dane; Prince, Alice

    2016-08-23

    Staphylococcus aureus triggers inflammation through inflammasome activation and recruitment of neutrophils, responses that are critical for pathogen clearance but are associated with substantial tissue damage. We postulated that necroptosis, cell death mediated by the RIPK1/RIPK3/MLKL pathway, would function to limit pathological inflammation. In models of skin infection or sepsis, Mlkl-/- mice had high bacterial loads, an inability to limit interleukin-1b (IL-1b) production, and excessive inflammation. Similarly, mice treated with RIPK1 or RIPK3 inhibitors had increased bacterial loads in a model of sepsis. Ripk3-/- mice exhibited increased staphylococcal clearance and decreased inflammation in skin and systemic infection, due to direct effects of RIPK3 on IL-1b activation and apoptosis. In contrast to Casp1/4-/- mice with defective S. aureus killing, the poor outcomes of Mlkl-/- mice could not be attributed to impaired phagocytic function. We conclude that necroptotic cell death limits the pathological inflammation induced by S. aureus. PMID:27524612

  13. Destruction of Staphylococcus aureus during frankfurter processing.

    PubMed Central

    Palumbo, S A; Smith, J L; Kissinger, J C

    1977-01-01

    We studied the thermal resistance of Staphylococcus aureus during frankfurter processing in respect to whether staphylococci are killed by the heating step of the process and whether heat injury interferes with the quantitative estimation of the survivors. With S. aureus 198E, heat injury could be demonstrated only when large numbers of cells (10(8)/g) were present and at a product temperature of 140 degrees F (60 degrees C). On tryptic soy agar and tryptic soy agar plus 7% NaCl media, at temperatures less than 140 degrees F, the counts were virtually identical; above 140 degrees F, the counts converged, with the organisms dying so rapidly that heat injury was not demonstrable. Heat injury was thus judged not to interfere with the quantitative estimation of staphylococci surviving the normal commercial heating given frankfurters. By using a combination of direct plating on tryptic soy agar and a most-probable-number technique, we detected no viable cells (less than 0.3/g) of several strains of S. aureus in frankfurters heated to 160 degrees F (71.1 degrees C). This temperature is compatible with the normal final temperature to which federally inspected processors heat their frankfurters and with the temperature needed to destroy salmonellae. PMID:563701

  14. NVC-422 Inactivates Staphylococcus aureus Toxins

    PubMed Central

    Jekle, Andreas; Yoon, Jungjoo; Zuck, Meghan; Najafi, Ramin; Wang, Lu; Shiau, Timothy; Francavilla, Charles; Rani, Suriani Abdul; Eitzinger, Christian; Nagl, Markus; Anderson, Mark

    2013-01-01

    Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the host or gaining entry into host cells. They can cause pathogenesis by inhibiting or stimulating certain host functions. For example, in systemic Staphylococcus aureus infections, virulence factors such as toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB) cause sepsis or toxic shock by uncontrolled stimulation of T lymphocytes and by triggering a cytokine storm. In vitro, these superantigens stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and the release of many cytokines. NVC-422 (N,N-dichloro-2,2-dimethyltaurine) is a broad-spectrum, fast-acting topical anti-infective agent against microbial pathogens, including antibiotic-resistant microbes. Using mass spectrometry, we demonstrate here that NVC-422 oxidizes methionine residues of TSST-1, SEA, SEB, and exfoliative toxin A (ETA). Exposure of virulence factors to 0.1% NVC-422 for 1 h prevented TSST-1-, SEA-, SEB-, and ETA-induced cell proliferation and cytokine release. Moreover, NVC-422 also delayed and reduced the protein A- and clumping factor-associated agglutination of S. aureus cultures. These results show that, in addition to its well-described direct microbicidal activity, NVC-422 can inactivate S. aureus virulence factors through rapid oxidation of methionines. PMID:23208720

  15. Essential Staphylococcus aureus toxin export system

    PubMed Central

    Chatterjee, Som S.; Joo, Hwang-Soo; Duong, Anthony C.; Dieringer, Thomas D.; Tan, Vee Y.; Song, Yan; Fischer, Elizabeth R.; Cheung, Gordon Y. C.; Li, Min; Otto, Michael

    2012-01-01

    Widespread antibiotic resistance among important bacterial pathogens such as Staphylococcus aureus1 calls for alternative routes of drug development. Interfering with critical virulence determinants is considered a promising novel approach to control bacterial infection2. Phenol-soluble modulins (PSMs) are peptide toxins with multiple key roles in pathogenesis3–5 and a major impact on the ability of highly virulent S. aureus to cause disease3,6. However, targeting PSMs for therapeutic intervention is hampered by their multitude and diversity. Here, we report that an ABC transporter with previously unknown function is responsible for the export of all PSM classes, thus representing a single target to interfere simultaneously with the production of all PSMs. The transporter had a strong effect on virulence phenotypes, such as neutrophil lysis, and the development of S. aureus infection, similar in extent to the sum of all PSMs. Furthermore, it proved essential for bacterial growth. Moreover, it protected the producer from the antimicrobial activity of secreted PSMs and contributed to defense against PSM-mediated bacterial interference. Our study reveals a non-canonical, dedicated secretion mechanism for an important toxin class and identifies this mechanism as a comprehensive potential target for the development of drugs efficiently inhibiting growth and virulence of pathogenic staphylococci. PMID:23396209

  16. Toxin-Antitoxin Systems of Staphylococcus aureus.

    PubMed

    Schuster, Christopher F; Bertram, Ralph

    2016-01-01

    Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery. PMID:27164142

  17. Immunopathogenesis of Staphylococcus aureus pulmonary infection

    PubMed Central

    Parker, Dane; Prince, Alice

    2013-01-01

    Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID:22037948

  18. agr function in clinical Staphylococcus aureus isolates

    PubMed Central

    Traber, Katrina E.; Lee, Elsie; Benson, Sarah; Corrigan, Rebecca; Cantera, Mariela; Shopsin, Bo; Novick, Richard P.

    2016-01-01

    The accessory gene regulator (agr) of Staphylococcus aureus is a global regulator of the staphylococcal virulon, which includes secreted virulence factors and surface proteins. The agr locus is important for virulence in a variety of animal models of infection, and has been assumed by inference to have a major role in human infection. Although most human clinical S. aureus isolates are agr+, there have been several reports of agr-defective mutants isolated from infected patients. Since it is well known that the agr locus is genetically labile in vitro, we have addressed the question of whether the reported agr-defective mutants were involved in the infection or could have arisen during post-isolation handling. We obtained a series of new staphylococcal isolates from local clinical infections and handled these with special care to avoid post-isolation mutations. Among these isolates, we found a number of strains with non-haemolytic phenotypes owing to mutations in the agr locus, and others with mutations elsewhere. We have also obtained isolates in which the population was continuously heterogeneous with respect to agr functionality, with agr+ and agr− variants having otherwise indistinguishable chromosomal backgrounds. This finding suggested that the agr− variants arose by mutation during the course of the infection. Our results indicate that while most clinical isolates are haemolytic and agr+, non-haemolytic and agr− strains are found in S. aureus infections, and that agr+ and agr− variants may have a cooperative interaction in certain types of infections. PMID:18667559

  19. Toxin-Antitoxin Systems of Staphylococcus aureus

    PubMed Central

    Schuster, Christopher F.; Bertram, Ralph

    2016-01-01

    Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery. PMID:27164142

  20. Aspartate inhibits Staphylococcus aureus biofilm formation.

    PubMed

    Yang, Hang; Wang, Mengyue; Yu, Junping; Wei, Hongping

    2015-04-01

    Biofilm formation renders Staphylococcus aureus highly resistant to conventional antibiotics and host defenses. Four D-amino acids (D-Leu, D-Met, D-Trp and D-Tyr) have been reported to be able to inhibit biofilm formation and disassemble established S. aureus biofilms. We report here for the first time that both D- and L-isoforms of aspartate (Asp) inhibited S. aureus biofilm formation on tissue culture plates. Similar biofilm inhibition effects were also observed against other staphylococcal strains, including S. saprophyticus, S. equorum, S. chromogenes and S. haemolyticus. It was found that Asp at high concentrations (>10 mM) inhibited the growth of planktonic N315 cells, but at subinhibitory concentrations decreased the cellular metabolic activity without influencing cell growth. The decreased cellular metabolic activity might be the reason for the production of less protein and DNA in the matrix of the biofilms formed in the presence of Asp. However, varied inhibition efficacies of Asp were observed for biofilms formed by clinical staphylococcal isolates. There might be mechanisms other than decreasing the metabolic activity, e.g. the biofilm phenotypes, affecting biofilm formation in the presence of Asp. PMID:25687923

  1. Staphylococcus pseudintermedius expresses surface proteins that closely resemble those from Staphylococcus aureus.

    PubMed

    Geoghegan, Joan A; Smith, Emma J; Speziale, Pietro; Foster, Timothy J

    2009-09-18

    Staphylococcus pseudintermedius is a commensal of dogs that is implicated in the pathogenesis of canine pyoderma. This study aimed to determine if S. pseudintermedius expresses surface proteins resembling those from Staphylococcus aureus and to characterise them. S. pseudintermedius strain 326 was shown to adhere strongly to purified fibrinogen, fibronectin and cytokeratin 10. It adhered to the alpha-chain of fibrinogen which, along with binding to cytokeratin 10, is the hallmark of clumping factor B of S. aureus, a surface protein that is in part responsible for colonisation of the human nares. Ligand-affinity blotting with cell-wall extracts demonstrated that S. pseudintermedius 326 expressed a cell-wall anchored fibronectin binding protein which recognised the N-terminal 29kDa fragment. The ability to bind fibronectin is an important attribute of pathogenic S. aureus and is associated with the ability of S. aureus to colonise skin of human atopic dermatitis patients. S. pseudintermedius genomic DNA was probed with labelled DNA amplified from the serine-aspartate repeat encoding region of clfA of S. aureus. This probe hybridised to a single SpeI fragment of S. pseudintermedius DNA. In the cell-wall extract of S. pseudintermedius 326, a 180kDa protein was discovered which bound to fibrinogen by ligand-affinity blotting and reacted in a Western blot with antibodies raised against the serine-aspartate repeat region of ClfA and the B-repeats of SdrD of S. aureus. It is proposed that this is an Sdr protein with B-repeats that has an A domain that binds to fibrinogen. Whether it is the same protein that binds cytokeratin 10 is not clear. PMID:19372010

  2. Characterization of Staphylococcus aureus infections in children with Down syndrome.

    PubMed

    Johnston, Jeffrey N; Kaplan, Sheldon L; Mason, Edward O; Hulten, Kristina G

    2015-11-01

    Staphylococcus aureus infections in the Down syndrome (DS) population have not been well characterized. This study determined clinical and molecular characteristics of S. aureus infections in children with DS followed at Texas Children's Hospital (TCH), from 2001 to 2011. Patients were retrospectively identified from an ongoing S. aureus surveillance study. Medical records were reviewed. Isolates were characterized by antimicrobial susceptibility, pulsed-field gel electrophoresis patterns, and detection of PVL genes (pvl), mupA (high-level mupirocin resistance gene), smr (chlorhexidine resistance conferring gene), and Staphylococcal Chromosomal Cassette mec (SCCmec) type. Twenty-six patients with DS had a total of 34 S. aureus infections (8 recurrent); 61% were MRSA. DS patients represented 16.8 per 10,000 community onset S. aureus infections seen at TCH. Among 26 initial infections 17 were skin and soft tissue (SSTI), 7 were outer or middle ear and 2 were invasive infections. Seventeen patients were hospitalized. Thirteen (65%) of 20 available isolates were USA300, 14 were pvl+, 5 were mupA+, and 8 were smr+. Five of 8 (63%) recurrent infections were ear infections. All 4 recurrent ear isolates available for study were smr+, ciprofloxacin non-susceptible and treated with ciprofloxacin otic drops. S. aureus infections among patients with DS were similar in presentation to other patient groups, except for a greater proportion being associated with ear infections. Seventy percent of ear fluid isolates carried antiseptic and fluoroquinolone resistance genes. A study of a greater number of DS patients is warranted to further explore these findings. PMID:26386776

  3. Antibiotic Susceptibility of Staphylococcus aureus in Atopic Dermatitis: Current Prevalence of Methicillin-Resistant Staphylococcus aureus in Korea and Treatment Strategies

    PubMed Central

    Jung, Mi-Young; Chung, Jong-Youn; Lee, Hae-Young; Park, Jiho; Lee, Dong-Youn

    2015-01-01

    Background Staphylococcus aureus is a well-known microbe that colonizes or infects the skin in atopic dermatitis (AD). The prevalence of methicillin-resistant S. aureus (MRSA) in AD has recently been increasing. Objective This study aimed to determine the antimicrobial susceptibility patterns in AD skin lesions and evaluate the prevalence of MRSA in Korea. We also recommend proper first-line topical antibiotics for Korean patients with AD. Methods We studied S. aureus-positive skin swabs (n=583) from the lesional skin of infants, children, and adults who presented to our outpatient clinic with AD from July 2009 to April 2012. Results S. aureus exhibited high susceptibility against most antimicrobial agents. However, it exhibited less susceptibility to benzylpenicillin, erythromycin, clindamycin, and fusidic acid. The prevalence of MRSA was 12.9% among 583 S. aureus isolates, and the susceptibility to oxacillin was significantly lower in infants in both acute and chronic AD lesions. Conclusion S. aureus from AD has a high prevalence of MRSA and multidrug resistance, especially in infants. In addition, the rate of fusidic acid resistance is high among all age groups, and mupirocin resistance increases with age group regardless of lesional status. This is the first study comparing the antimicrobial susceptibility rates of S. aureus isolates from AD cases with respect to age and lesion status in Korea. PMID:26273155

  4. A Tactile Response in Staphylococcus aureus

    PubMed Central

    Lower, Steven K.; Yongsunthon, Ruchirej; Casillas-Ituarte, Nadia N.; Taylor, Eric S.; DiBartola, Alex C.; Lower, Brian H.; Beveridge, Terrance J.; Buck, Andrew W.; Fowler, Vance G.

    2010-01-01

    It is well established that bacteria are able to respond to temporal gradients (e.g., by chemotaxis). However, it is widely held that prokaryotes are too small to sense spatial gradients. This contradicts the common observation that the vast majority of bacteria live on the surface of a solid substrate (e.g., as a biofilm). Herein we report direct experimental evidence that the nonmotile bacterium Staphylococcus aureus possesses a tactile response, or primitive sense of touch, that allows it to respond to spatial gradients. Attached cells recognize their substrate interface and localize adhesins toward that region. Braille-like avidity maps reflect a cell's biochemical sensory response and reveal ultrastructural regions defined by the actual binding activity of specific proteins. PMID:21044577

  5. PENICILLINASE PLASMID DNA FROM Staphylococcus aureus*

    PubMed Central

    Rush, Mark G.; Gordon, C. N.; Novick, Richard P.; Warner, Robert C.

    1969-01-01

    A penicillinase plasmid from Staphylococcus aureus and three of its derivatives, all previously identified as extrachromosomal genetic elements, have been isolated in high yield as circular duplex DNA molecules. The wild-type plasmid was found by contour-length measurements of electron micrographs to have a molecular weight of 18.6 × 106 daltons. Two plasmids with deletions encompassing six and eight of the eleven known plasmid cistrons had molecular weights of 16.4 × 106 and 15.3 × 106 daltons, respectively. This information was used to establish approximate physical distances for the genetic map. A high-frequency transducing element also derived from the plasmid had a molecular weight of approximately 24 × 106 daltons. Although each plasmid preparation appeared homogeneous by ultracentrifugal analysis, electron micrographs always revealed the presence of a low percentage of complex oligomeric forms, particularly circular and catenated dimers. Images PMID:5260933

  6. Methicillin-resistant Staphylococcus aureus, Western Australia

    PubMed Central

    Dailey, Lynne; Coombs, Geoffrey W.; O'Brien, Frances G.; Pearman, John W.; Christiansen, Keryn; Grubb, Warren B.

    2005-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a notable cause of hospital-acquired infections. A statewide screening and control policy was implemented in Western Australia (WA) after an outbreak of epidemic MRSA in a Perth hospital in 1982. We report on statutory notifications from1998 to 2002 and review the 20-year period from 1983 to 2002. The rate of reporting of community-associated Western Australia MRSA (WAMRSA) escalated from 1998 to 2002 but may have peaked in 2001. Several outbreaks were halted, but they resulted in an increase in reports as a result of screening. A notable increase in ciprofloxacin resistance during the study period was observed as a result of more United Kingdom epidemic MRSA (EMRSA) -15 and -16. WA has seen a persistently low incidence of multidrug-resistant MRSA because of the screening and decolonization program. Non–multidrug-resistant, community-associated WAMRSA strains have not established in WA hospitals. PMID:16318700

  7. Clinical Management of Staphylococcus aureus Bacteremia

    PubMed Central

    Holland, Thomas L.; Arnold, Christopher; Fowler, Vance G.

    2014-01-01

    Importance Several management strategies may improve outcomes in patients with Staphylococcus aureus bacteremia (SAB). The strength of evidence supporting these management strategies, however, varies widely. Objective To perform a systematic review of the evidence for two unresolved questions involving management strategies for SAB: 1) is transesophageal echocardiography (TEE) necessary in all cases of SAB; and 2) what is the optimal antibiotic therapy for methicillin resistant Staphylococcus aureus (MRSA) bacteremia? Evidence acquisition A PubMed search from inception through May 2014 was performed to find studies that addressed the role of TEE in SAB. A second search of PubMed, EMBASE, and The Cochrane Library from 1/1/1990 to 5/28/2014 was performed to find studies that addressed antibiotic treatment of MRSA bacteremia. Studies that reported outcomes of systemic antibiotic therapy for MRSA bacteremia were included. All searches were augmented by review of bibliographic references from included studies. The quality of evidence was assessed using the GRADE system by consensus of independent evaluations by at least two authors. Results In 9 studies with a total of 3513 patients, use of TEE was associated with higher rates of diagnosis of endocarditis (14–25%) when compared with TTE (2–14%). Five studies proposed criteria to identify patients in whom TEE might safely be avoided. Only one high-quality trial of antibiotic therapy for MRSA bacteremia was identified from the 83 studies considered. Conclusions and relevance Most contemporary management strategies for SAB are based upon low quality evidence. TEE is indicated in most patients with SAB. It may be possible to identify a subset of SAB patients for whom TEE can be safely avoided. Vancomycin and daptomycin are the first-line antibiotic choices for MRSA bacteremia. Well-designed studies to address the management of SAB are desperately needed. PMID:25268440

  8. Where does a Staphylococcus aureus vaccine stand?

    PubMed

    Fowler, V G; Proctor, R A

    2014-05-01

    In this review, we examine the current status of Staphylococcus aureus vaccine development and the prospects for future vaccines. Examination of the clinical trials to date show that murine models have not predicted success in humans for active or passive immunization. A key factor in the failure to develop a vaccine to prevent S. aureus infections comes from our relatively limited knowledge of human protective immunity. More recent reports on the elements of the human immune response to staphylococci are analysed. In addition, there is some controversy concerning the role of antibodies for protecting humans, and these data are reviewed. From a review of the current state of understanding of staphylococcal immunity, a working model is proposed. Some new work has provided some initial candidate biomarker(s) to predict outcomes of invasive infections and to predict the efficacy of antibiotic therapy in humans. We conclude by looking to the future through the perspective of lessons gleaned from the clinical vaccine trials. PMID:24476315

  9. Tryptophan biosynthetic enzymes of Staphylococcus aureus.

    PubMed

    Proctor, A R; Kloos, W E

    1973-04-01

    Tryptophan biosynthetic enzymes were assayed in various tryptophan mutants of Staphylococcus aureus strain 655 and the wild-type parent. All mutants, except trpB mutants, lacked only the activity corresponding to the particular biosynthetic block, as suggested previously by analysis of accumulated intermediates and auxonography. Tryptophan synthetase A was not detected in extracts of either trpA or trpB mutants but appeared normal in other mutants. Mutants in certain other classes exhibited partial loss of another particular tryptophan enzyme activity. Tryptophan synthetase B activity was not detected in cell extract preparations but was detected in whole cells. The original map order proposed for the S. aureus tryptophan gene cluster was clarified by the definition of trpD (phosphoribosyl transferase(-)) and trpF (phosphoribosyl anthranilate isomerase(-)) mutants. These mutants were previously unresolved and designated as trp(DF) mutants (anthranilate accumulators). Phosphoribosyl anthranilate isomerase and indole-3-glycerol phosphate synthetase enzymes were separable by molecular sieve chromatography, suggesting that these functions are coded by separate loci. Molecular sieve chromatography failed to reveal aggregates involving anthranilate synthetase, phosphoribosyl transferase, phosphoribosyl anthranilate isomerase, and indole-3-glycerol phosphate synthetase, and this procedure provided an estimate of the molecular weights of these enzymes. Tryptophan was shown to repress synthesis of all six tryptophan biosynthetic enzymes, and derepression of all six activities was incident upon tryptophan starvation. Tryptophan inhibited the activity of anthranilate synthetase, the first enzyme of the pathway. PMID:4698207

  10. Alpha-toxin promotes Staphylococcus aureus mucosal biofilm formation.

    PubMed

    Anderson, Michele J; Lin, Ying-Chi; Gillman, Aaron N; Parks, Patrick J; Schlievert, Patrick M; Peterson, Marnie L

    2012-01-01

    Staphylococcus aureus causes many diseases in humans, ranging from mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS). S. aureus may be asymptomatically carried in the anterior nares or vagina or on the skin, serving as a reservoir for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and the leading cause of TSS. The cytolysin α-toxin (also known as α-hemolysin or Hla) is the major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. The current study aims to characterize the differences between TSS USA200 strains [high (hla(+)) and low (hla(-)) α-toxin producers] in their ability to disrupt vaginal mucosal tissue and to characterize the subsequent infection. Tissue viability post-infection and biofilm formation of TSS USA200 isolates CDC587 and MN8, which contain the α-toxin pseudogene (hla(-)), MNPE (hla(+)), and MNPE isogenic hla knockout (hlaKO), were observed via LIVE/DEAD® staining and confocal microscopy. All TSS strains grew to similar bacterial densities (1-5 × 10(8) CFU) on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587 (hla(-)), MN8 (hla(-)), nor MNPE hlaKO formed biofilms. The latter strains were also less cytotoxic than wild-type MNPE. The addition of exogenous, purified α-toxin to MNPE hlaKO restored the biofilm phenotype. We speculate that α-toxin affects S. aureus phenotypic growth on vaginal mucosa by promoting tissue disruption and biofilm formation. Further, α-toxin mutants (hla(-)) are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic variants (HDPV). PMID:22919655

  11. Global Gene Expression in Staphylococcus aureus Biofilms

    PubMed Central

    Beenken, Karen E.; Dunman, Paul M.; McAleese, Fionnuala; Macapagal, Daphne; Murphy, Ellen; Projan, Steven J.; Blevins, Jon S.; Smeltzer, Mark S.

    2004-01-01

    We previously demonstrated that mutation of the staphylococcal accessory regulator (sarA) in a clinical isolate of Staphylococcus aureus (UAMS-1) results in an impaired capacity to form a biofilm in vitro (K. E. Beenken, J. S. Blevins, and M. S. Smeltzer, Infect. Immun. 71:4206-4211, 2003). In this report, we used a murine model of catheter-based biofilm formation to demonstrate that a UAMS-1 sarA mutant also has a reduced capacity to form a biofilm in vivo. Surprisingly, mutation of the UAMS-1 ica locus had little impact on biofilm formation in vitro or in vivo. In an effort to identify additional loci that might be relevant to biofilm formation and/or the adaptive response required for persistence of S. aureus within a biofilm, we isolated total cellular RNA from UAMS-1 harvested from a biofilm grown in a flow cell and compared the transcriptional profile of this RNA to RNA isolated from both exponential- and stationary-phase planktonic cultures. Comparisons were done using a custom-made Affymetrix GeneChip representing the genomic complement of six strains of S. aureus (COL, N315, Mu50, NCTC 8325, EMRSA-16 [strain 252], and MSSA-476). The results confirm that the sessile lifestyle associated with persistence within a biofilm is distinct by comparison to the lifestyles of both the exponential and postexponential phases of planktonic culture. Indeed, we identified 48 genes in which expression was induced at least twofold in biofilms over expression under both planktonic conditions. Similarly, we identified 84 genes in which expression was repressed by a factor of at least 2 compared to expression under both planktonic conditions. A primary theme that emerged from the analysis of these genes is that persistence within a biofilm requires an adaptive response that limits the deleterious effects of the reduced pH associated with anaerobic growth conditions. PMID:15231800

  12. Molecular Characterization of Staphylococcus aureus Isolates Transmitted between Patients with Buruli Ulcer

    PubMed Central

    Amissah, Nana Ama; Chlebowicz, Monika A.; Ablordey, Anthony; Sabat, Artur J.; Tetteh, Caitlin S.; Prah, Isaac; van der Werf, Tjip S.; Friedrich, Alex W.; van Dijl, Jan Maarten

    2015-01-01

    Background Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. Methodology This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere+ software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. Principal Findings SeqSphere+ analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus. PMID:26360794

  13. Outbreak of Skin Infections Due to Panton-Valentine Leukocidin-Positive Methicillin-Susceptible Staphylococcus aureus in a French Prison in 2010-2011

    PubMed Central

    Bourigault, Céline; Corvec, Stéphane; Brulet, Virginie; Robert, Pierre-Yves; Mounoury, Olivier; Goubin, Chloé; Boutoille, David; Hubert, Bruno; Bes, Michèle; Tristan, Anne; Etienne, Jérôme; Lepelletier, Didier

    2014-01-01

    Background. An outbreak of PVL-positive MSSA skin and soft tissue-infections (SSTIs) was suspected in May 2010 when recurrent SSTI was diagnosed in an inmate of a large prison in Nantes, France. Methods and findings. Retrospective and prospective investigations were performed. Microbiological characterisation was by DNA microarray testing (S. aureus genotyping - Identibac, Alere). We identified 14 inmates meeting our clinical and microbiological case definition for PVL-MSSA SSTI between March 2010 and April 2011. The SSTIs developed in tattooed areas in 4 patients and in areas shaved daily with a mechanical razor in 4 other patients. All case isolates exhibited a similar SmaI pulsed-field gel electrophoresis pattern. Microarray analysis showed that all 14 isolates harboured genes encoding PVL and enterotoxins (A, H, K, and Q) and belonged to clonal complex 1 (CC1). Individual and collective hygiene measures, education delivered to inmates and prison employees, and antibiotic treatment of SSTIs were successful in controlling the outbreak. No new cases were identified after April 2011. Routine screening for PVL-positive MSSA carriage was not feasible. Conclusions. Our data suggest that tattooing and shaving with mechanical razors may constitute risk factors for SSTIs among previously colonised inmates and contribute to the PVL-MSSA outbreak in the prison. Allowing inmates access to professional tattooists and to the hygiene and safety conditions available to people in the community would help to prevent tattoo-related infections. PMID:24619564

  14. Outbreak of Skin Infections Due to Panton-Valentine Leukocidin-Positive Methicillin-Susceptible Staphylococcus aureus in a French Prison in 2010-2011.

    PubMed

    Bourigault, Céline; Corvec, Stéphane; Brulet, Virginie; Robert, Pierre-Yves; Mounoury, Olivier; Goubin, Chloé; Boutoille, David; Hubert, Bruno; Bes, Michèle; Tristan, Anne; Etienne, Jérôme; Lepelletier, Didier

    2014-01-01

    Background. An outbreak of PVL-positive MSSA skin and soft tissue-infections (SSTIs) was suspected in May 2010 when recurrent SSTI was diagnosed in an inmate of a large prison in Nantes, France. Methods and findings. Retrospective and prospective investigations were performed. Microbiological characterisation was by DNA microarray testing (S. aureus genotyping - Identibac, Alere). We identified 14 inmates meeting our clinical and microbiological case definition for PVL-MSSA SSTI between March 2010 and April 2011. The SSTIs developed in tattooed areas in 4 patients and in areas shaved daily with a mechanical razor in 4 other patients. All case isolates exhibited a similar SmaI pulsed-field gel electrophoresis pattern. Microarray analysis showed that all 14 isolates harboured genes encoding PVL and enterotoxins (A, H, K, and Q) and belonged to clonal complex 1 (CC1). Individual and collective hygiene measures, education delivered to inmates and prison employees, and antibiotic treatment of SSTIs were successful in controlling the outbreak. No new cases were identified after April 2011. Routine screening for PVL-positive MSSA carriage was not feasible. Conclusions. Our data suggest that tattooing and shaving with mechanical razors may constitute risk factors for SSTIs among previously colonised inmates and contribute to the PVL-MSSA outbreak in the prison. Allowing inmates access to professional tattooists and to the hygiene and safety conditions available to people in the community would help to prevent tattoo-related infections. PMID:24619564

  15. Clearance of experimental cutaneous Staphylococcus aureus infections in mice

    PubMed Central

    Onunkwo, Charles C.; Hahn, Beth L.

    2010-01-01

    Staphylococcal skin infections are quite common in human patients. These infections often clear spontaneously, but may also progress locally and/or disseminate to cause serious and sometimes fatal deep infections. The present studies were undertaken to examine the clearance phase of experimental cutaneous Staphylococcus aureus infections in a mouse model system. Previous work in this system has shown that staphylococci applied to the skin rapidly disseminate to the spleen and kidney. In the present experiments the bacteria were found to persist at the skin infection site at a time (8 days after inoculation) when they had disappeared from the spleen and kidney. Examination of the infected skin at earlier times revealed rapid (within 6 h) invasion into the stratum corneum, stratum Malpighii, and dermis, but subsequent redistribution of bacteria (at 1–2 days) to more superficial sites, particularly crusts located just above the skin surface. The crusts seen in these infections were of two distinct types, which were termed type 1 and type 2. Type 1 crusts appeared first, consisted of bacteria, inflammatory cells, and debris, and developed over an intact epidermis. Type 2 crusts arose from the process of dermal necrosis previously reported to take place at 2 days in this model system. In the latter situation the bacteria were not really cleared from the epidermis and dermis; rather those layers were transformed into a superficial crust that contained the bacteria. Deep hair follicle infections in the dermis were found in these infections, but they did not persist and did not seem to be a reservoir for organisms in the dermis. Resolution of these experimental infections appeared to involve redistribution of invading bacteria to more superficial locations in crusts above the skin surface, marked proliferation of the epidermis, loss of the bacteria-laden crusts from the skin, and eventual healing of the cutaneous damage. PMID:20130894

  16. Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus

    PubMed Central

    Trouillet-Assant, Sophie; Riffard, Natacha; Tasse, Jason; Flammier, Sacha; Rasigade, Jean-Philippe; Chidiac, Christian; Vandenesch, François; Ferry, Tristan; Laurent, Frédéric

    2015-01-01

    Although Staphylococcus aureus persistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in an ex vivo osteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001 S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of −2.5, −3.1, −3.9, −4.2, −4.9, −4.9, and −5.2 log10 CFU/100,000 cells, respectively (P < 10−4). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin. PMID:25605365

  17. Agglutinating serum for distinguishing Staphylococcus aureus of human biotype.

    PubMed

    Live, I

    1975-08-01

    Antiserum to Staphylococcus aureus strain 17 was treated with S. aureus strain 61218 until the antibodies against thermostable agglutinogen were removed. The absorbed serum agglutinated phage-typable as well as phageuntypable staphylococci of human biotype, whether recovered from people or from dogs. PMID:125241

  18. Staphylococcus aureus colonization in healthy horses in Atlantic Canada

    PubMed Central

    Burton, Shelly; Reid-Smith, Richard; McClure, J. Trenton; Weese, J. Scott

    2008-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonization was not identified in any of 497 horses from Atlantic Canada. Methicillin-susceptible S. aureus (MSSA) was isolated from a subsample of 19/242 (7.9%) horses. Colonization with MSSA is relatively common in healthy horses in Atlantic Canada, but MRSA is currently rare or absent. PMID:18978975

  19. Internet Queries and Methicillin-Resistant Staphylococcus aureus Surveillance

    PubMed Central

    Dukic, Vanja M.; David, Michael Z.

    2011-01-01

    The Internet is a common source of medical information and has created novel surveillance opportunities. We assessed the potential for Internet-based surveillance of methicillin-resistant Staphylococcus aureus and examined the extent to which it reflects trends in hospitalizations and news coverage. Google queries were a useful predictor of hospitalizations for methicillin-resistant S. aureus infections. PMID:21749772

  20. Lysostaphin in treatment of neonatal Staphylococcus aureus infection.

    PubMed

    Oluola, Okunola; Kong, Lingkun; Fein, Mindy; Weisman, Leonard E

    2007-06-01

    This study describes lysostaphin's effect against methicillin-sensitive Staphylococcus aureus in suckling rats. Standard techniques determined minimal inhibitory and bactericidal concentrations, pharmacokinetics, and efficacy. The numbers of surviving rats after vancomycin, oxacillin, and lysostaphin treatment were comparable and were different from that of controls (P < 0.00001). Lysostaphin appears effective in the treatment of neonatal S. aureus infection. PMID:17420212

  1. Molecular dynamics of Staphylococcus aureus nasal carriage in Hajj pilgrims.

    PubMed

    Verhoeven, P O; Gautret, P; Haddar, C H; Benkouiten, S; Gagnaire, J; Belhouchat, K; Grattard, F; Charrel, R; Pozzetto, B; Drali, T; Lucht, F; Brouqui, P; Memish, Z A; Berthelot, P; Botelho-Nevers, E

    2015-07-01

    During the 2012 Hajj season, the risk of acquisition of Staphylococcus aureus nasal carriage in a cohort of French pilgrims was 22.8%, and was statistically associated with the acquisition of viral respiratory pathogens (p 0.03). The carriage of S. aureus belonging to the emerging clonal complex 398 significantly increased following the pilgrimage (p < 0.05). PMID:25882367

  2. Skin tissue engineering for the infected wound site: biodegradable PLA nanofibers and a novel approach for silver ion release evaluated in a 3D coculture system of keratinocytes and Staphylococcus aureus.

    PubMed

    Mohiti-Asli, Mahsa; Pourdeyhimi, Behnam; Loboa, Elizabeth G

    2014-10-01

    Wound infection presents a challenging and growing problem. With the increased prevalence and growth of multidrug-resistant bacteria, there is a mounting need to reduce and eliminate wound infections using methodologies that limit the ability of bacteria to evolve into further drug-resistant strains. A well-known strategy for combating bacterial infection and preventing wound sepsis is through the delivery of silver ions to the wound site. High surface area silver nanoparticles (AgNPs) allowing extensive silver ion release have therefore been explored in different wound dressings and/or skin substitutes. However, it has been recently shown that AgNPs can penetrate into the stratum corneum of skin or diffuse into the cellular plasma membrane, and may interfere with a variety of cellular mechanisms. The goal of this study was to introduce and evaluate a new type of high surface area metallic silver in the form of highly porous silver microparticles (AgMPs). Polylactic acid (PLA) nanofibers were successfully loaded with either highly porous AgMPs or AgNPs and the antimicrobial efficacy and cytotoxicity of the two silver-based wound dressings were assessed and compared. To better mimic the physiological environment in vivo where both human cells and bacteria are present, a novel coculture system combining human epidermal keratinocytes and Staphylococcus aureus bacteria was designed to simultaneously evaluate human skin cell cytotoxicity with antimicrobial efficacy in a three-dimensional environment. We found that highly porous AgMPs could be successfully incorporated in nanofibrous wound dressings, and exhibited comparable antimicrobial efficacy and cytotoxicity to AgNPs. Further, PLA nanofibers containing highly porous AgMPs exhibited steady silver ion release, at a greater rate of release, than nanofibers containing AgNPs. The replacement of AgNPs with the newly introduced AgMPs overcomes concerns regarding the use of nanoparticles and holds great promise as skin

  3. Skin Tissue Engineering for the Infected Wound Site: Biodegradable PLA Nanofibers and a Novel Approach for Silver Ion Release Evaluated in a 3D Coculture System of Keratinocytes and Staphylococcus aureus

    PubMed Central

    Mohiti-Asli, Mahsa; Pourdeyhimi, Behnam

    2014-01-01

    Wound infection presents a challenging and growing problem. With the increased prevalence and growth of multidrug-resistant bacteria, there is a mounting need to reduce and eliminate wound infections using methodologies that limit the ability of bacteria to evolve into further drug-resistant strains. A well-known strategy for combating bacterial infection and preventing wound sepsis is through the delivery of silver ions to the wound site. High surface area silver nanoparticles (AgNPs) allowing extensive silver ion release have therefore been explored in different wound dressings and/or skin substitutes. However, it has been recently shown that AgNPs can penetrate into the stratum corneum of skin or diffuse into the cellular plasma membrane, and may interfere with a variety of cellular mechanisms. The goal of this study was to introduce and evaluate a new type of high surface area metallic silver in the form of highly porous silver microparticles (AgMPs). Polylactic acid (PLA) nanofibers were successfully loaded with either highly porous AgMPs or AgNPs and the antimicrobial efficacy and cytotoxicity of the two silver-based wound dressings were assessed and compared. To better mimic the physiological environment in vivo where both human cells and bacteria are present, a novel coculture system combining human epidermal keratinocytes and Staphylococcus aureus bacteria was designed to simultaneously evaluate human skin cell cytotoxicity with antimicrobial efficacy in a three-dimensional environment. We found that highly porous AgMPs could be successfully incorporated in nanofibrous wound dressings, and exhibited comparable antimicrobial efficacy and cytotoxicity to AgNPs. Further, PLA nanofibers containing highly porous AgMPs exhibited steady silver ion release, at a greater rate of release, than nanofibers containing AgNPs. The replacement of AgNPs with the newly introduced AgMPs overcomes concerns regarding the use of nanoparticles and holds great promise as skin

  4. Methicillin resistant Staphylococcus aureus (MRSA) in India: Prevalence & susceptibility pattern

    PubMed Central

    Joshi, Sangeeta; Ray, Pallab; Manchanda, Vikas; Bajaj, Jyoti; Chitnis, D.S.; Gautam, Vikas; Goswami, Parijath; Gupta, Varsha; Harish, B.N.; Kagal, Anju; Kapil, Arti; Rao, Ratna; Rodrigues, Camilla; Sardana, Raman; Devi, Kh Sulochana; Sharma, Anita; Balaji, Veeragaghavan

    2013-01-01

    Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA) is endemic in India and is a dangerous pathogen for hospital acquired infections. This study was conducted in 15 Indian tertiary care centres during a two year period from January 2008 to December 2009 to determine the prevalence of MRSA and susceptibility pattern of S. aureus isolates in India. Methods: All S. aureus isolates obtained during the study period in the participating centres were included in the study. Each centre compiled their data in a predefined template which included data of the antimicrobial susceptibility pattern, location of the patient and specimen type. The data in the submitted templates were collated and analysed. Results: A total of 26310 isolates were included in the study. The overall prevalence of methicillin resistance during the study period was 41 per cent. Isolation rates for MRSA from outpatients, ward inpatients and ICU were 28, 42 and 43 per cent, respectively in 2008 and 27, 49 and 47 per cent, respectively in 2009. The majority of S. aureus isolates was obtained from patients with skin and soft tissue infections followed by those suffering from blood stream infections and respiratory infections. Susceptibility to ciprofloxacin was low in both MSSA (53%) and MRSA (21%). MSSA isolates showed a higher susceptibility to gentamicin, co-trimoxazole, erythromycin and clindamycin as compared to MRSA isolates. No isolate was found resistant to vancomycin or linezolid. Interpretation & conclusions: The study showed a high level of MRSA in our country. There is a need to study epidemiology of such infections. Robust antimicrobial stewardship and strengthened infection control measures are required to prevent spread and reduce emergence of resistance. PMID:23563381

  5. Predictors of Mortality in Staphylococcus aureus Bacteremia

    PubMed Central

    Jensen, Slade O.; Vaska, Vikram L.; Espedido, Björn A.; Paterson, David L.; Gosbell, Iain B.

    2012-01-01

    Summary: Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes. PMID:22491776

  6. Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model.

    PubMed

    Kim, Choon K; Karau, Melissa J; Greenwood-Quaintance, Kerryl E; Tilahun, Ashenafi Y; Krogman, Ashton; David, Chella S; Pritt, Bobbi S; Patel, Robin; Rajagopalan, Govindarajan

    2015-12-01

    Staphylococcus aureus, the most common cause of wound infection, produces several exotoxins, including superantigens (SAgs). SAgs are the potent activators of the immune system. Given this unique property, we hypothesized that SAgs produced by S. aureus in wounds would have local, as well as systemic immunologic effects. We tested our hypothesis using a novel staphylococcal skin wound infection model in transgenic mice expressing HLA-DR3. Skin wounds were left uninfected or colonized with S. aureus strains producing SAgs or an isogenic strain not producing any SAg. Animals with wounds challenged with SAg-producing S. aureus had increased morbidity and lower serum IL-17 levels compared to those challenged with the SAg non-producing S. aureus (p = 0.027 and p = 0.032, respectively). At Day 8 following microbial challenge, compared to mice with uninfected wounds, the proportion of Vβ8⁺CD4⁺ T cells was increased, while the proportion of Vβ8⁺CD8⁺ T cells was decreased only in the spleens of mice challenged with SAg-producing S. aureus (p < 0.001). No such changes were measured in mice challenged with SAg non-producing S. aureus. Lungs, livers and kidneys from mice challenged with SAg-producing, but not SAg non-producing, S. aureus showed inflammatory changes. Overall, SAg-mediated systemic immune activation in wounds harboring S. aureus may have clinical implications. PMID:26670252

  7. Staphylococcus aureus subsp. anaerobius strain ST1464 genome sequence

    PubMed Central

    Elbir, Haitham; Robert, Catherine; Nguyen, Ti Thien; Gimenez, Grégory; El Sanousi, Sulieman M.; Flock, Jan-Ingmar; Raoult, Didier

    2013-01-01

    Staphylococcus aureus subsp. anaerobius is responsible for Morel's disease in animals and a cause of abscess in humans. It is characterized by a microaerophilic growth, contrary to the other strains of S. aureus. The 2,604,446-bp genome (32.7% GC content) of S. anaerobius ST1464 comprises one chromosome and no plasmids. The chromosome contains 2,660 open reading frames (ORFs), 49 tRNAs and three complete rRNAs, forming one complete operon. The size of ORFs ranges between 100 to 4,600 bp except for two ORFs of 6,417 and 7,173 bp encoding segregation ATPase and non-ribosomal peptide synthase, respectively. The chromosome harbors Staphylococcus phage 2638A genome and incomplete Staphylococcus phage genome PT1028, but no detectable CRISPRS. The antibiotic resistance gene for tetracycline was found although Staphylococcus aureus subsp. anaerobius is susceptible to tetracycline in-vitro. Intact oxygen detoxification genes encode superoxide dismutase and cytochrome quinol oxidase whereas the catalase gene is impaired by a stop codon. Based on the genome, in-silico multilocus sequence typing indicates that S. aureus subsp. anaerobius emerged as a clone separated from all other S. aureus strains, illustrating host-adaptation linked to missing functions. Availability of S. aureus subsp. anaerobius genome could prompt the development of post-genomic tools for its rapid discrimination from S. aureus. PMID:24501641

  8. Evaluation of RapiDEC Staph for identification of Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus.

    PubMed Central

    Janda, W M; Ristow, K; Novak, D

    1994-01-01

    RapiDEC Staph is a test for presumptive identification of the principal human staphylococcal species, Staphylococcus aureus, S. epidermidis, and S. saprophyticus. The test includes control and test cupules for fluorogenic detection of coagulase and chromogenic substrates for alkaline phosphatase and beta-galactosidase. These tests identify S. aureus, S. epidermidis, and S. saprophyticus, respectively. Positive results with both chromogenic substrates provide a presumptive identification of S. xylosus or S. intermedius (S. xylosus-S. intermedius). Test cupules are inoculated with an organism suspension, and reactions are read after a 2-h incubation. RapiDEC-Staph was evaluated with 303 clinical and stock staphylococcal strains. Identifications were compared with those obtained by the tube coagulase test, a latex slide coagulase test (StaphAUREX), another commercial identification system (Staph-TRAC), and additional conventional tests. RapiDEC-Staph correctly identified 100% of 130 S. aureus strains, 70.3% of 74 S. epidermidis strains, and 81.3% of 32 S. saprophyticus strains. Four of five S. xylosus isolates were called S. xylosus-S. intermedius. Unidentified S. epidermidis and S. saprophyticus strains were called "Staphylococcus spp." Among the 62 other coagulase-negative staphylococci, 4 were misidentified as S. epidermidis and 7 were misidentified as S. saprophyticus. While the sensitivity and specificity of the fluorogenic coagulase test for S. aureus were 100%, failure to detect alkaline phosphatase activity in several S. epidermidis isolates resulted in fewer correct identifications by the RapiDEC-Staph test for this species. PMID:7814525

  9. Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012.

    PubMed

    Coombs, Geoffrey W; Daly, Denise A; Pearson, Julie C; Nimmo, Graeme R; Collignon, Peter J; McLaws, Mary-Louise; Robinson, James O; Turnidge, John D

    2014-03-01

    In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P<0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P<0.0001), than the mean age of patients with a PVL

  10. Keratinocytes produce IL-6 in response to desmoglein 1 cleavage by Staphylococcus aureus exfoliative toxin A.

    PubMed

    Rolle, Cleo E; Chen, Juan; Pastar, Irena; Cardenas, Tatiana C P; Perez, Roberto; Hower, Suzanne; Ferracci, Franco; Snyder, Richard; Tomic-Canic, Marjana; Plano, Lisa R W

    2013-12-01

    Many skin infections are caused by Staphylococcus aureus, a bacterial pathogen that produces virulence factors associated with these conditions such as exfoliative toxins A and B (ETA, ETB) and the leukotoxin Panton-Valentine leukocidin (PVL). Herein, we examine the potential of skin-infecting S. aureus to produce virulence factors and their impact on the local immune response. Toxin gene profiles were generated from 188 S. aureus isolated as single infecting organisms from skin lesions and demonstrated a higher potential to express ETA, ETB, and PVL than community isolates (p < 0.001). Within the study isolate group, the prevalence of genes encoding PVL was higher among methicillin-resistant S. aureus (MRSA; n = 49), while genes encoding ETs were more prevalent in methicillin-susceptible S. aureus (MSSA; n = 139). When lesion-associated white blood cell (WBC) counts were dichotomized into high- or low-WBC-count-associated bacteria, the gene for ETA was found to be associated with a low WBC count among MSSA (p = 0.001). The ETA-induced mouse model of staphylococcal scalded skin syndrome was used to investigate the link between ETA and cytokine production. Elevated IL-6 levels in the serum and increased expression of IL-6 mRNA in the skin were detected in response to ETA exposure. These findings were recapitulated in vitro using primary human keratinocytes. Thus, S. aureus may influence the local immune response via ETA cleavage of desmoglein 1 and the induction of cutaneous IL-6 expression. PMID:24287883

  11. Bovine Staphylococcus aureus: diagnostic properties of specific media.

    PubMed

    Graber, H U; Pfister, S; Burgener, P; Boss, R; Meylan, M; Hummerjohann, J

    2013-08-01

    As accurate discrimination between Staphylococcus (S.) aureus and NSA (non-S. aureus staphylococci) involved in bovine mastitis is essential in terms of clinical prognosis and outcome, the aim of this study was to reevaluate the classical bacteriological procedures to identify these agents. Various media and the coagulase tube test were investigated using 116 strains of S. aureus and 115 of NSA, all isolated from cows with spontaneous intramammary infections (IMI). Furthermore, 25 NSA reference strains were analyzed. The study demonstrated that a few media were appropriate for differentiating S. aureus from NSA, provided that the staphylococci were isolated from bovine IMI. Evaluation of hemolysis further revealed that double or incomplete hemolysis are specific for S. aureus and are, therefore, a decisive diagnostic criterion. For strains showing complete hemolysis, maximal discrimination between S. aureus and NSA was observed by subculturing them on CHROMagar Staph. aureus. PMID:23548479

  12. Clinical implications of vancomycin heteroresistant and intermediately susceptible Staphylococcus aureus.

    PubMed

    Gomes, Diane M; Ward, Kristina E; LaPlante, Kerry L

    2015-04-01

    Staphylococcus aureus (S. aureus) has proven to be a major pathogen with the emergence of methicillin-resistant S. aureus (MRSA) infections and recently with heteroresistant vancomycin-intermediate S. aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) infections. Although vancomycin is traditionally a first-line and relatively effective antibiotic, its continued use is under question because reports of heteroresistance in S. aureus isolates are increasing. Both hVISA and VISA infections are associated with complicated clinical courses and treatment failures. The prevalence, mechanism of resistance, clinical significance, and laboratory detection of hVISA and VISA infections are not conclusive, making it difficult to apply research findings to clinical situations. We provide an evidence-based review of S. aureus isolates expressing heterogenic and reduced susceptibility to vancomycin. PMID:25884530

  13. Comparative Proteomic Profiling of Atopic Dermatitis Patients Based on History of Eczema Herpeticum Infection and Staphylococcus aureus Colonization

    PubMed Central

    Broccardo, Carolyn J; Mahaffey, Spencer; Schwarz, John; Wruck, Lisa; David, Gloria; Schlievert, Patrick M; Reisdorph, Nichole A; Leung, Donald YM

    2010-01-01

    Background Atopic dermatitis is the most common inflammatory skin disorder in the general population worldwide and the majority of patients are colonized with Staphylococcus aureus. Eczema herpeticum is a disseminated herpes simplex virus infection that occurs in a small subset of patients. Objectives The goal was to conduct proteomic profiling of atopic dermatitis patients based on Staphylococcus aureus colonization status and history of eczema herpeticum. We hoped to identify new biomarkers for improved diagnosis and prediction of eczema herpeticum and Staphylococcus aureus susceptibility, and to generate new hypotheses regarding disease pathogenesis. Methods Skin taping was performed on nonlesional skin of non-atopic controls and on lesional and nonlesional skin of atopic dermatitis patients. Subjects were classified according to history of eczema herpeticum and Staphylococcus aureus colonization. Proteins were analyzed using mass spectrometry; diagnostic groups were compared for statistically significant differences in protein expression. Results Proteins related to the skin barrier (filaggrin-2, corneodesmosin, desmoglein-1, desmocollin-1, and transglutaminase-3) and generation of natural moisturizing factor (arginase-1, caspase-14, gamma-glutamyl cyclotransferase) were expressed at significantly lower levels in lesional versus nonlesional sites of atopic dermatitis patients with and without history of eczema herpeticum; epidermal fatty acid binding protein was expressed at significantly higher levels in patients with methicillin resistant Staphylococcus aureus. Conclusion This non-invasive, semi-quantitative profiling method has revealed novel proteins likely involved in the pathogenesis of atopic dermatitis. The lower expression of skin barrier proteins and enzymes involved in the generation of the natural moisturizing factor could further exacerbate barrier defects and perpetuate water loss from the skin. The greater expression of epidermal fatty acid

  14. Outbreak of Panton-Valentine Leukocidin-Associated Methicillin-Susceptible Staphylococcus aureus Infection in a Rugby Team, France, 2010-2011.

    PubMed

    Couvé-Deacon, Elodie; Tristan, Anne; Pestourie, Nathalie; Faure, Christian; Doffoel-Hantz, Valérie; Garnier, Fabien; Laurent, Frédéric; Lina, Gerard; Ploy, Marie-Cecile

    2016-01-01

    Staphylococcus aureus strains that produce Panton-Valentine leukocidin are known to cause community infections. We describe an outbreak of skin abscesses caused by Panton-Valentine leukocidin-producing methicillin-susceptible S. aureus (clonal complex 121) in a professional rugby team in France during July 2010-February 2011. Eight team members were carriers; 7 had skin abscesses. PMID:26690308

  15. Outbreak of Panton-Valentine Leukocidin–Associated Methicillin-Susceptible Staphylococcus aureus Infection in a Rugby Team, France, 2010–2011

    PubMed Central

    Couvé-Deacon, Elodie; Tristan, Anne; Pestourie, Nathalie; Faure, Christian; Doffoel-Hantz, Valérie; Garnier, Fabien; Laurent, Frédéric; Lina, Gerard

    2016-01-01

    Staphylococcus aureus strains that produce Panton-Valentine leukocidin are known to cause community infections. We describe an outbreak of skin abscesses caused by Panton-Valentine leukocidin–producing methicillin-susceptible S. aureus (clonal complex 121) in a professional rugby team in France during July 2010–February 2011. Eight team members were carriers; 7 had skin abscesses. PMID:26690308

  16. Evaluation of two iodophor teat germicides: activity against Staphylococcus aureus and Streptococcus agalactiae.

    PubMed

    Boddie, R L; Nickerson, S C

    1997-08-01

    Two germicides containing 0.5 and 1% titratable iodine were tested for efficacy against the development of new intramammary infections (IMI) caused by Staphylococcus aureus and Streptococcus agalactiae. The two trials for postmilking teat dip used a model for experimental challenge that was recommended by the National Mastitis Council. The 0.5% iodine formulation reduced new Staph. aureus IMI by 78.2% and reduced new Strep. agalactiae IMI by 73.2%. The 1% iodine product reduced new Staph. aureus IMI by 43.5% and reduced new Strep. agalactiae IMI by 46.4%. No adverse effects on the condition of teat skin or on teat ends were observed over the course of the trials. At the completion of each trial, the teat skin of dipped quarters was characterized as normal, smooth skin that was free from scales, cracks, or chapping; the teat orifice was characterized as smooth without evidence of irritation. PMID:9276825

  17. Alpha-toxin of Staphylococcus aureus.

    PubMed Central

    Bhakdi, S; Tranum-Jensen, J

    1991-01-01

    Alpha-toxin, the major cytotoxic agent elaborated by Staphylococcus aureus, was the first bacterial exotoxin to be identified as a pore former. The protein is secreted as a single-chain, water-soluble molecule of Mr 33,000. At low concentrations (less than 100 nM), the toxin binds to as yet unidentified, high-affinity acceptor sites that have been detected on a variety of cells including rabbit erythrocytes, human platelets, monocytes and endothelial cells. At high concentrations, the toxin additionally binds via nonspecific absorption to lipid bilayers; it can thus damage both cells lacking significant numbers of the acceptor and protein-free artificial lipid bilayers. Membrane damage occurs in both cases after membrane-bound toxin molecules collide via lateral diffusion to form ring-structured hexamers. The latter insert spontaneously into the lipid bilayer to form discrete transmembrane pores of effective diameter 1 to 2 nm. A hypothetical model is advanced in which the pore is lined by amphiphilic beta-sheets, one surface of which interacts with lipids whereas the other repels apolar membrane constitutents to force open an aqueous passage. The detrimental effects of alpha-toxin are due not only to the death of susceptible targets, but also to the presence of secondary cellular reactions that can be triggered via Ca2+ influx through the pores. Well-studied phenomena include the stimulation of arachidonic acid metabolism, triggering of granule exocytosis, and contractile dysfunction. Such processes cause profound long-range disturbances such as development of pulmonary edema and promotion of blood coagulation.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1779933

  18. Comparative genomic analysis of the genus Staphylococcus including Staphylococcus aureus and its newly described sister species Staphylococcus simiae

    PubMed Central

    2012-01-01

    Background Staphylococcus belongs to the Gram-positive low G + C content group of the Firmicutes division of bacteria. Staphylococcus aureus is an important human and veterinary pathogen that causes a broad spectrum of diseases, and has developed important multidrug resistant forms such as methicillin-resistant S. aureus (MRSA). Staphylococcus simiae was isolated from South American squirrel monkeys in 2000, and is a coagulase-negative bacterium, closely related, and possibly the sister group, to S. aureus. Comparative genomic analyses of closely related bacteria with different phenotypes can provide information relevant to understanding adaptation to host environment and mechanisms of pathogenicity. Results We determined a Roche/454 draft genome sequence for S. simiae and included it in comparative genomic analyses with 11 other Staphylococcus species including S. aureus. A genome based phylogeny of the genus confirms that S. simiae is the sister group to S. aureus and indicates that the most basal Staphylococcus lineage is Staphylococcus pseudintermedius, followed by Staphylococcus carnosus. Given the primary niche of these two latter taxa, compared to the other species in the genus, this phylogeny suggests that human adaptation evolved after the split of S. carnosus. The two coagulase-positive species (S. aureus and S. pseudintermedius) are not phylogenetically closest but share many virulence factors exclusively, suggesting that these genes were acquired by horizontal transfer. Enrichment in genes related to mobile elements such as prophage in S. aureus relative to S. simiae suggests that pathogenesis in the S. aureus group has developed by gene gain through horizontal transfer, after the split of S. aureus and S. simiae from their common ancestor. Conclusions Comparative genomic analyses across 12 Staphylococcus species provide hypotheses about lineages in which human adaptation has taken place and contributions of horizontal transfer in pathogenesis. PMID

  19. Healthcare-Associated Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Kumari, Jyoti; Shenoy, Shalini M.; Baliga, Shrikala; Chakrapani, M.; Bhat, Gopalkrishna K.

    2016-01-01

    Objectives: Healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen worldwide and its multidrug resistance is a major concern. This study aimed to determine the clinical characteristics and antibiotic susceptibility profile of healthcare-associated MRSA with emphasis on resistance to macrolide-lincosamide-streptogramin B (MLSB) phenotypes and vancomycin. Methods: This cross-sectional study was carried out between February 2014 and February 2015 across four tertiary care hospitals in Mangalore, South India. Healthcare-associated infections among 291 inpatients at these hospitals were identified according to the Centers for Disease Control and Prevention guidelines. Clinical specimens were collected based on infection type. S. aureus and MRSA isolates were identified and antibiotic susceptibility tests performed using the Kirby-Bauer disk diffusion method. The minimum inhibitory concentration of vancomycin was determined using the Agar dilution method and inducible clindamycin resistance was detected with a double-disk diffusion test (D-test). Results: Out of 291 healthcare-associated S. aureus cases, 88 were MRSA (30.2%). Of these, 54.6% were skin and soft tissue infections. All of the isolates were susceptible to teicoplanin and linezolid. Four MRSA isolates exhibited intermediate resistance to vancomycin (4.6%). Of the MRSA strains, 10 (11.4%) were constitutive MLSB phenotypes, 31 (35.2%) were inducible MLSB phenotypes and 14 (15.9%) were macrolide-streptogramin B phenotypes. Conclusion: Healthcare-associated MRSA multidrug resistance was alarmingly high. In routine antibiotic susceptibility testing, a D-test should always be performed if an isolate is resistant to erythromycin but susceptible to clindamycin. Determination of the minimum inhibitory concentration of vancomycin is necessary when treating patients with MRSA infections. PMID:27226908

  20. Status of vaccine research and development of vaccines for Staphylococcus aureus.

    PubMed

    Giersing, Birgitte K; Dastgheyb, Sana S; Modjarrad, Kayvon; Moorthy, Vasee

    2016-06-01

    Staphylococcus aureus is a highly versatile gram positive bacterium that is resident as an asymptomatic colonizer on the skin and in the nasopharynx of approximately 30% of individuals. Nasopharyngeal colonization is a risk for acquiring S. aureus infections, which can cause a range of clinical symptoms that are commonly associated with skin and soft-tissue infections. The emergence of S. aureus strains that are highly resistant to antimicrobials has recently become a major public health concern. In low-income countries the incidence of S. aureus disease is highest in neonates and children up to one year of age and mortality rates are estimated to be up to 50%. In the United States, S. aureus infection accounts for approximately 300,000 hospitalizations per year. A vaccine against multi-drug resistant S. aureus, therefore, is urgently needed. Two vaccine candidates have previously been evaluated in late-stage clinical trials but have not demonstrated efficacy. At present, one vaccine candidate and two monoclonal antibody are undergoing clinical evaluation in target groups at high risk for S. aureus infection. This review provides an overview of current vaccine development efforts and presents the major technical and regulatory challenges to developing a licensed S. aureus vaccine. PMID:27105559

  1. Decreased susceptibility of Staphylococcus aureus small-colony variants toward human antimicrobial peptides.

    PubMed

    Gläser, Regine; Becker, Karsten; von Eiff, Christof; Meyer-Hoffert, Ulf; Harder, Jürgen

    2014-09-01

    Staphylococcus aureus is a frequent resident of human nose and skin in many individuals, but it is also able to cause a variety of serious infections including those of the skin and soft tissue. There is increasing evidence that particularly persistent, relapsing, and difficult-to-treat infections caused by S. aureus are associated with the formation of the small-colony variant (SCV) phenotype. The aim of this study was to investigate the hypothesis that (i) skin-derived antimicrobial peptides (AMPs) exhibit a reduced activity against SCVs and (ii) that switching into the SCV phenotype may endow S. aureus with a decreased susceptibility toward the killing activity of human stratum corneum. Here, we show that clinically derived S. aureus SCVs are less susceptible to the bactericidal activity of different human skin-derived AMPs as compared with their isogenic corresponding wild-type strains. Similarly, a S. aureus hemB mutant displaying the SCV phenotype was less susceptible to the antimicrobial activity of AMPs than its hemB-complemented mutant. These findings were accompanied by a higher resistance of SCVs to the killing activity of human stratum corneum. Switching into the SCV phenotype may help S. aureus to subvert cutaneous innate defense, thus contributing to the establishment and persistence of infection. PMID:24717245

  2. Zosteriform Staphylococcus aureus Cutaneous Infection: Report of Two Patients With Dermatomal Bacterial Infection.

    PubMed

    Schepp, Elizabeth D; Cohen, Philip R

    2015-01-01

    The aim of this study was to describe cutaneous infections, which are zosteriform in distribution, including two patients with dermatomal Staphylococcus aureus infection. Herpes zoster infectious lesions usually occur in a dermatomal distribution. Other viruses, such as herpes simplex virus, can also appear with zosteriform lesions and closely mimic the clinical presentation of herpes zoster. Additionally, other skin infections, less commonly, are zosteriform. Two patients who developed zosteriform S aureus skin infection are described. A medical literature search for zosteriform dermatomal infections yielded other cutaneous infections with a zosteriform presentation. Two patients had S aureus and methicillin-resistant S aureus infection with skin lesions occupying the T11-T12 dermatomes and the T4 dermatome, respectively. They responded to antibacterial agents and adjuvant therapy. Patients with viral, fungal, and spirochete zosteriform infections are summarized. In addition to varicella-zoster virus infection, zosteriform skin infection can occur with viral (varicella-zoster virus, herpes simplex virus, and Epstein-Barr virus), superficial (dermatophyte), and deep (phaeohyphomycosis and zygomycosis) fungal, and bacterial (S aureus and methicillin-resistant S aureus) infections. These infections should be considered in the differential diagnosis of a zosteriform infection that does not present with the classic clinical picture for herpes zoster or that does not respond to standard treatments for varicellazoster virus. PMID:26861424

  3. Expanded Glucose Import Capability Affords Staphylococcus aureus Optimized Glycolytic Flux during Infection

    PubMed Central

    Vitko, Nicholas P.; Grosser, Melinda R.; Khatri, Dal; Lance, Thurlow R.

    2016-01-01

    ABSTRACT Acquisition of numerous virulence determinants affords Staphylococcus aureus greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation of S. aureus to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing to S. aureus virulence. Specifically, S. aureus has been shown to ferment glycolytic substrates in nonrespiratory environments encountered within the host. Here, we show that S. aureus has acquired unique carbohydrate transporters that facilitate the maximal uptake of host sugars and serve to support nonrespiratory growth in inflamed tissue. The carbohydrate substrates of 11 S. aureus transporters were identified, and at least four of their genes encode S. aureus glucose transporters (glcA, glcB, glcC, and glcU). Moreover, two transporter genes (glcA and glcC) are unique to S. aureus and contribute disproportionately to the nonrespiratory growth of S. aureus on glucose. Targeted inactivation of sugar transporters reduced glucose uptake and attenuated S. aureus in a murine model of skin and soft tissue infections. These data expand the evidence for metabolic adaptation of S. aureus to invasive infection and demonstrate the specific requirement for the fermentation of glucose over all other available carbohydrates. Ultimately, acquisition of foreign genes allows S. aureus to adopt a metabolic strategy resembling that of infiltrating host immune cells: high glycolytic flux coupled to lactate excretion. PMID:27329749

  4. Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection

    PubMed Central

    Kim, Min-Ho; Yamayoshi, Itsukyo; Mathew, Steven; Liln, Hubert; Nayfach, Joseph; Simon, Scott I.

    2013-01-01

    The incidence of wound infections that do not adequately respond to standard-of-care antimicrobial treatment has been increasing. To address this challenge, a novel antimicrobial magnetic thermotherapy platform has been developed in which a high-amplitude, high-frequency, alternating magnetic field (AMF) is used to rapidly heat magnetic nanoparticles that are bound to Staphylococcus aureus (S. aureus). The antimicrobial efficacy of this platform was evaluated in the treatment of both an in vitro culture model of S. aureus biofilm and a mouse model of cutaneous S. aureus infection. We demonstrated that an antibody-targeted magnetic nanoparticle bound to S. aureus was effective at thermally inactivating S. aureus and achieving accelerated wound healing without causing tissue injury. PMID:23149904

  5. Staphylococcus aureus Induces Release of Bradykinin in Human Plasma

    PubMed Central

    Mattsson, Eva; Herwald, Heiko; Cramer, Henning; Persson, Kristin; Sjöbring, Ulf; Björck, Lars

    2001-01-01

    Staphylococcus aureus is a prominent human pathogen. Here we report that intact S. aureus bacteria activate the contact system in human plasma in vitro, resulting in a massive release of the potent proinflammatory and vasoactive peptide bradykinin. In contrast, no such effect was recorded with Streptococcus pneumoniae. In the activation of the contact system, blood coagulation factor XII and plasma kallikrein play central roles, and a specific inhibitor of these serine proteinases inhibited the release of bradykinin by S. aureus in human plasma. Furthermore, fragments of the cofactor H-kininogen of the contact system efficiently blocked bradykinin release. The results suggest that activation of the contact system at the surface of S. aureus and the subsequent release of bradykinin could contribute to the hypovolemic hypotension seen in patients with severe S. aureus sepsis. The data also suggest that the contact system could be used as a target in the treatment of S. aureus infections. PMID:11349054

  6. Magnetic nanoparticle targeted hyperthermia of cutaneous Staphylococcus aureus infection.

    PubMed

    Kim, Min-Ho; Yamayoshi, Itsukyo; Mathew, Steven; Lin, Hubert; Nayfach, Joseph; Simon, Scott I

    2013-03-01

    The incidence of wound infections that do not adequately respond to standard-of-care antimicrobial treatment has been increasing. To address this challenge, a novel antimicrobial magnetic thermotherapy platform has been developed in which a high-amplitude, high-frequency, alternating magnetic field is used to rapidly heat magnetic nanoparticles that are bound to Staphylococcus aureus (S. aureus). The antimicrobial efficacy of this platform was evaluated in the treatment of both an in vitro culture model of S. aureus biofilm and a mouse model of cutaneous S. aureus infection. We demonstrated that an antibody-targeted magnetic nanoparticle bound to S. aureus was effective at thermally inactivating S. aureus and achieving accelerated wound healing without causing tissue injury. PMID:23149904

  7. High numbers of Staphylococcus aureus at three bathing beaches in South Florida.

    PubMed

    Esiobu, Nwadiuto; Green, Melissa; Echeverry, Andrea; Bonilla, Tonya D; Stinson, Corine Melanie; Hartz, Aaron; Rogerson, Andrew; McCorquodale, Donald S

    2013-01-01

    While the value of Staphylococcus aureus as an indicator for non-enteric diseases is unclear, understanding its prevalence in recreational beaches would prove useful, given its pathogenic potential. Staphylococcus aureus levels were evaluated in sand and seawater at three beaches during one year. To elucidate possible S. aureus sources or colonization trends, distribution in sand was analyzed at Hollywood Beach. Staphylococcus aureus levels fluctuated throughout the study with highest average densities detected in dry sand (3.46 × 10⁵ CFU/g, Hobie Beach), particularly at beaches with high human density. Patchy distribution marked hotspots of human use and/or possible bacterial re-growth. Data from a brief epidemiological survey indicated a very slight association between beach usage and skin conditions; suggesting high S. aureus levels in sand may not necessarily constitute major health risks. Because the possibility of disease transmission exists, particularly to children and immuno-compromised beach-goers, periodic surveying of highly frequented beaches seems warranted. PMID:22924435

  8. Variation among Staphylococcus aureus membrane vesicle proteomes affects cytotoxicity of host cells.

    PubMed

    Jeon, Hyejin; Oh, Man Hwan; Jun, So Hyun; Kim, Seung Il; Choi, Chi Won; Kwon, Hyo Il; Na, Seok Hyeon; Kim, Yoo Jeong; Nicholas, Asiimwe; Selasi, Gati Noble; Lee, Je Chul

    2016-04-01

    Staphylococcus aureus secretes membrane-derived vesicles (MVs), which can deliver virulence factors to host cells and induce cytopathology. However, the cytopathology of host cells induced by MVs derived from different S. aureus strains has not yet been characterized. In the present study, the cytotoxic activity of MVs from different S. aureus isolates on host cells was compared and the proteomes of S. aureus MVs were analyzed. The MVs purified from S. aureus M060 isolated from a patient with staphylococcal scalded skin syndrome showed higher cytotoxic activity toward host cells than that shown by MVs from three other clinical S. aureus isolates. S. aureus M060 MVs induced HEp-2 cell apoptosis in a dose-dependent manner, but the cytotoxic activity of MVs was completely abolished by treatment with proteinase K. In a proteomic analysis, the MVs from three S. aureus isolates not only carry 25 common proteins, but also carry ≥60 strain-specific proteins. All S. aureus MVs contained δ-hemolysin (Hld), γ-hemolysin, leukocidin D, and exfoliative toxin C, but exfoliative toxin A (ETA) was specifically identified in S. aureus M060 MVs. ETA was delivered to HEp-2 cells via S. aureus MVs. Both rETA and rHld induced cytotoxicity in HEp-2 cells. In conclusion, MVs from clinical S. aureus isolates differ with respect to cytotoxic activity in host cells, and these differences may result from differences in the MV proteomes. Further proteogenomic analysis or mutagenesis of specific genes is necessary to identify cytotoxic factors in S. aureus MVs. PMID:26924795

  9. Stilbenes reduce Staphylococcus aureus hemolysis, biofilm formation, and virulence.

    PubMed

    Lee, Kayeon; Lee, Jin-Hyung; Ryu, Shi Yong; Cho, Moo Hwan; Lee, Jintae

    2014-09-01

    Stilbenoids have a broad range of beneficial health effects. On the other hand, the emergence of antibiotic-resistant Staphylococcus aureus presents a worldwide problem that requires new antibiotics or nonantibiotic strategies. S. aureus produces α-hemolysin (a pore-forming cytotoxin) that has been implicated in the pathogenesis of sepsis and pneumonia. Furthermore, the biofilms formed by S. aureus constitute a mechanism of antimicrobial resistance. In this study, we investigated the hemolytic and antibiofilm activities of 10 stilbene-related compounds against S. aureus. trans-Stilbene and resveratrol at 10 μg/mL were found to markedly inhibit human blood hemolysis by S. aureus, and trans-stilbene also inhibited S. aureus biofilm formation without affecting its bacterial growth. Furthermore, trans-stilbene and resveratrol attenuated S. aureus virulence in vivo in the nematode Caenorhabditis elegans, which is normally killed by S. aureus. Transcriptional analysis showed that trans-stilbene repressed the α-hemolysin hla gene and the intercellular adhesion locus (icaA and icaD) in S. aureus, and this finding was in line with observed reductions in virulence and biofilm formation. In addition, vitisin B, a stilbenoid tetramer, at 1 μg/mL was observed to significantly inhibit human blood hemolysis by S. aureus. PMID:25007234

  10. Staphylococcus aureus: the multi headed hydra resists and controls human complement response in multiple ways.

    PubMed

    Zipfel, Peter F; Skerka, Christine

    2014-03-01

    The Gram positive human pathogen Staphylococcus aureus causes a spectrum of human diseases including pneumonia, tissue and skin infections, endocarditis, pneumonia and sepsis. The increasing number of resistant bacteria and the threat of methicillin resistant S. aureus (MRSA) urge for the need to develop new antibacterial compounds. A prerequisite for development of such anti microbial compounds is a better understanding of the complex immune crosstalk between the pathogenic bacterium and its human host. To this end proteins staphylococcal proteins that contribute to innate immune evasion especially to complement control need to be identified and their mode of action needs to be analyzed in order to provide new targets for immune interference. PMID:24461453

  11. The adherens junctions control susceptibility to Staphylococcus aureus α-toxin

    PubMed Central

    Popov, Lauren M.; Marceau, Caleb D.; Starkl, Philipp M.; Lumb, Jennifer H.; Shah, Jimit; Guerrera, Diego; Cooper, Rachel L.; Merakou, Christina; Bouley, Donna M.; Meng, Wenxiang; Kiyonari, Hiroshi; Takeichi, Masatoshi; Galli, Stephen J.; Bagnoli, Fabio; Citi, Sandra; Carette, Jan E.; Amieva, Manuel R.

    2015-01-01

    Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking among the leading causes of skin and soft tissue infections as well as severe pneumonia. The secreted bacterial α-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for α-toxin cytotoxicity, we conducted a genetic screen using mutagenized haploid human cells. Our screen identified a cytoplasmic member of the adherens junctions, plekstrin-homology domain containing protein 7 (PLEKHA7), as the second most significantly enriched gene after the known α-toxin receptor, a disintegrin and metalloprotease 10 (ADAM10). Here we report a new, unexpected role for PLEKHA7 and several components of cellular adherens junctions in controlling susceptibility to S. aureus α-toxin. We find that despite being injured by α-toxin pore formation, PLEKHA7 knockout cells recover after intoxication. By infecting PLEKHA7−/− mice with methicillin-resistant S. aureus USA300 LAC strain, we demonstrate that this junctional protein controls disease severity in both skin infection and lethal S. aureus pneumonia. Our results suggest that adherens junctions actively control cellular responses to a potent pore-forming bacterial toxin and identify PLEKHA7 as a potential nonessential host target to reduce S. aureus virulence during epithelial infections. PMID:26489655

  12. The adherens junctions control susceptibility to Staphylococcus aureus α-toxin.

    PubMed

    Popov, Lauren M; Marceau, Caleb D; Starkl, Philipp M; Lumb, Jennifer H; Shah, Jimit; Guerrera, Diego; Cooper, Rachel L; Merakou, Christina; Bouley, Donna M; Meng, Wenxiang; Kiyonari, Hiroshi; Takeichi, Masatoshi; Galli, Stephen J; Bagnoli, Fabio; Citi, Sandra; Carette, Jan E; Amieva, Manuel R

    2015-11-17

    Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking among the leading causes of skin and soft tissue infections as well as severe pneumonia. The secreted bacterial α-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for α-toxin cytotoxicity, we conducted a genetic screen using mutagenized haploid human cells. Our screen identified a cytoplasmic member of the adherens junctions, plekstrin-homology domain containing protein 7 (PLEKHA7), as the second most significantly enriched gene after the known α-toxin receptor, a disintegrin and metalloprotease 10 (ADAM10). Here we report a new, unexpected role for PLEKHA7 and several components of cellular adherens junctions in controlling susceptibility to S. aureus α-toxin. We find that despite being injured by α-toxin pore formation, PLEKHA7 knockout cells recover after intoxication. By infecting PLEKHA7(-/-) mice with methicillin-resistant S. aureus USA300 LAC strain, we demonstrate that this junctional protein controls disease severity in both skin infection and lethal S. aureus pneumonia. Our results suggest that adherens junctions actively control cellular responses to a potent pore-forming bacterial toxin and identify PLEKHA7 as a potential nonessential host target to reduce S. aureus virulence during epithelial infections. PMID:26489655

  13. Differential Expression and Roles of Staphylococcus aureus Virulence Determinants during Colonization and Disease

    PubMed Central

    Jenkins, Amy; Diep, Binh An; Mai, Thuy T.; Vo, Nhung H.; Warrener, Paul; Suzich, Joann; Stover, C. Kendall

    2015-01-01

    ABSTRACT Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. PMID:25691592

  14. The Staphylococcus aureus RNome and Its Commitment to Virulence

    PubMed Central

    Felden, Brice; Vandenesch, François; Bouloc, Philippe; Romby, Pascale

    2011-01-01

    Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity. PMID:21423670

  15. Staphylococcus aureus vs. Osteoblast: Relationship and Consequences in Osteomyelitis.

    PubMed

    Josse, Jérôme; Velard, Frédéric; Gangloff, Sophie C

    2015-01-01

    Bone cells, namely osteoblasts and osteoclasts work in concert and are responsible for bone extracellular matrix formation and resorption. This homeostasis is, in part, altered during infections by Staphylococcus aureus through the induction of various responses from the osteoblasts. This includes the over-production of chemokines, cytokines and growth factors, thus suggesting a role for these cells in both innate and adaptive immunity. S. aureus decreases the activity and viability of osteoblasts, by induction of apoptosis-dependent and independent mechanisms. The tight relationship between osteoclasts and osteoblasts is also modulated by S. aureus infection. The present review provides a survey of the relevant literature discussing the important aspects of S. aureus and osteoblast interaction as well as the ability for antimicrobial peptides to kill intra-osteoblastic S. aureus, hence emphasizing the necessity for new anti-infectious therapeutics. PMID:26636047

  16. Staphylococcus aureus vs. Osteoblast: Relationship and Consequences in Osteomyelitis

    PubMed Central

    Josse, Jérôme; Velard, Frédéric; Gangloff, Sophie C.

    2015-01-01

    Bone cells, namely osteoblasts and osteoclasts work in concert and are responsible for bone extracellular matrix formation and resorption. This homeostasis is, in part, altered during infections by Staphylococcus aureus through the induction of various responses from the osteoblasts. This includes the over-production of chemokines, cytokines and growth factors, thus suggesting a role for these cells in both innate and adaptive immunity. S. aureus decreases the activity and viability of osteoblasts, by induction of apoptosis-dependent and independent mechanisms. The tight relationship between osteoclasts and osteoblasts is also modulated by S. aureus infection. The present review provides a survey of the relevant literature discussing the important aspects of S. aureus and osteoblast interaction as well as the ability for antimicrobial peptides to kill intra-osteoblastic S. aureus, hence emphasizing the necessity for new anti-infectious therapeutics. PMID:26636047

  17. Impact of Staphylococcus aureus on Pathogenesis in Polymicrobial Infections

    PubMed Central

    Nair, Nisha; Biswas, Raja; Götz, Friedrich

    2014-01-01

    Polymicrobial infections involving Staphylococcus aureus exhibit enhanced disease severity and morbidity. We reviewed the nature of polymicrobial interactions between S. aureus and other bacterial, fungal, and viral cocolonizers. Microbes that were frequently recovered from the infection site with S. aureus are Haemophilus influenzae, Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus pneumoniae, Corynebacterium sp., Lactobacillus sp., Candida albicans, and influenza virus. Detailed analyses of several in vitro and in vivo observations demonstrate that S. aureus exhibits cooperative relations with C. albicans, E. faecalis, H. influenzae, and influenza virus and competitive relations with P. aeruginosa, Streptococcus pneumoniae, Lactobacillus sp., and Corynebacterium sp. Interactions of both types influence changes in S. aureus that alter its characteristics in terms of colony formation, protein expression, pathogenicity, and antibiotic susceptibility. PMID:24643542

  18. Identification of Infantile Diarrhea Caused by Breast Milk-Transmitted Staphylococcus aureus Infection.

    PubMed

    Chen, Zhong; Pan, Wei-Guang; Xian, Wei-Yi; Cheng, Hang; Zheng, Jin-Xin; Hu, Qing-Hua; Yu, Zhi-Jian; Deng, Qi-Wen

    2016-10-01

    Staphylococcus aureus is a well-known organism which is responsible for a variety of human infectious diseases including skin infections, pneumonia, bacteremia, and endocarditis. Few of the microorganisms can be transmitted from mother to the newborn or infant by milk breastfeeding. This study aims to identify transmission of S. aureus from healthy, lactating mothers to their infants by breastfeeding. Stool specimens of diarrheal infants and breast milk of their mother (totally three pairs) were collected and six Staphylococcus aureus isolates were cultured positively. Homology and molecular characters of isolated strains were tested using pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing. Furthermore, toxin genes detection was also performed. Each pair of isolates has the same PFGE type and spa type. Four Sequence types (STs) were found among all the isolates; they are ST15, ST188, and ST59, respectively. Among the strains, seb, sec, and tst genes were found, and all were negative for pvl gene. The homology of the S. aureus strains isolated from the infants' stool and the mothers' milk was genetically demonstrated, which indicated that breastfeeding may be important in the transmission of S. aureus infection, and the character of S. aureus needed to be further evaluated. PMID:27344596

  19. Superantigens Modulate Bacterial Density during Staphylococcus aureus Nasal Colonization.

    PubMed

    Xu, Stacey X; Kasper, Katherine J; Zeppa, Joseph J; McCormick, John K

    2015-05-01

    Superantigens (SAgs) are potent microbial toxins that function to activate large numbers of T cells in a T cell receptor (TCR) Vβ-specific manner, resulting in excessive immune system activation. Staphylococcus aureus possesses a large repertoire of distinct SAgs, and in the context of host-pathogen interactions, staphylococcal SAg research has focused primarily on the role of these toxins in severe and invasive diseases. However, the contribution of SAgs to colonization by S. aureus remains unclear. We developed a two-week nasal colonization model using SAg-sensitive transgenic mice expressing HLA-DR4, and evaluated the role of SAgs using two well-studied stains of S. aureus. S. aureus Newman produces relatively low levels of staphylococcal enterotoxin A (SEA), and although we did not detect significant TCR-Vβ specific changes during wild-type S. aureus Newman colonization, S. aureus Newman Δsea established transiently higher bacterial loads in the nose. S. aureus COL produces relatively high levels of staphylococcal enterotoxin B (SEB), and colonization with wild-type S. aureus COL resulted in clear Vβ8-specific T cell skewing responses. S. aureus COL Δseb established consistently higher bacterial loads in the nose. These data suggest that staphylococcal SAgs may be involved in regulating bacterial densities during nasal colonization. PMID:26008236

  20. Superantigens Modulate Bacterial Density during Staphylococcus aureus Nasal Colonization

    PubMed Central

    Xu, Stacey X.; Kasper, Katherine J.; Zeppa, Joseph J.; McCormick, John K.

    2015-01-01

    Superantigens (SAgs) are potent microbial toxins that function to activate large numbers of T cells in a T cell receptor (TCR) Vβ-specific manner, resulting in excessive immune system activation. Staphylococcus aureus possesses a large repertoire of distinct SAgs, and in the context of host-pathogen interactions, staphylococcal SAg research has focused primarily on the role of these toxins in severe and invasive diseases. However, the contribution of SAgs to colonization by S. aureus remains unclear. We developed a two-week nasal colonization model using SAg-sensitive transgenic mice expressing HLA-DR4, and evaluated the role of SAgs using two well-studied stains of S. aureus. S. aureus Newman produces relatively low levels of staphylococcal enterotoxin A (SEA), and although we did not detect significant TCR-Vβ specific changes during wild-type S. aureus Newman colonization, S. aureus Newman Δsea established transiently higher bacterial loads in the nose. S. aureus COL produces relatively high levels of staphylococcal enterotoxin B (SEB), and colonization with wild-type S. aureus COL resulted in clear Vβ8-specific T cell skewing responses. S. aureus COL Δseb established consistently higher bacterial loads in the nose. These data suggest that staphylococcal SAgs may be involved in regulating bacterial densities during nasal colonization. PMID:26008236

  1. Oscillating tolerance in synchronized cultures of Staphylococcus aureus.

    PubMed Central

    Holzhoffer, S; Süssmuth, R; Haag, R

    1985-01-01

    Cells of synchronized cultures of Staphylococcus aureus showed an oscillating MBC/MIC ratio when tested with penicillin G. Although the MICs did not differ significantly throughout the cell cycle, the MBC was at its maximum when actively dividing cells were inoculated. PMID:4073867

  2. 21 CFR 866.3700 - Staphylococcus aureus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Staphylococcus aureus serological reagents. 866.3700 Section 866.3700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents §...

  3. 21 CFR 866.3700 - Staphylococcus aureus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Staphylococcus aureus serological reagents. 866.3700 Section 866.3700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents §...

  4. An Interdisciplinary Experiment: Azo-Dye Metabolism by "Staphylococcus Aureus"

    ERIC Educational Resources Information Center

    Brocklesby, Kayleigh; Smith, Robert; Sharp, Duncan

    2012-01-01

    An interdisciplinary and engaging practical is detailed which offers great versatility in the study of a qualitative and quantitative metabolism of azo-dyes by "Staphylococcus aureus". This practical has broad scope for adaptation in the number and depth of variables to allow a focused practical experiment or small research project. Azo-dyes are…

  5. Complete Genome Sequence of Staphylococcus aureus Siphovirus Phage JS01

    PubMed Central

    Jia, Hongying; Bai, Qinqin; Yang, Yongchun

    2013-01-01

    Staphylococcus aureus is the most prevalent and economically significant pathogen causing bovine mastitis. We isolated and characterized one staphylophage from the milk of mastitis-affected cattle and sequenced its genome. Transmission electron microscopy (TEM) observation shows that it belongs to the family Siphovirus. We announce here its complete genome sequence and report major findings from the genomic analysis. PMID:24233583

  6. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells.

    PubMed Central

    Choi, Y W; Kotzin, B; Herron, L; Callahan, J; Marrack, P; Kappler, J

    1989-01-01

    A modification of the polymerase chain reaction has been used to establish the fact that a collection of Staphylococcus aureus toxins are "superantigens," each of which interacts with the T-cell alpha beta receptor of human T cells by means of a specific set of V beta elements. Images PMID:2479030

  7. Vancomycin-resistant Staphylococcus aureus: no apocalypse now.

    PubMed

    Goldstein, F W; Kitzis, M D

    2003-08-01

    The number of reports concerning vancomycin-resistant Staphylococcus aureus is much higher than the number of true resistant strains or unexpected clinical failures. Many confounding factors, including inadequate serum levels, severely ill patients, foreign devices or undrained abscesses, are more likely to be responsible for the clinical failures than resistance to vancomycin. PMID:14616695

  8. Identification of LytSR-regulated genes from Staphylococcus aureus.

    PubMed

    Brunskill, E W; Bayles, K W

    1996-10-01

    In this report, the characterization of a Staphylococcus aureus operon containing two LytSR-regulated genes, lrgA and lrgB, is described. Sequence and mutagenesis studies of these genes suggest that lrgA encodes a murein hydrolase exporter similar to bacteriophage holin proteins while lrgB may encode a protein having murein hydrolase activity. PMID:8824633

  9. Pulsed-field gel electrophoresis typing of Staphylococcus aureus isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pulsed-field gel electrophoresis (PFGE) is the most applied and effective genetic typing method for epidemiological studies and investigation of foodborne outbreaks caused by different pathogens, including Staphylococcus aureus. The technique relies on analysis of large DNA fragments generated by th...

  10. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Staphylococcus Aureus Bacterin-Toxoid. 113.115 Section 113.115 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Inactivated Bacterial Products...

  11. Staphylococcus aureus genomic pattern and atopic dermatitis: may factors other than superantigens be involved?

    PubMed

    Rojo, A; Aguinaga, A; Monecke, S; Yuste, J R; Gastaminza, G; España, A

    2014-04-01

    The purpose of this investigation was to compare the genotypic profiles of Staphylococcus aureus isolated from atopic dermatitis (AD) patients and from control subjects, and to study the relationship between clinical severity, immune response, and genomic pattern of S. aureus isolated from AD patients. We selected 32 patients with AD and S. aureus skin colonization and 31 atopic controls with no history of AD who where asymptomatic carriers of S. aureus. Microarray-based genotyping was performed on S. aureus isolates. In AD patients, clinical severity was assessed using the Scoring Atopic Dermatitis index and total IgE levels and staphylococcal superantigen-specific IgE levels (SEA, SEB, SEC, TSST1) were determined. The genes lukE, lukD, splA, splB, ssl8, and sasG were more frequent in isolates from AD patients. CC30 was more common in isolates from atopic controls than in AD patients. There was a correlation between total IgE and clinical severity, but an association between clinical severity, immune response, and the presence of S. aureus superantigen genes, including enterotoxin genes, could not be demonstrated. Finally, a correlation was found between AD severity and other S. aureus genes, such as sasG and scn. S. aureus factors besides superantigens could be related to the worsening and onset of AD. PMID:24162256

  12. Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria.

    PubMed

    Chen, Changyou; Chen, Linjie; Yi, Yong; Chen, Chuanfang; Wu, Long-Fei; Song, Tao

    2016-01-01

    Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections. PMID:26873320

  13. Early-switch/early-discharge opportunities for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections: proof of concept in the United Arab Emirates

    PubMed Central

    El Houfi, Ashraf; Javed, Nadeem; Solem, Caitlyn T; Macahilig, Cynthia; Stephens, Jennifer M; Raghubir, Nirvana; Chambers, Richard; Li, Jim Z; Haider, Seema

    2015-01-01

    Objectives To describe real-world treatment patterns and health care resource use and to estimate opportunities for early-switch (ES) from intravenous (IV) to oral (PO) antibiotics and early-discharge (ED) for patients hospitalized in the United Arab Emirates (UAE) with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections. Methods This retrospective observational medical chart review study enrolled physicians from four UAE sites to collect data for 24 patients with documented MRSA complicated skin and soft tissue infections, hospitalized between July 2010 and June 2011, and discharged alive by July 2011. Data include clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and PO antibiotic use, and ES and ED eligibility using literature-based and expert-validated criteria. Results Five included patients (20.8%) were switched from IV to PO antibiotics while being inpatients. Actual length of MRSA-active treatment was 10.8±7.0 days, with 9.8±6.6 days of IV therapy. Patients were hospitalized for a mean 13.9±9.3 days. The most frequent initial MRSA-active therapies used were vancomycin (37.5%), linezolid (16.7%), and clindamycin (16.7%). Eight patients were discharged with MRSA-active antibiotics, with linezolid prescribed most frequently (n=3; 37.5%). Fifteen patients (62.5%) met ES criteria and potentially could have discontinued IV therapy 8.3±6.0 days sooner, and eight (33.3%) met ED criteria and potentially could have been discharged 10.9±5.8 days earlier. Conclusion While approximately one-fifth of patients were switched from IV to PO antibiotics in the UAE, there were clear opportunities for further optimization of health care resource use. Over half of UAE patients hospitalized for MRSA complicated skin and soft tissue infections could be eligible for ES, with one-third eligible for ED opportunities, resulting in substantial potential for reductions in IV days and bed days. PMID

  14. Screening for Methicillin-Resistant Staphylococcus aureus Colonization Using Sponges

    PubMed Central

    Lee, Chang-Seop; Montalmont, Bianca; O’Hara, Jessica A.; Syed, Alveena; Chaussard, Charma; McGaha, Traci L.; Pakstis, Diana L.; Lee, Ju-Hyung; Shutt, Kathleen A.; Doi, Yohei

    2015-01-01

    OBJECTIVE Nasal swab culture is the standard method for identifying methicillin-resistant Staphylococcus aureus (MRSA) carriers. However, this method is known to miss a substantial portion of those carrying MRSA elsewhere. We hypothesized that the additional use of a sponge to collect skin culture samples would significantly improve the sensitivity of MRSA detection. DESIGN Hospitalized patients with recent MRSA infection were enrolled and underwent MRSA screening of the forehead, nostrils, pharynx, axilla, and groin with separate swabs and the forehead, axilla, and groin with separate sponges. Staphylococcal cassette chromosome mec (SCCmec) typing was conducted by polymerase chain reaction (PCR). PATIENTS A total of 105 MRSA patients were included in the study. RESULTS At least 1 specimen from 56.2% of the patients grew MRSA. Among patients with at least 1 positive specimen, the detection sensitivities were 79.7% for the swabs and 64.4% for the sponges. Notably, 86.4% were detected by a combination of sponges and nasal swab, and 72.9% were detected by a combination of pharyngeal and nasal swabs, whereas only 50.9% were detected by nasal swab alone (P < 0.0001 and P = 0.0003, respectively). Most isolates had SCCmec type II (59.9%) and IV (35.7%). No correlation was observed between the SCCmec types and collection sites. CONCLUSION Screening using a sponge significantly improves MRSA detection when used in addition to screening with the standard nasal swab. PMID:25627758

  15. Trends of Staphylococcus aureus bloodstream infections in a neonatal intensive care unit from 2000-2009

    PubMed Central

    2014-01-01

    Background Invasive methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections are major causes of numerous neonatal intensive care unit (NICU) outbreaks. There have been increasing reports of MRSA outbreaks in various neonatal intensive care units (NICUs) over the last decade. Our objective was to review the experience of Staphylococcus aureus sepsis in our NICU in the last decade and describe the trends in the incidence of Staphylococcus aureus blood stream infections from 2000 to 2009. Methods A retrospective perinatal database review of all neonates admitted to our NICU with blood cultures positive for Staphylococcus aureus from (Jan 1st 2000 to December 31st 2009) was conducted. Infants were identified from the database and data were collected regarding their clinical characteristics and co-morbidities, including shock with sepsis and mortality. Period A represents patients admitted in 2000-2003. Period B represents patients seen in 2004-2009. Results During the study period, 156/11111 infants were identified with Staphylococcus aureus blood stream infection: 41/4486 (0.91%) infants in Period A and 115/6625 (1.73%) in Period B (p < 0.0004). Mean gestation at birth was 26 weeks for infants in both periods. There were more MRSA infections in Period B (24% vs. 55% p < 0.05) and they were associated with more severe outcomes. In comparing the cases of MRSA infections observed in the two periods, infants in period B notably had significantly more pneumonia cases (2.4% vs. 27%, p = 0.0005) and a significantly higher mortality rate (0% vs. 15.7%, p = 0.0038). The incidences of skin and soft tissue infections and of necrotizing enterocolitis were not significantly changed in the two periods. Conclusion There was an increase in the incidence of Staphylococcus aureus infection among neonates after 2004. Although MSSA continues to be a problem in the NICU, MRSA infections were more prevalent in the

  16. A systematic review and meta-analysis on Staphylococcus aureus carriage in psoriasis, acne and rosacea.

    PubMed

    Totté, J E E; van der Feltz, W T; Bode, L G M; van Belkum, A; van Zuuren, E J; Pasmans, S G M A

    2016-07-01

    Staphylococcus aureus might amplify symptoms in chronic inflammatory skin diseases. This study evaluates skin and mucosal colonization with S. aureus in patients with psoriasis, acne and rosacea. A systematic literature search was conducted. Both odds ratios (OR) for colonization in patients versus controls and the prevalence of colonization in patients are reported. Fifteen articles about psoriasis and 13 about acne (12 having a control group) were included. No study in rosacea met our inclusion criteria. For psoriasis, one study out of three controlled studies showed increased skin colonization (OR 18.86; 95 % confidence interval [CI] 2.20-161.99). Three out of the five studies that reported on nasal colonization showed significant ORs varying from 1.73 (95 % CI 1.16-2.58) to 14.64 (95 % CI 2.82-75.95). For acne one of the three studies that evaluated skin colonization reported a significant OR of 4.16 (95 % CI 1.74-9.94). A relation between nasal colonization and acne was not found. Limitations in study design and low sample sizes should be taken into consideration when interpreting the results. Colonisation with S. aureus seems to be increased in patients with psoriasis. This bacterial species, known for its potential to induce long-lasting inflammation, might be involved in psoriasis pathogenesis. Information on acne is limited. Prospective controlled studies should further investigate the role of S. aureus in chronic inflammatory skin diseases. PMID:27151386

  17. Peptides from Tetraspanin CD9 Are Potent Inhibitors of Staphylococcus Aureus Adherence to Keratinocytes

    PubMed Central

    Ventress, Jennifer K.; Partridge, Lynda J.; Read, Robert C.; Cozens, Daniel; MacNeil, Sheila

    2016-01-01

    Staphylococcus aureus is one of the primary causative agents of skin and wound infections. As bacterial adherence is essential for infection, blocking this step can reduce invasion of host tissues by pathogens. An anti-adhesion therapy, based on a host membrane protein family, the tetraspanins, has been developed that can inhibit the adhesion of S. aureus to human cells. Synthetic peptides derived from a keratinocyte-expressed tetraspanin, CD9, were tested for anti-adhesive properties and at low nanomolar concentrations were shown to inhibit bacterial adhesion to cultured keratinocytes and to be effective in a tissue engineered model of human skin infection. These potential therapeutics had no effect on keratinocyte viability, migration or proliferation, indicating that they could be a valuable addition to current treatments for skin infection. PMID:27467693

  18. Duplex Identification of Staphylococcus aureus by Aptamer and Gold Nanoparticles.

    PubMed

    Chang, Tianjun; Wang, Libo; Zhao, Kexu; Ge, Yu; He, Meng; Li, Gang

    2016-06-01

    Staphylococcus aureus is the top common pathogen causing infections and food poisoning. Identification of S. aureus is crucial for the disease diagnosis and regulation of food hygiene. Herein, we report an aptamer-AuNPs based method for duplex identification of S. aureus. Using AuNPs as an indicator, SA23, an aptamer against S. aureus, can well identify its target from Escherichia coli, Listeria monocytogenes and Pseudomonas aeruginosa. Furthermore, we find citrate-coated AuNPs can strongly bind to S. aureus, but not bind to Salmonella enterica and Proteus mirabilis, which leads to different color changes in salt solution. This colorimetric response is capable of distinguishing S. aureus from S. enteritidis and P. mirabilis. Thus, using the aptasensor and AuNPs together, S. aureus can be accurately identified from the common pathogens. This duplex identification system is a promising platform for simple visual identification of S. aureus. Additionally, in the aptasensing process, bacteria are incubated with aptamers and then be removed before the aptamers adding to AuNPs, which may avoid the interactions between bacteria and AuNPs. This strategy can be potentially applied in principle to detect other cells by AuNPs-based aptasensors. PMID:27427591

  19. Staphylococcus aureus ST121: a globally disseminated hypervirulent clone.

    PubMed

    Rao, Qing; Shang, Weilong; Hu, Xiaomei; Rao, Xiancai

    2015-12-01

    Staphylococcus aureus is a leading cause of bacterial infections in hospitals and communities worldwide. With the development of typing methods, several pandemic clones have been well characterized, including the extensively spreading hospital-associated meticillin-resistant S. aureus (HA-MRSA) clone ST239 and the emerging hypervirulent community-associated (CA) MRSA clone USA300. The multilocus sequence typing method was set up based on seven housekeeping genes; S. aureus groups were defined by the sharing of alleles at ≥ 5 of the seven loci. In many cases, the predicted founder of a group would also be the most prevalent ST within the group. As a predicted founder of major S. aureus groups, approximately 90 % of ST121 strains was meticillin-susceptible S. aureus (MSSA). The majority of ST121 strains carry accessory gene regulator type IV, whereas staphylococcal protein A gene types for ST121 are exceptionally diverse. More than 90 % of S. aureus ST121 strains have Panton-Valentine leukocidin; other enterotoxins, haemolysins, leukocidins and exfoliative toxins also contribute to the high virulence of ST121 strains. Patients suffering from S. aureus ST121 infections often need longer hospitalization and prolonged antimicrobial therapy. In this review, we tried to summarize the epidemiology of the S. aureus clone ST121 and focused on the molecular types, toxin carriage and disease spectrum of this globally disseminated clone. PMID:26445995

  20. Persistent bacteraemia due to methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in a patient with erythrodermic psoriasis.

    PubMed

    Bakri, Faris G; Al-Hommos, Nisreen Abu; Shehabi, Asem; Naffa, Randa G; Cui, Longzhu; Hiramatsu, Keiich

    2007-01-01

    A 49-y-old male with erythrodermic psoriasis developed persistent bacteraemia for 3 months due to methicillin-resistant Staphylococcus aureus despite antimicrobial therapy. The skin was the likely focus. Three consecutive isolates from the blood and 1 from the nose were identical and had vancomycin MIC of 4 mg/l. PMID:17464871

  1. Pharmacokinetics and Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae and Staphylococcus aureus in a Granulocyte-Rich Exudate

    PubMed Central

    Trampuz, Andrej; Laifer, Gerd; Wenk, Markus; Rajacic, Zarko; Zimmerli, Werner

    2002-01-01

    The pharmacokinetics of gatifloxacin were assessed in serum and in skin blister fluid (SBF), as was the pharmacodynamic activity in SBF. Five hours after a single dose of gatifloxacin, SBF killed 2.5 logs of Streptococcus pneumoniae and 1.5 log of Staphylococcus aureus during a 2-h incubation ex vivo. PMID:12384378

  2. Vulvar Abscess Caused by Methicillin-resistant Staphylococcus Aureus (MRSA) in a Postmenopausal Woman

    PubMed Central

    Kim, Tae-Hee; Kim, Soo Ah; Heo, Gyeong-Eun

    2016-01-01

    Infections of the vulva can present a complex differential to the gynecologist, ranging from superficial skin infections to lifethreatening necrotizing fasciitis. Recognition and timely treatment remain universal to skin and soft-tissue infections as the subcutaneous anatomy of the vulva can facilitate rapid spread to other tissues with significant morbidity and mortality. Employing a multidisciplinary team approach to care for vulvar cellulitis and abscess can guide treatment from antibiotic therapies to more aggressive surgical debridement. In this report, we describe a case of vulvar abscess caused by Methicillin-resistant staphylococcus aureus (MRSA) in a postmenopausal woman with underlying diseases of bronchiectasis and atelectasis. PMID:27617247

  3. Systemic loxoscelism in the age of community-acquired methicillin-resistant Staphylococcus aureus.

    PubMed

    Rogers, Karen M; Klotz, Carrie R; Jack, Meg; Seger, Donna

    2011-02-01

    The increase in cases of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), as well as its isolation from the majority of skin and soft tissue abscesses in the emergency department, requires the emergency physician to consider this diagnosis in all skin or soft tissue infections. However, making the diagnosis of MRSA when the wound is actually a cutaneous lesion of a brown recluse spider bite may have untoward consequences. Furthermore, the clinical manifestations of systemic loxoscelism may be misdiagnosed as a systemic staphylococcal infection. We present a patient with systemic loxoscelism who was diagnosed with a systemic infection and received an unnecessary surgical procedure. PMID:20817348

  4. Vulvar Abscess Caused by Methicillin-resistant Staphylococcus Aureus (MRSA) in a Postmenopausal Woman.

    PubMed

    Kim, Tae-Hee; Seap, Bel; Kim, Soo Ah; Heo, Gyeong-Eun

    2016-08-01

    Infections of the vulva can present a complex differential to the gynecologist, ranging from superficial skin infections to lifethreatening necrotizing fasciitis. Recognition and timely treatment remain universal to skin and soft-tissue infections as the subcutaneous anatomy of the vulva can facilitate rapid spread to other tissues with significant morbidity and mortality. Employing a multidisciplinary team approach to care for vulvar cellulitis and abscess can guide treatment from antibiotic therapies to more aggressive surgical debridement. In this report, we describe a case of vulvar abscess caused by Methicillin-resistant staphylococcus aureus (MRSA) in a postmenopausal woman with underlying diseases of bronchiectasis and atelectasis. PMID:27617247

  5. Staphylococcus aureus keratinocyte invasion is mediated by integrin-linked kinase and Rac1.

    PubMed

    Sayedyahossein, Samar; Xu, Stacey X; Rudkouskaya, Alena; McGavin, Martin J; McCormick, John K; Dagnino, Lina

    2015-02-01

    Staphylococcus aureus is a major component of the skin microbiota and causes a large number of serious infections. S. aureus first interacts with epidermal keratinocytes to breach the epidermal barrier through mechanisms not fully understood. By use of primary keratinocytes from mice with epidermis-restricted Ilk gene inactivation and control integrin-linked kinase (ILK)-expressing littermates, we investigated the role of ILK in epidermal S. aureus invasion. Heat-killed, but not live, bacteria were internalized to Rab5- and Rab7-positive phagosomes, and incubation with keratinocyte growth factor increased their uptake 2.5-fold. ILK-deficient mouse keratinocytes internalized bacteria 2- to 4-fold less efficiently than normal cells. The reduced invasion by live S. aureus of ILK-deficient cells was restored in the presence of exogenous, constitutively active Rac1. Thus, Rac1 functions downstream from ILK during invasion. Further, invasion by S. aureus of Rac1-deficient cells was 2.5-fold lower than in normal cells. Paradoxically, staphylococcal cutaneous penetration of mouse skin explants with ILK-deficient epidermis was 35-fold higher than that of normal skin, indicating defects in epidermal barrier function in the absence of ILK. Thus, we identified an ILK-Rac1 pathway essential for bacterial invasion of keratinocytes, and established ILK as a key contributor to prevent invasive staphylococcal cutaneous infection. PMID:25416549

  6. Frequency of methicillin-resistant Staphylococcus aureus nasal colonization among patients suffering from methicillin resistant Staphylococcus aureus bacteraemia

    PubMed Central

    Aslam, Nadia; Izhar, Mateen; Mehdi, Naima

    2013-01-01

    Objective: To determine rate of nasal colonization in Patients suffering from bacteraemia caused by methicillin resistant Staphylococcus aureus. Methods: This descriptive cross sectional study was carried out in a tertiary ca re, University Teaching Hospital (Shaikh Zayed Hospital, Lahore) from October 2010 to August 2011. Nasal swabs were taken from patients suffering from MRSA bacteraemia and were plated on mannitol salt agar plates to isolate Staphylococcus aureus (S. aureus) which were then tested for oxacillin susceptibility. Results: Nasal colonization was present in 52.5% of patients suffering from MRSA bacteraemia. Conclusion: Nasal colonization rates with MRSA were high among patients suffering from MRSA bacteraemia especially in those undergoing dialysis or surgical procedures. Therefore, screening and nasal decolonization should be practiced in hospitals. PMID:24550968

  7. Staphylococcus aureus bacteremia in hemodialysis patients.

    PubMed

    Latos, D L; Stone, W J; Alford, R H

    1977-01-01

    Fifteen male hemodialysis patients developed 21 episodes of S. aureus bacteremia. Infections involving vascular access were responsible for 65% of initial bacteremias. The arteriovenous fistula was the most prevalent type of access used, and thus was responsible for the majority of these illnesses. Phage typing indicated that recurrent episodes were due to reinfection rather than relapse. Complications included endocarditis, osteomyelitis, septic embolism, and pericarditis. One patient died of infectious complications. It is recommended that hemodialysis patients developing bacteremia due to S. aureus receive at least 6 weeks of beta lactamase-resistant antimicrobial therapy. PMID:608860

  8. Evaluation of Staphylococcus aureus Eradication Therapy in Vascular Surgery

    PubMed Central

    Donker, J. M. W.; van Rijen, M. M. L.; Kluytmans, J. A. J. W.; van der Laan, L.

    2016-01-01

    Introduction Surgical site infections (SSI) are a serious complication in vascular surgery which may lead to severe morbidity and mortality. Staphylococcus aureus nasal carriage is associated with increased risk for development of SSIs in central vascular surgery. The risk for SSI can be reduced by perioperative eradication of S. aureus carriage in cardiothoracic and orthopedic surgery. This study analyzes the relation between S. aureus eradication therapy and SSI in a vascular surgery population. Methods A prospective cohort study was performed, including all patients undergoing vascular surgery between February 2013 and April 2015. Patients were screened for S. aureus nasal carriage and, when tested positive, were subsequently treated with eradication therapy. The presence of SSI was recorded based on criteria of the CDC. The control group consisted of a cohort of vascular surgery patients in 2010, who were screened, but received no treatment. Results A total of 444 patients were screened. 104 nasal swabs were positive for S. aureus, these patients were included in the intervention group. 204 patients were screened in the 2010 cohort. 51 tested positive and were included in the control group. The incidence of S. aureus infection was 5 out of 51 (9.8%) in the control group versus 3 out of 104 in the eradication group (2.2%; 95% confidence interval 0.02–1.39; P = 0.13). A subgroup analysis showed that the incidence of S. aureus infection was 3 out of 23 (13.0%) in the control group in central reconstructive surgery versus 0 out of 44 in the intervention group (P = 0.074). The reduction of infection pressure by S. aureus was stronger than the reduction of infection pressure by other pathogens (exact maximum likelihood estimation; OR = 0.0724; 95% CI: 0.001–0.98; p = 0.0475). Conclusion S. aureus eradication therapy reduces the infection pressure of S. aureus, resulting in a reduction of SSIs caused by S. aureus. PMID:27529551

  9. Contribution of Cell Surface Hydrophobicity in the Resistance of Staphylococcus aureus against Antimicrobial Agents.

    PubMed

    Lather, Puja; Mohanty, A K; Jha, Pankaj; Garsa, Anita Kumari

    2016-01-01

    Staphylococcus aureus is found in a wide variety of habitats, including human skin, where many strains are commensals that may be clinically significant or contaminants of food. To determine the physiological characteristics of resistant strain of Staphylococcus aureus against pediocin, a class IIa bacteriocin, a resistant strain was compared with wild type in order to investigate the contribution of hydrophobicity to this resistance. Additional clumping of resistant strain relative to wild type in light microscopy was considered as an elementary evidence of resistance attainment. A delay in log phase attainment was observed in resistant strain compared to the wild type strain. A significant increase in cell surface hydrophobicity was detected for resistant strain in both hexadecane and xylene indicating the contribution of cell surface hydrophobicity as adaptive reaction against antimicrobial agents. PMID:26966577

  10. Contribution of Cell Surface Hydrophobicity in the Resistance of Staphylococcus aureus against Antimicrobial Agents

    PubMed Central

    Lather, Puja; Mohanty, A. K.; Jha, Pankaj; Garsa, Anita Kumari

    2016-01-01

    Staphylococcus aureus is found in a wide variety of habitats, including human skin, where many strains are commensals that may be clinically significant or contaminants of food. To determine the physiological characteristics of resistant strain of Staphylococcus aureus against pediocin, a class IIa bacteriocin, a resistant strain was compared with wild type in order to investigate the contribution of hydrophobicity to this resistance. Additional clumping of resistant strain relative to wild type in light microscopy was considered as an elementary evidence of resistance attainment. A delay in log phase attainment was observed in resistant strain compared to the wild type strain. A significant increase in cell surface hydrophobicity was detected for resistant strain in both hexadecane and xylene indicating the contribution of cell surface hydrophobicity as adaptive reaction against antimicrobial agents. PMID:26966577

  11. Isolation of Staphylococcus aureus from sputum in cystic fibrosis.

    PubMed

    Sparham, P D; Lobban, D I; Speller, D C

    1978-10-01

    The success in the isolation of Staphylococcus aureus of different methods of sputum processing was investigated in 60 specimens collected from 14 patients with cystic fibrosis during a seven-month period. Fifty specimens (83%) from 11 patients yielded Staph. aureus by one or more methods. Direct plating of purulent portions of sputum on to media designed for general use in respiratory infections gave unsatisfactory results (35% yield of Staph. aureus). Some increase in isolations was obtained with preliminary liquefaction of sputum; but the best results were given by the addition of a medium selective for staphylococci (mannitol salt agar, BBL) or by initial sonication of sputum (each 83% yield). Seven of the 11 strains of Staph. aureus were thymidine-dependent and otherwise atypical in laboratory characteristics; these were isolated from patients who had received co-trimoxazole. PMID:101553

  12. Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice.

    PubMed

    Yang, Yilong; Qian, Mengying; Yi, Shaoqiong; Liu, Shuling; Li, Bing; Yu, Rui; Guo, Qiang; Zhang, Xiaopeng; Yu, Changming; Li, Jianmin; Xu, Junjie; Chen, Wei

    2016-01-01

    Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections. PMID:26926145

  13. Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice

    PubMed Central

    Yang, Yilong; Qian, Mengying; Yi, Shaoqiong; Liu, Shuling; Li, Bing; Yu, Rui; Guo, Qiang; Zhang, Xiaopeng; Yu, Changming; Li, Jianmin; Xu, Junjie; Chen, Wei

    2016-01-01

    Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections. PMID:26926145

  14. Staphylococcus aureus with reduced susceptibility to vancomycin in healthcare settings.

    PubMed

    Spagnolo, A M; Orlando, P; Panatto, D; Amicizia, D; Perdelli, F; Cristina, M L

    2014-12-01

    Glycopeptide resistance in Staphylococcus aureus is a source of great concern because, especially in hospitals, this class of antibiotics, particularly vancomycin, is one of the main resources for combating infections caused by methicillin-resistant Staphylococcus aureus strains (MRSA). Reduced susceptibility to vancomycin (VISA) was first described in 1996 in Japan; since then, a phenotype with heterogeneous resistance to vancomycin (h-VISA) has emerged. H-VISA isolates are characterised by the presence of a resistant subpopulation, typically at a rate of 1 in 10(5) organisms, which constitutes the intermediate stage betweenfully vancomycin-susceptible S. aureus (VSSA) and VISA isolates. As VISA phenotypes are almost uniformly cross-resistant to teicoplanin, they are also called Glycopeptides-intermediate Staphylococcus aureus strains (GISA) and, in the case of heterogeneous resistance to glycopeptides, h-GISA. The overall prevalence of h-VISA is low, accounting for approximately 1.3% of all MRSA isolates tested. Mortality due to h-GISA infections is very high (about 70%), especially among patients hospitalised in high-risk departments, such as intensive care units (ICU). Given the great clinical relevance of strains that are heteroresistant to glycopeptides and the possible negative impact on treatment choices, it is important to draw up and implement infection control practices, including surveillance, the appropriate use of isolation precautions, staff training, hand hygiene, environmental cleansing and good antibiotic stewardship. PMID:26137787

  15. Glycolytic Dependency of High-Level Nitric Oxide Resistance and Virulence in Staphylococcus aureus

    PubMed Central

    Vitko, Nicholas P.; Spahich, Nicole A.

    2015-01-01

    ABSTRACT Staphylococcus aureus is a prolific human pathogen capable of causing severe invasive disease with a myriad of presentations. The ability of S. aureus to cause infection is strongly linked with its capacity to overcome the effects of innate immunity, whether by directly killing immune cells or expressing factors that diminish the impact of immune effectors. One such scenario is the induction of lactic acid fermentation by S. aureus in response to host nitric oxide (NO·). This fermentative activity allows S. aureus to balance redox during NO·-induced respiration inhibition. However, little is known about the metabolic substrates and pathways that support this activity. Here, we identify glycolytic hexose catabolism as being essential for S. aureus growth in the presence of high levels of NO·. We determine that glycolysis supports S. aureus NO· resistance by allowing for ATP and precursor metabolite production in a redox-balanced and respiration-independent manner. We further demonstrate that glycolysis is required for NO· resistance during phagocytosis and that increased levels of extracellular glucose limit the effectiveness of phagocytic killing by enhancing NO· resistance. Finally, we demonstrate that S. aureus glycolysis is essential for virulence in both sepsis and skin/soft tissue models of infection in a time frame consistent with the induction of innate immunity and host NO· production. PMID:25852157

  16. Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus.

    PubMed

    Lee, Jin-Hyung; Cho, Hyun Seob; Kim, Younghoon; Kim, Jung-Ae; Banskota, Suhrid; Cho, Moo Hwan; Lee, Jintae

    2013-05-01

    Human pathogens can readily develop drug resistance due to the long-term use of antibiotics that mostly inhibit bacterial growth. Unlike antibiotics, antivirulence compounds diminish bacterial virulence without affecting cell viability and thus, may not lead to drug resistance. Staphylococcus aureus is a major agent of nosocomial infections and produces diverse virulence factors, such as the yellow carotenoid staphyloxanthin, which promotes resistance to reactive oxygen species (ROS) and the host immune system. To identify novel antivirulence compounds, bacterial signal indole present in animal gut and diverse indole derivatives were investigated with respect to reducing staphyloxanthin production and the hemolytic activity of S. aureus. Treatment with indole or its derivative 7-benzyloxyindole (7BOI) caused S. aureus to become colorless and inhibited its hemolytic ability without affecting bacterial growth. As a result, S. aureus was more easily killed by hydrogen peroxide (H₂O₂) and by human whole blood in the presence of indole or 7BOI. In addition, 7BOI attenuated S. aureus virulence in an in vivo model of nematode Caenorhabditis elegans, which is readily infected and killed by S. aureus. Transcriptional analyses showed that both indole and 7BOI repressed the expressions of several virulence genes such as α-hemolysin gene hla, enterotoxin seb, and the protease genes splA and sspA and modulated the expressions of the important regulatory genes agrA and sarA. These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection. PMID:23318836

  17. Brain microabscesses in a porcine model of Staphylococcus aureus sepsis

    PubMed Central

    2013-01-01

    Background Sepsis caused by Staphylococcus aureus often leads to brain microabscesses in humans. Animal models of haematogenous brain abscesses would be useful to study this condition in detail. Recently, we developed a model of S. aureus sepsis in pigs and here we report that brain microabscesses develop in pigs with such induced S. aureus sepsis. Twelve pigs were divided into three groups. Nine pigs received an intravenous inoculation of S. aureus once at time 0 h (group 1) or twice at time 0 h and 12 h (groups 2 and 3). In each group the fourth pig served as control. The pigs were euthanized at time 12 h (Group 1), 24 h (Group 2) and 48 h (Group 3) after the first inoculation. The brains were collected and examined histopathologically. Results All inoculated pigs developed sepsis and seven out of nine pigs developed brain microabscesses. The microabscesses contained S. aureus and were located in the prosencephalon and mesencephalon. Chorioditis and meningitis occurred from 12 h after inoculation. Conclusions Pigs with experimental S. aureus sepsis often develop brain microabscesses. The porcine brain pathology mirrors the findings in human sepsis patients. We therefore suggest the pig as a useful animal model of the development of brain microabscesses caused by S. aureus sepsis. PMID:24176029

  18. Global antibody response to Staphylococcus aureus live-cell vaccination.

    PubMed

    Selle, Martina; Hertlein, Tobias; Oesterreich, Babett; Klemm, Theresa; Kloppot, Peggy; Müller, Elke; Ehricht, Ralf; Stentzel, Sebastian; Bröker, Barbara M; Engelmann, Susanne; Ohlsen, Knut

    2016-01-01

    The pathogen Staphylococcus aureus causes a broad range of severe diseases and is feared for its ability to rapidly develop resistance to antibiotic substances. The increasing number of highly resistant S. aureus infections has accelerated the search for alternative treatment options to close the widening gap in anti-S. aureus therapy. This study analyses the humoral immune response to vaccination of Balb/c mice with sublethal doses of live S. aureus. The elicited antibody pattern in the sera of intravenously and intramuscularly vaccinated mice was determined using of a recently developed protein array. We observed a specific antibody response against a broad set of S. aureus antigens which was stronger following i.v. than i.m. vaccination. Intravenous but not intramuscular vaccination protected mice against an intramuscular challenge infection with a high bacterial dose. Vaccine protection was correlated with the strength of the anti-S. aureus antibody response. This study identified novel vaccine candidates by using protein microarrays as an effective tool and showed that successful vaccination against S. aureus relies on the optimal route of administration. PMID:27103319

  19. Global antibody response to Staphylococcus aureus live-cell vaccination

    PubMed Central

    Selle, Martina; Hertlein, Tobias; Oesterreich, Babett; Klemm, Theresa; Kloppot, Peggy; Müller, Elke; Ehricht, Ralf; Stentzel, Sebastian; Bröker, Barbara M.; Engelmann, Susanne; Ohlsen, Knut

    2016-01-01

    The pathogen Staphylococcus aureus causes a broad range of severe diseases and is feared for its ability to rapidly develop resistance to antibiotic substances. The increasing number of highly resistant S. aureus infections has accelerated the search for alternative treatment options to close the widening gap in anti-S. aureus therapy. This study analyses the humoral immune response to vaccination of Balb/c mice with sublethal doses of live S. aureus. The elicited antibody pattern in the sera of intravenously and intramuscularly vaccinated mice was determined using of a recently developed protein array. We observed a specific antibody response against a broad set of S. aureus antigens which was stronger following i.v. than i.m. vaccination. Intravenous but not intramuscular vaccination protected mice against an intramuscular challenge infection with a high bacterial dose. Vaccine protection was correlated with the strength of the anti-S. aureus antibody response. This study identified novel vaccine candidates by using protein microarrays as an effective tool and showed that successful vaccination against S. aureus relies on the optimal route of administration. PMID:27103319

  20. Management of healthcare-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Hsu, Li-Yang; Wijaya, Limin; Tan, Ban-Hock

    2005-12-01

    Healthcare-associated methicillin-resistant Staphylococcus aureus is a major cause of nosocomial infections worldwide, with significant attributable morbidity and mortality in addition to pronounced healthcare costs. Treatment results with vancomycin--the current recommended antibiotic for serious methicillin-resistant S. aureus infections--have not been impressive. The recent availability of effective antimicrobial agents other than glycopeptides, such as linezolid and daptomycin, as well as the anticipated approval of newer agents with diverse mechanisms of action, has somewhat ameliorated the threat posed by this organism. However, these drugs are expensive, and there is still no overall satisfactory strategy for reducing the incidence of healthcare-associated methicillin-resistant S. aureus in endemic regions. Although early results with the Society for Healthcare Epidemiology of America guidelines give cause for cautious optimism, long-term experience is lacking, and it is likely that these guidelines will have to be adapted according to local conditions and resources before implementation. Trends to keep in mind when considering the problem of healthcare-associated methicillin-resistant S. aureus include the advent of community-associated methicillin-resistant S. aureus, and the propensity of S. aureus to evolve and acquire resistance determinants over time. This was last vividly demonstrated by the handful of vancomycin-resistant S. aureus isolated recently, which had acquired the vancomycin resistance gene from vancomycin-resistant enterococci. PMID:16307502

  1. Molecular Correlates of Host Specialization in Staphylococcus aureus

    PubMed Central

    Herron-Olson, Lisa; Fitzgerald, J. Ross; Musser, James M.; Kapur, Vivek

    2007-01-01

    Background The majority of Staphylococcus aureus isolates that are recovered from either serious infections in humans or from mastitis in cattle represent genetically distinct sets of clonal groups. Moreover, population genetic analyses have provided strong evidence of host specialization among S. aureus clonal groups associated with human and ruminant infection. However, the molecular basis of host specialization in S. aureus is not understood. Methodology/Principal Findings We sequenced the genome of strain ET3-1, a representative isolate of a common bovine mastitis-causing S. aureus clone. Strain ET3-1 encodes several genomic elements that have not been previously identified in S. aureus, including homologs of virulence factors from other Gram-positive pathogens. Relative to the other sequenced S. aureus associated with human infection, allelic variation in ET3-1 was high among virulence and surface-associated genes involved in host colonization, toxin production, iron metabolism, antibiotic resistance, and gene regulation. Interestingly, a number of well-characterized S. aureus virulence factors, including protein A and clumping factor A, exist as pseudogenes in ET3-1. Whole-genome DNA microarray hybridization revealed considerable similarity in the gene content of highly successful S. aureus clones associated with bovine mastitis, but not among those clones that are only infrequently recovered from bovine hosts. Conclusions/Significance Whole genome sequencing and comparative genomic analyses revealed a set of molecular genetic features that distinguish clones of highly successful bovine-associated S. aureus optimized for mastitis pathogenesis in cattle from those that infect human hosts or are only infrequently recovered from bovine sources. Further, the results suggest that modern bovine specialist clones diverged from a common ancestor resembling human-associated S. aureus clones through a combination of foreign DNA acquisition and gene decay. PMID:17971880

  2. Differential responses of osteoblasts and macrophages upon Staphylococcus aureus infection

    PubMed Central

    2014-01-01

    Background Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization. Results We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and a significantly higher (100 fold) level of live intracellular S. aureus was detected in macrophages compared to osteoblasts. However, the percentage of S. aureus survival after infection was significantly lower in macrophages compared to osteoblasts at post-infection days 1–6. Interestingly, macrophages had relatively lower viability in shorter infection time periods (i.e. 0.5-4 h; significant at 2 h) but higher viability in longer infection time periods (i.e. 6–8 h; significant at 8 h) compared to osteoblasts. In addition, S. aureus infection led to significant changes in reactive oxygen species production in both macrophages and osteoblasts. Moreover, infected osteoblasts had significantly lower alkaline phosphatase activity at post-infection day 7 and infected macrophages had higher phagocytosis activity compared to non-infected cells. Conclusions S. aureus was found to internalize and survive within osteoblasts and macrophages and led to differential responses between osteoblasts and macrophages. These findings may assist in evaluation of the pathogenesis of chronic and recurrent infections which may be related to the intracellular persistence of bacteria within host cells. PMID:25059520

  3. Role of Protein A in Nonspecific Immunofluorescence of Staphylococcus aureus

    PubMed Central

    Forsgren, Arne; Forsum, Urban

    1970-01-01

    γG-globulin from nonimmunized rabbits and from rabbits immunized with various bacteria reacted in the immunofluorescence technique with protein A-containing Staphylococcus aureus. Pepsin digestion of most immunoglobulin preparations eliminated the reaction, thus showing that the Fc fragment is involved and that the reaction is not a true antigen-antibody reaction. As the specific immunological activity of the immunoglobulin molecules was intact after digestion, it is suggested that the method be used to eliminate reactions with S. aureus in the fluorescent-antibody technique. PMID:16557850

  4. Methicillin-resistant Staphylococcus aureus colonization in schoolteachers in Ontario.

    PubMed

    Hanselman, Beth A; Kruth, Steven A; Rousseau, Joyce; Weese, J Scott

    2008-11-01

    A prospective study of methicillin-resistant Staphylococcus aureus (MRSA) colonization was performed involving teachers at a science teachers' conference in Toronto, Ontario. Nasal swabs and questionnaire data were collected from consenting individuals. MRSA colonization was identified in seven of 220 (3.2%) participants. No colonized individuals reported recent contact with the health care system, antimicrobial therapy, residence with health care workers or previous MRSA infections. Methicillin-susceptible S aureus colonization was identified in 72 of 220 (33%) individuals. The prevalence of MRSA colonization was higher than expected for a purportedly low-risk population. PMID:19436569

  5. Methicillin-resistant Staphylococcus aureus colonization in schoolteachers in Ontario

    PubMed Central

    Hanselman, Beth A; Kruth, Steven A; Rousseau, Joyce; Weese, J Scott

    2008-01-01

    A prospective study of methicillin-resistant Staphylococcus aureus (MRSA) colonization was performed involving teachers at a science teachers’ conference in Toronto, Ontario. Nasal swabs and questionnaire data were collected from consenting individuals. MRSA colonization was identified in seven of 220 (3.2%) participants. No colonized individuals reported recent contact with the health care system, antimicrobial therapy, residence with health care workers or previous MRSA infections. Methicillin-susceptible S aureus colonization was identified in 72 of 220 (33%) individuals. The prevalence of MRSA colonization was higher than expected for a purportedly low-risk population. PMID:19436569

  6. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat.

    PubMed

    Grundmann, Hajo; Aires-de-Sousa, Marta; Boyce, John; Tiemersma, Edine

    2006-09-01

    Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people. Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition. Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials--the beta-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems. PMID:16950365

  7. Evaluation of Two New Chromogenic Media, CHROMagar MRSA and S. aureus ID, for Identifying Staphylococcus aureus and Screening Methicillin-Resistant S. aureus

    PubMed Central

    Hedin, Göran; Fang, Hong

    2005-01-01

    Thirty-nine methicillin-resistant Staphylococcus aureus (MRSA) isolates with diverse genetic backgrounds and two reference strains were correctly identified as S. aureus on CHROMagar MRSA and S. aureus ID media. Growth inhibition on CHROMagar MRSA was noted. A combination of cefoxitin disk and S. aureus ID was found suitable for rapid MRSA screening. PMID:16081989

  8. Comparative In Vitro Activities of Oritavancin, Dalbavancin, and Vancomycin against Methicillin-Resistant Staphylococcus aureus Isolates in a Nondividing State.

    PubMed

    Belley, Adam; Lalonde Seguin, David; Arhin, Francis; Moeck, Greg

    2016-07-01

    Antibacterial agents that kill nondividing bacteria may be of utility in treating persistent infections. Oritavancin and dalbavancin are bactericidal lipoglycopeptides that are approved for acute bacterial skin and skin structure infections in adults caused by susceptible Gram-positive pathogens. Using time-kill methodology, we demonstrate that oritavancin exerts bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) isolates that are maintained in a nondividing state in vitro, whereas dalbavancin and the glycopeptide vancomycin do not. PMID:27067327

  9. Efficacy of teat dips containing a hypochlorous acid germicide against experimental challenge with Staphylococcus aureus and Streptococcus agalactiae.

    PubMed

    Boddie, R L; Nickerson, S C

    1996-09-01

    Two teat dip formulations containing sodium dichloroisocyanurate, which released hypochlorous acid (2800 ppm) as the active ingredient, were tested for efficacy against new Staphylococcus aureus and Streptococcus agalactiae IMI using an experimental challenge model. Product 1 reduced the number of new Staph. aureus IMI by 73.6% and reduced the number of new Strep. agalactiae IMI by 65.1%. Product 2 reduced the number of new Staph. aureus IMI by 69.0% and reduced the number of new Strep. agalactiae IMI by 63.5%. No adverse effects on teat skin condition were observed over the course of the studies. PMID:8899537

  10. Genomics of Staphylococcus

    NASA Astrophysics Data System (ADS)

    Lindsay, Jodi A.

    The staphylococci are Gram-positive cocci that divide to form clusters that look like grapes. By 16S ribosomal sequencing, they are most closely related to the Gram-positive, low G+C content Bacillus-Lactobacillus-Staphylococcus genera (Woese, 1987). There are over 30 species of staphylococci identified, and they are typically found on the skin and mucous membranes of mammals. About a dozen species are frequently carried on humans, including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus capitis, Staphylococcus hominis, Staphylococcus cohnii, Staphylococcus lugdunensis, Staphylococcus schleiferi, Staphylococcus saprophyticus, Staphylococcus simulans, Staphylococcus warneri and Staphylococcus xylosus.

  11. A double outbreak of exfoliative toxin-producing strains of Staphylococcus aureus in a maternity unit.

    PubMed

    Dave, J; Reith, S; Nash, J Q; Marples, R R; Dulake, C

    1994-02-01

    This report describes a double outbreak of staphylococcal scalded skin syndrome (SSSS) in which two distinct tetracycline-resistant strains of Staphylococcus aureus producing different exfoliative toxins were involved. In the first phase the daytime staff of the delivery unit and eczematous skin conditions in midwives were implicated as the probable source. In the second phase a source within a post-natal ward was suggested with local cross-infection. In the final phase both sources were epidemiologically linked to cases of SSSS. Because early discharge was the policy of the unit many cases presented in the community rather than in the hospital. Confirmation of epidemiological findings was provided by additional laboratory studies. Two distinct strains of S. aureus could be defined, differing in phage-typing patterns, the exfoliative toxin produced, plasmid profile, cadmium resistance and bacteriocin production. Strict care in hand washing with a chlorhexidine-containing detergent was an important control measure. PMID:8119349

  12. Determination of aminoglycoside resistance in Staphylococcus aureus by DNA hybridization.

    PubMed Central

    Dickgiesser, N; Kreiswirth, B N

    1986-01-01

    A method is described for identification of the genes conferring aminoglycoside resistance in Staphylococcus aureus by dot-blot and Southern blot techniques. As radioactive probes, fragments of plasmids pAT48, pUBH2, and pH13, carrying the genes for an aminocyclitol-3'-phosphotransferase, an aminocyclitol-4'-adenylyltransferase, and an aminocyclitol-2''-phosphotransferase-aminocyclitol-6'-acetyltransferase, respectively, were used. Images PMID:3729351

  13. Methicillin-resistant Staphylococcus aureus in HIV-infected patients

    PubMed Central

    Hidron, Alicia I; Kempker, Russell; Moanna, Abeer; Rimland, David

    2010-01-01

    Concordant with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting, colonization and infections with this pathogen have become a prevalent problem among the human immunodeficiency virus (HIV)-positive population. A variety of different host- and, possibly, pathogen-related factors may play a role in explaining the increased prevalence and incidence observed. In this article, we review pathophysiology, epidemiology, clinical manifestations, and treatment of MRSA in the HIV-infected population. PMID:21694896

  14. Impacts of enterotoxin gene cluster-encoded superantigens on local and systemic experimental Staphylococcus aureus infections.

    PubMed

    Nowrouzian, F L; Ali, A; Badiou, C; Dauwalder, O; Lina, G; Josefsson, E

    2015-07-01

    Staphylococcus aureus is both a component of the normal skin flora and an important pathogen. It expresses a range of recognized and putative virulence factors, such as enterotoxins with superantigenic properties. Several superantigen genes, i.e., seg, sei, selm, seln, and selo, are encoded by the enterotoxin gene cluster (egc), which is found in the majority of S. aureus isolates. Carriage of egc is associated with fitness of S. aureus in the gut microbiota, but it is not known if it contributes to pathogenicity. We constructed egc+ (functional for the seg, selm, and selo genes) and isogenic egc- S. aureus mutants, and investigated their virulence profiles in murine infection models. No effect of egc was seen in a local skin and soft tissue infection model, but in an invasive infection model, increased weight loss was observed after infection with the egc+ as compared to the egc- mutant. Mortality and arthritis were not affected by egc status. Our data suggest that egc has limited effects on the virulence of S. aureus. It may primarily function as a colonization factor increasing commensal fitness, although it might have some aggravating effects on the infection when the bacteria reach the blood. PMID:25864191

  15. Sterilization Efficiency of a Novel Electrochemical Disinfectant against Staphylococcus aureus.

    PubMed

    Zhang, Qian; Ma, Ruonan; Tian, Ying; Su, Bo; Wang, Kaile; Yu, Shuang; Zhang, Jue; Fang, Jing

    2016-03-15

    Disinfection of hazardous microorganisms that may challenge environmental safety is a crucial issue for economic and public health. Here, we explore the potential of a novel electrochemical disinfectant named plasma activated water (PAW), which was generated by nonthermal plasma, for inactivating Staphylococcus aureus (S. aureus). Meanwhile, the influence of bovine serum albumin (BSA) on the PAW disinfection efficacy was investigated. In the presence of BSA, PAW treatments achieved a reduction of S. aureus ranging from 2.1 to 5.5 Log, when without BSA it reached 7 Log. The sterilization efficacy depended on the PAW treatment time of S. aureus and plasma activation time for PAW generation. The results of electron spin resonance spectra showed the concentrations of hydroxyl radical (OH•) and nitric oxide radical (NO•) in water activated by plasma for 10 min (10-PAW) were higher than those in water activated by plasma for 5 min (5-PAW). Additionally, the physiological analysis of S. aureus demonstrated that the integrity of cell membrane, membrane potential, and intracellular pH homeostasis as well as DNA structure were damaged by PAW, and the molecule structure and chemical bonds of S. aureus were also altered due to PAW. Thus, PAW can be a promising chemical-free and environmentally friendly electrochemical disinfectant for application in the medical and food industries. PMID:26857097

  16. Staphylococcus aureus – antimicrobial resistance and the immunocompromised child

    PubMed Central

    McNeil, J Chase

    2014-01-01

    Children with immunocompromising conditions represent a unique group for the acquisition of antimicrobial resistant infections due to their frequent encounters with the health care system, need for empiric antimicrobials, and immune dysfunction. These infections are further complicated in that there is a relative paucity of literature on the clinical features and management of Staphylococcus aureus infections in immunocompromised children. The available literature on the clinical features, antimicrobial susceptibility, and management of S. aureus infections in immunocompromised children is reviewed. S. aureus infections in children with human immunodeficiency virus (HIV) are associated with higher HIV viral loads and a greater degree of CD4 T-cell suppression. In addition, staphylococcal infections in children with HIV often exhibit a multidrug resistant phenotype. Children with cancer have a high rate of S. aureus bacteremia and associated complications. Increased tolerance to antiseptics among staphylococcal isolates from pediatric oncology patients is an emerging area of research. The incidence of S. aureus infections among pediatric solid organ transplant recipients varies considerably by the organ transplanted; in general however, staphylococci figure prominently among infections in the early posttransplant period. Staphylococcal infections are also prominent pathogens among children with a number of immunodeficiencies, notably chronic granulomatous disease. Significant gaps in knowledge exist regarding the epidemiology and management of S. aureus infection in these vulnerable children. PMID:24855381

  17. Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus pseudintermedius isolated from various animals.

    PubMed

    Rubin, Joseph E; Ball, Katherine R; Chirino-Trejo, Manuel

    2011-02-01

    This study characterized the antimicrobial susceptibility of 221 Staphylococcus aureus isolated from various species, and 60 canine Staphylococcus pseudintermedius isolated from 1986 through 2000 at the Western College of Veterinary Medicine (WCVM). Resistance of S. aureus was most common to penicillin (31%) and tetracycline (14%); resistance of S. pseudintermedius to penicillin was present in 8% and to tetracycline in 34% of isolates. Resistance to trimethoprim/sulfamethoxazole was only seen among S. pseudintermedius, and there was no resistance to amoxicillin/clavulanate, ampicillin/sulbactam, cephalothin, amikacin, gentamicin, enrofloxacin, chloramphenicol, or rifampin among any isolate. Inducible clindamycin resistance was found in both S. aureus and S. pseudintermedius, highlighting the need for careful interpretation of culture and susceptibility test results. There were significant differences in the minimum inhibitory concentrations of penicillin, ciprofloxacin, enrofloxacin, clindamycin, erythromycin, chloramphenicol, and tetracycline between avian, bovine, equine, and porcine isolates. PMID:21532820

  18. Anaerobic Conditions Induce Expression of Polysaccharide Intercellular Adhesin in Staphylococcus aureus and Staphylococcus epidermidis

    PubMed Central

    Cramton, Sarah E.; Ulrich, Martina; Götz, Friedrich; Döring, Gerd

    2001-01-01

    Products of the intercellular adhesion (ica) operon in Staphylococcus aureus and Staphylococcus epidermidis synthesize a linear β-1,6-linked glucosaminylglycan. This extracellular polysaccharide mediates bacterial cell-cell adhesion and is required for biofilm formation, which is thought to increase the virulence of both pathogens in association with prosthetic biomedical implants. The environmental signal(s) that triggers ica gene product and polysaccharide expression is unknown. Here we demonstrate that anaerobic in vitro growth conditions lead to increased polysaccharide expression in both S. aureus and S. epidermidis, although the regulation is less stringent in S. epidermidis. Anaerobiosis also dramatically stimulates ica-specific mRNA expression in ica- and polysaccharide-positive strains of both S. aureus and S. epidermidis. These data suggest a mechanism whereby ica gene expression and polysaccharide production may act as a virulence factor in an anaerobic environment in vivo. PMID:11349079

  19. Sphingoid bases are taken up by Escherichia coli and Staphylococcus aureus and induce ultrastructural damage

    PubMed Central

    Fischer, Carol L.; Walters, Katherine S.; Drake, David R.; Blanchette, Derek R.; Dawson, Deborah V.; Brogden, Kim A.; Wertz, Philip W.

    2013-01-01

    Sphingoid bases found in the outer layers of the skin exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria. We investigated the uptake of several sphingoid bases by Escherichia coli and Staphylococcus aureus, and assessed subsequent ultrastructural damage. E. coli and S. aureus were incubated with D-sphingosine, dihydrosphingosine, or phytosphingosine at ten times their MIC for 0.5 h and 4 h, respectively, to kill 50% of viable bacteria. Treated bacterial cells were immediately prepared for SEM, TEM, and analyzed for lipid content by QTLC. E. coli and S. aureus treated with sphingoid bases were distorted and their surfaces were concave and rugate. Significant differences were observed in the visual surface area relative to controls for both E. coli and S. aureus when treated with dihydrosphingosine and sphingosine (p<0.0001) but not phytosphingosine. While sphingoid base-treated S. aureus exhibited disruption and loss of cell wall and membrane, E. coli cytoplasmic membranes appeared intact and the outer envelope uncompromised. Both E. coli and S. aureus cells contained unique internal inclusion bodies, likely associated with cell death. QTLC demonstrated extensive uptake of sphingoid bases by the bacteria. Hence, sphingoid bases induce both extracellular and intracellular damage and cause intracellular inclusions that may reflect lipid uptake. PMID:23128426

  20. In Vivo Activity of a Novel Polymeric Guanidine in Experimental Skin Infection with Methicillin-Resistant Staphylococcus aureus▿

    PubMed Central

    Kratzer, Christina; Tobudic, Selma; Macfelda, Karin; Graninger, Wolfgang; Georgopoulos, Apostolos

    2007-01-01

    The in vivo efficacy of the novel polymeric guanidine AKACID Plus was evaluated in a guinea pig model of experimental skin infection with methicillin-resistant Staphylococcus aureus (MRSA). Topical application of AKACID Plus at concentrations of ≥0.5% was as effective as mupirocin 2% cream in the treatment of superficial skin infection with MRSA. PMID:17620381

  1. Repurposing the Antihistamine Terfenadine for Antimicrobial Activity against Staphylococcus aureus

    PubMed Central

    2015-01-01

    Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure–activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied through this round of optimization; however, given the overall improvement in activity of the set, terfenadine-based analogues provide a novel structural class of antimicrobial compounds with potential for further characterization as part of the continuing process to meet the current need for new antibiotics. PMID:25238555

  2. Population Structure of Staphylococcus aureus from Trinidad & Tobago

    PubMed Central

    Monecke, Stefan; Stieber, Bettina; Roberts, Rashida; Akpaka, Patrick Eberechi; Slickers, Peter; Ehricht, Ralf

    2014-01-01

    It has been shown previously that high rates of methicillin- and mupirocin-resistant Staphylococcus aureus exist in the Caribbean islands of Trinidad and Tobago, as well as a high prevalence of Panton-Valentine leukocidin-positive S. aureus. Beyond these studies, limited typing data have been published. In order to obtain insight into the population structure not only of MRSA but also of methicillin-susceptible S. aureus, 294 clinical isolates collected in 2012/2013 were typed by microarray hybridisation. A total of 15.31% of the tested isolates were MRSA and 50.00% were PVL-positive. The most common MSSA strains were PVL-positive CC8-MSSA (20.41% of all isolates tested), PVL-positive CC152-MSSA (9.52%) and PVL-positive CC30-MSSA (8.84%) while the most common MRSA were ST239-MRSA-III&SCCmer (9.18%) and ST8-MRSA-IV, “USA300” (5.78%). 2.38% of characterised isolates belonged to distinct strains likely to be related to “Staphylococcus argenteus” lineages. The population structure of S. aureus isolates suggests an importation of strains from Africa, endemicity of PVL-positive MSSA (mainly CC8) and of ST239-MRSA-III, and a recent emergence of the PVL-positive CC8-MRSA-IV strain “USA300”. PMID:24586536

  3. Vitamin A deficiency predisposes to Staphylococcus aureus infection.

    PubMed Central

    Wiedermann, U; Tarkowski, A; Bremell, T; Hanson, L A; Kahu, H; Dahlgren, U I

    1996-01-01

    We have investigated the consequences of vitamin A deficiency in a rat model of T-cell-dependent and superantigen-mediated Staphylococcus aureus arthritis. After intravenous inoculation of enterotoxin A-producing staphylococci, the vitamin-A-deficient rats showed a decreased weight gain compared with the paired fed controls despite equal food consumption. The control rats developed arthritis in the first few days after bacterial inoculation, with a peak frequency at day 5, and then gradually recovered; however, the frequency of arthritis 18 days after bacterial inoculation was 86% among the vitamin A-deficient rats and 44% among the control rats. During this period, 3 of 10 deficient rats and 1 of 10 control rats died. Further in vitro analysis revealed that T-cell responses to S. aureus were significantly higher in the vitamin A-deficient rats than in the control animals. In contrast, B-cell reactivity, measured as immunoglobulin levels, autoantibody levels, and specific antibacterial antibody levels in serum, did not differ between the groups. Interestingly, the innate host defense mechanisms against S. aureus were also profoundly affected by vitamin A deficiency. Thus, despite a larger number of circulating phagocytic cells in the vitamin-A-deficient group, the capacity to phagocytize and exert intracellular killing of S. aureus was significantly decreased in comparison with the control rats. Furthermore, serum from the vitamin A-deficient rats inoculated with Staphylococcus aureus displayed decreased complement lysis activity. Our results suggest that the increased susceptibility to S. aureus infection observed in the vitamin-A-deficient rats is due to a concerted action of antigen-specific T-cell hyperactivity, impaired function of the phagocytes, and decreased complement activity. PMID:8557341

  4. Bovine Staphylococcus aureus: Subtyping, evolution, and zoonotic transfer.

    PubMed

    Boss, R; Cosandey, A; Luini, M; Artursson, K; Bardiau, M; Breitenwieser, F; Hehenberger, E; Lam, Th; Mansfeld, M; Michel, A; Mösslacher, G; Naskova, J; Nelson, S; Podpečan, O; Raemy, A; Ryan, E; Salat, O; Zangerl, P; Steiner, A; Graber, H U

    2016-01-01

    Staphylococcus aureus is globally one of the most important pathogens causing contagious mastitis in cattle. Previous studies using ribosomal spacer (RS)-PCR, however, demonstrated in Swiss cows that Staph. aureus isolated from bovine intramammary infections are genetically heterogeneous, with Staph. aureus genotype B (GTB) and GTC being the most prominent genotypes. Furthermore, Staph. aureus GTB was found to be contagious, whereas Staph. aureus GTC and all the remaining genotypes were involved in individual cow disease. In addition to RS-PCR, other methods for subtyping Staph. aureus are known, including spa typing and multilocus sequence typing (MLST). They are based on sequencing the spa and various housekeeping genes, respectively. The aim of the present study was to compare the 3 analytic methods using 456 strains of Staph. aureus isolated from milk of bovine intramammary infections and bulk tanks obtained from 12 European countries. Furthermore, the phylogeny of animal Staph. aureus was inferred and the zoonotic transfer of Staph. aureus between cattle and humans was studied. The analyzed strains could be grouped into 6 genotypic clusters, with CLB, CLC, and CLR being the most prominent ones. Comparing the 3 subtyping methods, RS-PCR showed the highest resolution, followed by spa typing and MLST. We found associations among the methods but in many cases they were unsatisfactory except for CLB and CLC. Cluster CLB was positive for clonal complex (CC)8 in 99% of the cases and typically positive for t2953; it is the cattle-adapted form of CC8. Cluster CLC was always positive for tbl 2645 and typically positive for CC705. For CLR and the remaining subtypes, links among the 3 methods were generally poor. Bovine Staph. aureus is highly clonal and a few clones predominate. Animal Staph. aureus always evolve from human strains, such that every human strain may be the ancestor of a novel animal-adapted strain. The zoonotic transfer of IMI- and milk-associated strains

  5. A rare case of acute epiglottitis due to Staphylococcus aureus in an adult

    PubMed Central

    Harris, Clare; Sharkey, Lisa; Koshy, George; Simler, Nicola; Karas, Johannis Andreas

    2012-01-01

    Epiglottitis has been mainly associated with childhood infection with Haemophilis influenzae type B but cases of adult epiglottitis are increasing. We report here a case of adult epiglottitis and present evidence that it was caused by Staphylococcus aureus. A 48-year old patient with clinical symptoms of epiglottitis grew Staphylococcus aureus in pure culture from an epiglottal swab. Staphylococcus aureus should be considered as a potential pathogen in adult epiglottitis. PMID:24470933

  6. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice

    PubMed Central

    Cho, John S.; Pietras, Eric M.; Garcia, Nairy C.; Ramos, Romela Irene; Farzam, David M.; Monroe, Holly R.; Magorien, Julie E.; Blauvelt, Andrew; Kolls, Jay K.; Cheung, Ambrose L.; Cheng, Genhong; Modlin, Robert L.; Miller, Lloyd S.

    2010-01-01

    Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in γδ but not αβ T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vγ5+ γδ T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R–deficient mice had a phenotype similar to that of γδ T cell–deficient mice. Importantly, γδ T cell–deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17–producing epidermal γδ T cells in innate immunity against S. aureus cutaneous infection. PMID:20364087

  7. Methicillin-resistant Staphylococcus aureus: an overview for manual therapists☆

    PubMed Central

    Green, Bart N.; Johnson, Claire D.; Egan, Jonathon Todd; Rosenthal, Michael; Griffith, Erin A.; Evans, Marion Willard

    2012-01-01

    Objective Methicillin-resistant Staphylococcus aureus (MRSA) is associated with difficult-to-treat infections and high levels of morbidity. Manual practitioners work in environments where MRSA is a common acquired infection. The purpose of this review is to provide a practical overview of MRSA as it applies to the manual therapy professions (eg, physical and occupational therapy, athletic training, chiropractic, osteopathy, massage, sports medicine) and to discuss how to identify and prevent MRSA infections in manual therapy work environments. Methods PubMed and CINAHL were searched from the beginning of their respective indexing years through June 2011 using the search terms MRSA, methicillin-resistant Staphylococcus aureus, and Staphylococcus aureus. Texts and authoritative Web sites were also reviewed. Pertinent articles from the authors' libraries were included if they were not already identified in the literature search. Articles were included if they were applicable to ambulatory health care environments in which manual therapists work or if the content of the article related to the clinical management of MRSA. Results Following information extraction, 95 citations were included in this review, to include 76 peer-reviewed journal articles, 16 government Web sites, and 3 textbooks. Information was organized into 10 clinically relevant categories for presentation. Information was organized into the following clinically relevant categories: microbiology, development of MRSA, risk factors for infection, clinical presentation, diagnostic tests, screening tests, reporting, treatment, prevention for patients and athletes, and prevention for health care workers. Conclusion Methicillin-resistant S aureus is a health risk in the community and to patients and athletes treated by manual therapists. Manual practitioners can play an essential role in recognizing MRSA infections and helping to control its transmission in the health care environment and the community

  8. Lactobacillus reuteri protects epidermal keratinocytes from Staphylococcus aureus-induced cell death by competitive exclusion.

    PubMed

    Prince, Tessa; McBain, Andrew J; O'Neill, Catherine A

    2012-08-01

    Recent studies have suggested that the topical application of probiotic bacteria can improve skin health or combat disease. We have utilized a primary human keratinocyte culture model to investigate whether probiotic bacteria can inhibit Staphylococcus aureus infection. Evaluation of the candidate probiotics Lactobacillus reuteri ATCC 55730, Lactobacillus rhamnosus AC413, and Lactobacillus salivarius UCC118 demonstrated that both L. reuteri and L. rhamnosus, but not L. salivarius, reduced S. aureus-induced keratinocyte cell death in both undifferentiated and differentiated keratinocytes. Keratinocyte survival was significantly higher if the probiotic was applied prior to (P < 0.01) or simultaneously with (P < 0.01) infection with S. aureus but not when added after infection had commenced (P > 0.05). The protective effect of L. reuteri was not dependent on the elaboration of inhibitory substances such as lactic acid. L. reuteri inhibited adherence of S. aureus to keratinocytes by competitive exclusion (P = 0.026). L. salivarius UCC118, however, did not inhibit S. aureus from adhering to keratinocytes (P > 0.05) and did not protect keratinocyte viability. S. aureus utilizes the α5β1 integrin to adhere to keratinocytes, and blocking of this integrin resulted in a protective effect similar to that observed with probiotics (P = 0.03). This suggests that the protective mechanism for L. reuteri-mediated protection of keratinocytes was by competitive exclusion of the pathogen from its binding sites on the cells. Our results suggest that use of a topical probiotic prophylactically could inhibit the colonization of skin by S. aureus and thus aid in the prevention of infection. PMID:22582077

  9. Lactobacillus reuteri Protects Epidermal Keratinocytes from Staphylococcus aureus-Induced Cell Death by Competitive Exclusion

    PubMed Central

    Prince, Tessa; McBain, Andrew J.

    2012-01-01

    Recent studies have suggested that the topical application of probiotic bacteria can improve skin health or combat disease. We have utilized a primary human keratinocyte culture model to investigate whether probiotic bacteria can inhibit Staphylococcus aureus infection. Evaluation of the candidate probiotics Lactobacillus reuteri ATCC 55730, Lactobacillus rhamnosus AC413, and Lactobacillus salivarius UCC118 demonstrated that both L. reuteri and L. rhamnosus, but not L. salivarius, reduced S. aureus-induced keratinocyte cell death in both undifferentiated and differentiated keratinocytes. Keratinocyte survival was significantly higher if the probiotic was applied prior to (P < 0.01) or simultaneously with (P < 0.01) infection with S. aureus but not when added after infection had commenced (P > 0.05). The protective effect of L. reuteri was not dependent on the elaboration of inhibitory substances such as lactic acid. L. reuteri inhibited adherence of S. aureus to keratinocytes by competitive exclusion (P = 0.026). L. salivarius UCC118, however, did not inhibit S. aureus from adhering to keratinocytes (P > 0.05) and did not protect keratinocyte viability. S. aureus utilizes the α5β1 integrin to adhere to keratinocytes, and blocking of this integrin resulted in a protective effect similar to that observed with probiotics (P = 0.03). This suggests that the protective mechanism for L. reuteri-mediated protection of keratinocytes was by competitive exclusion of the pathogen from its binding sites on the cells. Our results suggest that use of a topical probiotic prophylactically could inhibit the colonization of skin by S. aureus and thus aid in the prevention of infection. PMID:22582077

  10. Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence

    PubMed Central

    Yoong, Pauline; Torres, Victor J.

    2015-01-01

    Staphylococcus aureus subverts host defences by producing a collection of virulence factors including bi-component pore-forming leukotoxins. Despite extensive sequence conservation, each leukotoxin has unique properties, including disparate cellular receptors and species specificities. How these toxins collectively influence S. aureus pathogenesis is unknown. Here we demonstrate that the leukotoxins LukSF-PV and LukED antagonize each other's cytolytic activities on leukocytes and erythrocytes by forming inactive hybrid complexes. Remarkably, LukSF-PV inhibition of LukED haemolytic activity on both human and murine erythrocytes prevents the release of nutrients required for in vitro bacterial growth. Using in vivo murine models of infection, we show that LukSF-PV negatively influences S. aureus virulence and colonization by inhibiting LukED. Thus, while S. aureus leukotoxins can certainly injure immune cells, the discovery of leukotoxin antagonism suggests that they may also play a role in reducing S. aureus virulence and maintaining infection without killing the host. PMID:26330208

  11. A systematic review of animal models for Staphylococcus aureus osteomyelitis

    PubMed Central

    Reizner, W.; Hunter, J.G.; O’Malley, N.T.; Southgate, R.D.; Schwarz, E.M.; Kates, S.L.

    2015-01-01

    Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed & Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorized by animal species and are further classified by the setting of the infection. Study methods are summarized and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model’s strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting. PMID:24668594

  12. Superantigen profiling of Staphylococcus aureus infective endocarditis isolates.

    PubMed

    Chung, Jin-Won; Karau, Melissa J; Greenwood-Quaintance, Kerryl E; Ballard, Alessandro D; Tilahun, Ashenafi; Khaleghi, Shahryar Rostamkolaei; David, Chella S; Patel, Robin; Rajagopalan, Govindarajan

    2014-06-01

    The frequency of superantigen production among Staphylococcus aureus isolates associated with endocarditis is not well defined. We tested 154 S. aureus isolates from definite infective endocarditis cases for the presence of staphylococcal enterotoxins A-E, H, and TSST-1 by PCR, enzyme-linked immunosorbent assay, and using an HLA-DR3 transgenic mouse splenocyte proliferation assay. Sixty-three isolates (50.8%) tested positive for at least 1 superantigen gene, with 21 (16.9%) testing positive for more than 2. tst (28.6%) was most common, followed by seb (27%), sea (22.2%), sed (20.6%), see (17.5%), and sec (11.1%). Of 41 methicillin-resistant S. aureus, 21 had superantigen genes, with sed being more frequently detected in this group compared to methicillin-susceptible S. aureus (P < 0.05). Superantigen genes were not associated with mortality (P = 0.81). 75% of PCR-positive isolates induced robust splenocyte proliferation. Overall, more than half of S. aureus isolates causing endocarditis carry superantigen genes, of which most are functional. PMID:24745820

  13. Methicillin-resistant Staphylococcus aureus in central Iowa wildlife.

    PubMed

    Wardyn, Shylo E; Kauffman, Lin K; Smith, Tara C

    2012-10-01

    Livestock and pets have been identified as carriers of Staphylococcus aureus; however, the role of wild animals as a reservoir of S. aureus strains has not yet been examined. We conducted a pilot study to determine the prevalence of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in 37 species of wild animals rehabilitated at a university clinic. Nasal, wing, wound, and cloacal swabs were collected. Of 114 animals, seven (6.1%) were MSSA-positive and three (2.6%) were MRSA-positive. The MRSA isolates were obtained from two eastern cottontail rabbits (Sylvilagus floridanus) and a Lesser Yellowlegs (Tringa flavipes), a migratory shorebird. Antibiotic resistance testing of the MRSA isolates revealed that two were additionally resistant to tetracycline and erythromycin, and the third isolate was also resistant to erythromycin, clindamycin, and levofloxacin. All three isolates were positive for the Panton-Valentine leukocidin (PVL) gene. Sequence typing of the staphylococcal protein A (spa) region revealed one MRSA isolate to be t002, whereas the other two MRSA isolates were found to be t008. Our results suggest that S. aureus, including MRSA, is being carried by wild animals, although at a low prevalence with the limited number of animals tested. Additional studies are needed to determine how this may impact human health. PMID:23060511

  14. The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus

    PubMed Central

    Alonzo, Francis

    2014-01-01

    SUMMARY The ability to produce water-soluble proteins with the capacity to oligomerize and form pores within cellular lipid bilayers is a trait conserved among nearly all forms of life, including humans, single-celled eukaryotes, and numerous bacterial species. In bacteria, some of the most notable pore-forming molecules are protein toxins that interact with mammalian cell membranes to promote lysis, deliver effectors, and modulate cellular homeostasis. Of the bacterial species capable of producing pore-forming toxic molecules, the Gram-positive pathogen Staphylococcus aureus is one of the most notorious. S. aureus can produce seven different pore-forming protein toxins, all of which are believed to play a unique role in promoting the ability of the organism to cause disease in humans and other mammals. The most diverse of these pore-forming toxins, in terms of both functional activity and global representation within S. aureus clinical isolates, are the bicomponent leucocidins. From the first description of their activity on host immune cells over 100 years ago to the detailed investigations of their biochemical function today, the leucocidins remain at the forefront of S. aureus pathogenesis research initiatives. Study of their mode of action is of immediate interest in the realm of therapeutic agent design as well as for studies of bacterial pathogenesis. This review provides an updated perspective on our understanding of the S. aureus leucocidins and their function, specificity, and potential as therapeutic targets. PMID:24847020

  15. Involvement of Iron in Biofilm Formation by Staphylococcus aureus

    PubMed Central

    Huang, Hsiu-Yun; Cheng, Yi-Ching

    2012-01-01

    Staphylococcus aureus is a human pathogen that forms biofilm on catheters and medical implants. The authors' earlier study established that 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) inhibits biofilm formation by S. aureus by preventing the initial attachment of the cells to a solid surface and reducing the production of polysaccharide intercellular adhesin (PIA). Our cDNA microarray and MALDI-TOF mass spectrometric studies demonstrate that PGG treatment causes the expression of genes and proteins that are normally expressed under iron-limiting conditions. A chemical assay using ferrozine verifies that PGG is a strong iron chelator that depletes iron from the culture medium. This study finds that adding FeSO4 to a medium that contains PGG restores the biofilm formation and the production of PIA by S. aureus SA113. The requirement of iron for biofilm formation by S. aureus SA113 can also be verified using a semi-defined medium, BM, that contains an iron chelating agent, 2, 2′-dipyridyl (2-DP). Similar to the effect of PGG, the addition of 2-DP to BM medium inhibits biofilm formation and adding FeSO4 to BM medium that contains 2-DP restores biofilm formation. This study reveals an important mechanism of biofilm formation by S. aureus SA113. PMID:22479621

  16. Enterotoxin gene profiles among Staphylococcus aureus isolated from raw milk

    PubMed Central

    Nazari, R; Godarzi, H; Rahimi Baghi, F; Moeinrad, M

    2014-01-01

    Milk is considered a nutritious food because it contains several important nutrients including proteins and vitamins. Conversely, it can be a vehicle for several pathogenic bacteria such as Staphylococcus aureus. This study aimed to analyze the frequency of genes encoding the nine Staphylococcal enterotoxins (SEs) and enterotoxin gene profiles in S. aureus isolates derived from raw bovine milk. A total of 52 S. aureus isolates were obtained from 246 milk samples of 246 dairy cows from eight different farms in Qom, Iran. On the basis of cultural and biochemical properties as well as by amplification of the 23S rRNA specific to S. aureus, all isolates could be identified as S. aureus. Of the 52 isolates studied, 80.7% were positive for one or more genes encoding the enterotoxins, and 12 different genotypes were identified. The gene encoding for enterotoxin A (Sea) was the most frequent (16 isolates, 30.7%), followed by Seb (14 isolates, 26.9%) and Sed (8 isolates, 15.37%). Among the genes encoding the other enterotoxins, Seg and Seh were the most frequently observed (8 isolates each, 15.38%), followed by Sej (6 isolates, 11.5%) and Sei (1 isolates, 3.84%). With the recent identification of new SEs, the frequency of enterotoxigenic strains has increased, suggesting that the pathogenic potential of Staphylococci may be higher than previously thought. These results of enterotoxin genes positivity of milk-derived Staphylococci constitute a potential risk for consumers’ health. PMID:27175141

  17. Crystal Violet and XTT Assays on Staphylococcus aureus Biofilm Quantification.

    PubMed

    Xu, Zhenbo; Liang, Yanrui; Lin, Shiqi; Chen, Dingqiang; Li, Bing; Li, Lin; Deng, Yang

    2016-10-01

    Staphylococcus aureus (S. Aureus) is a common food-borne pathogenic microorganism. Biofilm formation remains the major obstruction for bacterial elimination. The study aims at providing a basis for determining S. aureus biofilm formation. 257 clinical samples of S. aureus isolates were identified by routine analysis and multiplex PCR detection and found to contain 227 MRSA, 16 MSSA, 11 MRCNS, and 3 MSCNS strains. Two assays for quantification of S. aureus biofilm formation, the crystal violet (CV) assay and the XTT (tetrazolium salt reduction) assay, were optimized, evaluated, and further compared. In CV assay, most isolates formed weak biofilm 74.3 %), while the rest formed moderate biofilm (23.3 %) or strong biofilm (2.3 %). However, most isolates in XTT assay showed weak metabolic activity (77.0 %), while the rest showed moderate metabolic activity (17.9 %) or high metabolic activity (5.1 %). In this study, we found a distinct strain-to-strain dissimilarity in terms of both biomass formation and metabolic activity, and it was concluded from this study that two assays were mutual complementation rather than being comparison. PMID:27324342

  18. Prevalence of Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus in Retail Ready-to-Eat Foods in China.

    PubMed

    Yang, Xiaojuan; Zhang, Jumei; Yu, Shubo; Wu, Qingping; Guo, Weipeng; Huang, Jiahui; Cai, Shuzhen

    2016-01-01

    Staphylococcus aureus, particularly methicillin-resistant S.aureus (MRSA), is a life-threatening pathogen in humans, and its presence in food is a public health concern. MRSA has been identified in foods in China, but little information is available regarding MRSA in ready-to-eat (RTE) foods. We aimed to investigate the prevalence of S. aureus and MRSA in Chinese retail RTE foods. All isolated S. aureus were tested for antimicrobial susceptibility, and MRSA isolates were further characterized by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. Of the 550 RTE foods collected from 2011 to 2014, 69 (12.5%) were positive for S. aureus. Contamination levels were mostly in the range of 0.3-10 most probable number (MPN)/g, with five samples exceeding 10 MPN/g. Of the 69 S. aureus isolates, seven were identified as MRSA by cefoxitin disc diffusion test. Six isolates were mecA-positive, while no mecC-positive isolates were identified. In total, 75.8% (47/62) of the methicillin-susceptible S. aureus isolates and all of the MRSA isolates were resistant to three or more antibiotics. Amongst the MRSA isolates, four were identified as community-acquired strains (ST59-MRSA-IVa (n = 2), ST338-MRSA-V, ST1-MRSA-V), while one was a livestock-associated strain (ST9, harboring an unreported SCCmec type 2C2). One novel sequence type was identified (ST3239), the SCCmec gene of which could not be typed. Overall, our findings showed that Chinese retail RTE foods are likely vehicles for transmission of multidrug-resistant S. aureus and MRSA lineages. This is a serious public health risk and highlights the need to implement good hygiene practices. PMID:27375562

  19. Prevalence of Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus in Retail Ready-to-Eat Foods in China

    PubMed Central

    Yang, Xiaojuan; Zhang, Jumei; Yu, Shubo; Wu, Qingping; Guo, Weipeng; Huang, Jiahui; Cai, Shuzhen

    2016-01-01

    Staphylococcus aureus, particularly methicillin-resistant S.aureus (MRSA), is a life-threatening pathogen in humans, and its presence in food is a public health concern. MRSA has been identified in foods in China, but little information is available regarding MRSA in ready-to-eat (RTE) foods. We aimed to investigate the prevalence of S. aureus and MRSA in Chinese retail RTE foods. All isolated S. aureus were tested for antimicrobial susceptibility, and MRSA isolates were further characterized by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. Of the 550 RTE foods collected from 2011 to 2014, 69 (12.5%) were positive for S. aureus. Contamination levels were mostly in the range of 0.3–10 most probable number (MPN)/g, with five samples exceeding 10 MPN/g. Of the 69 S. aureus isolates, seven were identified as MRSA by cefoxitin disc diffusion test. Six isolates were mecA-positive, while no mecC-positive isolates were identified. In total, 75.8% (47/62) of the methicillin-susceptible S. aureus isolates and all of the MRSA isolates were resistant to three or more antibiotics. Amongst the MRSA isolates, four were identified as community-acquired strains (ST59-MRSA-IVa (n = 2), ST338-MRSA-V, ST1-MRSA-V), while one was a livestock-associated strain (ST9, harboring an unreported SCCmec type 2C2). One novel sequence type was identified (ST3239), the SCCmec gene of which could not be typed. Overall, our findings showed that Chinese retail RTE foods are likely vehicles for transmission of multidrug-resistant S. aureus and MRSA lineages. This is a serious public health risk and highlights the need to implement good hygiene practices. PMID:27375562

  20. Ecthyma-gangrenosum-like lesions associated with methicillin-resistant Staphylococcus aureus infection.

    PubMed

    Sen, Hüseyin; Inangil, Gökhan; Sahin, Levent; Dere, Kamer; Ozkan, Sezai; Dağli, Güner

    2009-07-01

    Ecthyma gangrenosum (EG) manifests as a skin lesion and is commonly associated with Pseudomonas aeruginosa septicemia in immunocompromised patients. Other viral, fungal and bacterial agents can also cause EG. The first clinical observation is grouped vesicles with surrounding erythema. Within a few days, they evolve into a gangrenous ulcer with a black/gray eschar surrounded by an erythematous halo. Herein, we present a patient with chronic obstructive pulmonary disease who developed EG-like lesions due to methicillin-resistant Staphylococcus aureus infection while he was in the intensive care unit. PMID:19027336

  1. Evaluation of Antimicrobial Resistance in Staphylococcus aureus Isolates by Years

    PubMed Central

    Rağbetli, Cennet; Parlak, Mehmet; Bayram, Yasemin; Guducuoglu, Huseyin; Ceylan, Nesrin

    2016-01-01

    Objective. Recently, community and hospital-acquired infections with Staphylococcus aureus have increased and raised antibiotic resistant isolates. In this study, we aimed to evaluate the antibiotic resistance profile of S. aureus isolates over several years in various clinical specimens from our hospital. Materials and Methods. S. aureus strains from 2009 to 2014 were isolated from various clinical samples at Yuzuncu Yil University, Dursun Odabas Medical Center, Microbiology Laboratory, and their antibiotic susceptibility test results were retrospectively investigated. The isolates were identified by conventional methods, and antibiotic susceptibility tests were performed by the Phoenix (Becton Dickinson, USA) automated system method according to Clinical and Laboratory Standards Institute (CLSI) standards. Results. A total of 1,116 S. aureus isolates were produced and methicillin-resistant S. aureus (MRSA) to 21% of all S. aureus isolates between 2009 and 2014. According to the results of susceptibility tests of all isolates of S. aureus, they have been identified as sensitive to vancomycin, daptomycin, linezolid, and levofloxacin. While the resistance rates to nitrofurantoin, quinupristin-dalfopristin, and trimethoprim-sulfamethoxazole were determined as 0.3%, 2.4%, and 6%, respectively, resistance rates to penicillin, erythromycin, rifampicin, gentamicin, and clindamycin were determined as 100%, 18%, 14%, 14%, and 11%, respectively. The highest percentage of methicillin resistance was determined as 30% in 2009, and the resistance was determined to have decreased in subsequent years (20%, 16%, 13%, 19%, and 21%) (p < 0.001). Conclusion. Currently, retrospective evaluations of causes of nosocomial infection should be done periodically. We think that any alteration of resistance over the years has to be identified, and all centers must determine their own resistance profiles, in order to guide empirical therapies. Reducing the rate of antibiotic resistance will

  2. Characterization of Staphylococcus aureus Biofilm Formation in Urinary Tract Infection

    PubMed Central

    YOUSEFI, Masoud; POURMAND, Mohammad Reza; FALLAH, Fatemeh; HASHEMI, Ali; MASHHADI, Rahil; NAZARI-ALAM, Ali

    2016-01-01

    Background: The aim of this study was to investigate the antibiotic susceptibility pattern as well as the phenotypic and genotypic biofilm formation ability of Staphylococcus aureus isolates from patients with urinary tract infection (UTI). Methods: A total of 39 isolates of S. aureus were collected from patients with UTI. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disk-diffusion. We used the Modified Congo red agar (MCRA) and Microtiter plate methods to assess the ability of biofilm formation. All isolates were examined for determination of biofilm related genes, icaA, fnbA, clfA and bap using PCR method. Results: Linezolid, quinupristin/dalfopristin and chloramphenicol were the most effective agents against S. aureus isolates. Overall, 69.2% of S. aureus isolates were biofilm producers. Resistance to four antibiotics such as nitrofurantoin (71.4% vs. 28.6%, P=0.001), tetracycline (57.7% vs. 42.3%, P=0.028), erythromycin and ciprofloxacin (56% vs. 44%, P=0.017) was higher among biofilm producers than non-biofilm producers. The icaA, fnbA and clfA genes were present in all S. aureus isolates. However, bap gene was not detected in any of the isolates. Conclusion: Our findings reinforce the role of biofilm formation in resistance to antimicrobial agents. Trimethoprimsulfamethoxazole and doxycycline may be used as an effective treatment for UTI caused by biofilm producers S. aureus. Our results suggest that biofilm formation is not dependent to just icaA, fnbA, clfA and bap genes harbor in S. aureus strains. PMID:27252918

  3. Staphylococcus aureus small colony variants in diabetic foot infections.

    PubMed

    Cervantes-García, Estrella; García-Gonzalez, Rafael; Reyes-Torres, Angélica; Resendiz-Albor, Aldo Arturo; Salazar-Schettino, Paz María

    2015-01-01

    Background : Staphylococcus aureus (S. aureus) is one of the major pathogens causing chronic infections. The ability of S. aureus to acquire resistance to a diverse range of antimicrobial compounds results in limited treatment options, particularly in methicillin-resistant S. aureus (MRSA). A mechanism by which S. aureus develops reduced susceptibility to antimicrobials is through the formation of small colony variants (SCVs). Infections by SCVs of S. aureus are an upcoming problem due to difficulties in laboratory diagnosis and resistance to antimicrobial therapy. Methods : A prospective study was performed on 120 patients diagnosed with both type 2 diabetes mellitus and infected diabetic foot ulcers. The study was carried out from July 2012 to December 2013 in Hospital General de Mexico. The samples were cultured in blood agar, mannitol salt agar, and MacConkey agar media, and incubated at 37°C in aerobic conditions. Results : We describe the first known cases of diabetic foot infections caused by MRSA-SCVs in patients diagnosed with type 2 diabetes mellitus and infected diabetic foot ulcers. In all of our cases, the patients had not received any form of gentamicin therapy. Conclusions : The antibiotic therapy commonly used in diabetic patients with infected diabetic foot ulcers fails in the case of MRSA-SCVs because the intracellular location protects S. aureus-SCVs from the host's defenses and also helps them resist antibiotics. The cases studied in this article add to the spectrum of persistent and relapsing infections attributed to MRSA-SCVs and emphasizes that these variants may also play a relevant role in diabetic foot infections. PMID:25787018

  4. Staphylococcus aureus small colony variants in diabetic foot infections

    PubMed Central

    Cervantes-García, Estrella; García-Gonzalez, Rafael; Reyes-Torres, Angélica; Resendiz-Albor, Aldo Arturo; Salazar-Schettino, Paz María

    2015-01-01

    Background Staphylococcus aureus (S. aureus) is one of the major pathogens causing chronic infections. The ability of S. aureus to acquire resistance to a diverse range of antimicrobial compounds results in limited treatment options, particularly in methicillin-resistant S. aureus (MRSA). A mechanism by which S. aureus develops reduced susceptibility to antimicrobials is through the formation of small colony variants (SCVs). Infections by SCVs of S. aureus are an upcoming problem due to difficulties in laboratory diagnosis and resistance to antimicrobial therapy. Methods A prospective study was performed on 120 patients diagnosed with both type 2 diabetes mellitus and infected diabetic foot ulcers. The study was carried out from July 2012 to December 2013 in Hospital General de Mexico. The samples were cultured in blood agar, mannitol salt agar, and MacConkey agar media, and incubated at 37°C in aerobic conditions. Results We describe the first known cases of diabetic foot infections caused by MRSA-SCVs in patients diagnosed with type 2 diabetes mellitus and infected diabetic foot ulcers. In all of our cases, the patients had not received any form of gentamicin therapy. Conclusions The antibiotic therapy commonly used in diabetic patients with infected diabetic foot ulcers fails in the case of MRSA-SCVs because the intracellular location protects S. aureus-SCVs from the host's defenses and also helps them resist antibiotics. The cases studied in this article add to the spectrum of persistent and relapsing infections attributed to MRSA-SCVs and emphasizes that these variants may also play a relevant role in diabetic foot infections. PMID:25787018

  5. Draft Genome Sequences of Vancomycin-Susceptible Staphylococcus aureus Related to Heterogeneous Vancomycin-Intermediate S. aureus.

    PubMed

    Ramaraj, Thiruvarangan; Matyi, Stephanie A; Sundararajan, Anitha; Lindquist, Ingrid E; Devitt, Nicolas P; Schilkey, Faye D; Lamichhane-Khadka, Reena; Hoyt, Peter R; Mudge, Joann; Gustafson, John E

    2014-01-01

    We report the draft genome sequences of three vancomycin-susceptible methicillin-resistant Staphylococcus aureus strains. S. aureus strain MV8 is a sequence type 8 (ST-8) staphylococcal cassette chromosome mec element type IV (SCCmec IV) derivative, while the other two strains (S. aureus MM25 and MM61) are ST-5 SCCmec II strains. MM61 is also closely related to the heterogeneous vancomycin-intermediate S. aureus strain MM66. PMID:25301662

  6. Antibacterial activity of long-chain polyunsaturated fatty acids against Propionibacterium acnes and Staphylococcus aureus.

    PubMed

    Desbois, Andrew P; Lawlor, Keelan C

    2013-11-01

    New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32-1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15-30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

  7. Antibacterial Activity of Long-Chain Polyunsaturated Fatty Acids against Propionibacterium acnes and Staphylococcus aureus

    PubMed Central

    Desbois, Andrew P.; Lawlor, Keelan C.

    2013-01-01

    New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32–1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15–30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

  8. Nanoscale Plasma Coating Inhibits Formation of Staphylococcus aureus Biofilm.

    PubMed

    Xu, Yuanxi; Jones, John E; Yu, Haiqing; Yu, Qingsong; Christensen, Gordon D; Chen, Meng; Sun, Hongmin

    2015-12-01

    Staphylococcus aureus commonly infects medical implants or devices, with devastating consequences for the patient. The infection begins with bacterial attachment to the device, followed by bacterial multiplication over the surface of the device, generating an adherent sheet of bacteria known as a biofilm. Biofilms resist antimicrobial therapy and promote persistent infection, making management difficult to futile. Infections might be prevented by engineering the surface of the device to discourage bacterial attachment and multiplication; however, progress in this area has been limited. We have developed a novel nanoscale plasma coating technology to inhibit the formation of Staphylococcus aureus biofilms. We used monomeric trimethylsilane (TMS) and oxygen to coat the surfaces of silicone rubber, a material often used in the fabrication of implantable medical devices. By quantitative and qualitative analysis, the TMS/O2 coating significantly decreased the in vitro formation of S. aureus biofilms; it also significantly decreased in vivo biofilm formation in a mouse model of foreign-body infection. Further analysis demonstrated TMS/O2 coating significantly changed the protein adsorption, which could lead to reduced bacterial adhesion and biofilm formation. These results suggest that TMS/O2 coating can be used to effectively prevent medical implant-related infections. PMID:26369955

  9. Predictors of Staphylococcus aureus Colonization and Results after Decolonization.

    PubMed

    Malcolm, Tennison L; Robinson, Le Don; Klika, Alison K; Ramanathan, Deepak; Higuera, Carlos A; Murray, Trevor G

    2016-01-01

    Protocols for the screening and decolonization of Staphylococcus aureus prior to total joint arthroplasty (TJA) have become widely adopted. The goals of this study were to determine: (1) whether implementation of a screening protocol followed by decolonization with mupirocin/vancomycin and chlorhexidine reduces the risk of revision compared with no screening protocol (i.e., chlorhexidine alone) and (2) whether clinical criteria could reliably predict colonization with MSSA and/or MRSA. Electronic medical records of primary patients undergoing TJA that were screened (n = 3,927) and were not screened (n = 1,751) for Staphylococcus aureus at least 4 days prior to surgery, respectively, were retrospectively reviewed. All patients received chlorhexidine body wipes preoperatively. Patients carrying MSSA and MRSA were treated preoperatively with mupirocin and vancomycin, respectively, along with the standard preoperative antibiotics and chlorhexidine body wipes. Screened patients were 50% less likely to require revision due to prosthetic joint infection compared to those not screened (p = 0.04). Multivariate regression models were poorly accurate in predicting colonization with MSSA (AUC = 0.58) and MRSA (AUC = 0.62). These results support the routine screening and decolonization of S. aureus prior to TJA. PMID:27528869

  10. Predictors of Staphylococcus aureus Colonization and Results after Decolonization

    PubMed Central

    Malcolm, Tennison L.; Robinson, Le Don; Klika, Alison K.; Ramanathan, Deepak; Higuera, Carlos A.

    2016-01-01

    Protocols for the screening and decolonization of Staphylococcus aureus prior to total joint arthroplasty (TJA) have become widely adopted. The goals of this study were to determine: (1) whether implementation of a screening protocol followed by decolonization with mupirocin/vancomycin and chlorhexidine reduces the risk of revision compared with no screening protocol (i.e., chlorhexidine alone) and (2) whether clinical criteria could reliably predict colonization with MSSA and/or MRSA. Electronic medical records of primary patients undergoing TJA that were screened (n = 3,927) and were not screened (n = 1,751) for Staphylococcus aureus at least 4 days prior to surgery, respectively, were retrospectively reviewed. All patients received chlorhexidine body wipes preoperatively. Patients carrying MSSA and MRSA were treated preoperatively with mupirocin and vancomycin, respectively, along with the standard preoperative antibiotics and chlorhexidine body wipes. Screened patients were 50% less likely to require revision due to prosthetic joint infection compared to those not screened (p = 0.04). Multivariate regression models were poorly accurate in predicting colonization with MSSA (AUC = 0.58) and MRSA (AUC = 0.62). These results support the routine screening and decolonization of S. aureus prior to TJA. PMID:27528869

  11. Nanoscale Plasma Coating Inhibits Formation of Staphylococcus aureus Biofilm

    PubMed Central

    Xu, Yuanxi; Jones, John E.; Yu, Haiqing; Yu, Qingsong; Christensen, Gordon D.

    2015-01-01

    Staphylococcus aureus commonly infects medical implants or devices, with devastating consequences for the patient. The infection begins with bacterial attachment to the device, followed by bacterial multiplication over the surface of the device, generating an adherent sheet of bacteria known as a biofilm. Biofilms resist antimicrobial therapy and promote persistent infection, making management difficult to futile. Infections might be prevented by engineering the surface of the device to discourage bacterial attachment and multiplication; however, progress in this area has been limited. We have developed a novel nanoscale plasma coating technology to inhibit the formation of Staphylococcus aureus biofilms. We used monomeric trimethylsilane (TMS) and oxygen to coat the surfaces of silicone rubber, a material often used in the fabrication of implantable medical devices. By quantitative and qualitative analysis, the TMS/O2 coating significantly decreased the in vitro formation of S. aureus biofilms; it also significantly decreased in vivo biofilm formation in a mouse model of foreign-body infection. Further analysis demonstrated TMS/O2 coating significantly changed the protein adsorption, which could lead to reduced bacterial adhesion and biofilm formation. These results suggest that TMS/O2 coating can be used to effectively prevent medical implant-related infections. PMID:26369955

  12. Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus.

    PubMed

    Mohamed, Mohamed F; Abdelkhalek, Ahmed; Seleem, Mohamed N

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue β-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections. PMID:27405275

  13. Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus

    PubMed Central

    Mohamed, Mohamed F.; Abdelkhalek, Ahmed; Seleem, Mohamed N.

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue β-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections. PMID:27405275

  14. Staphylococcus aureus epidemic in a neonatal nursery: a strategy of infection control.

    PubMed

    Bertini, Giovanna; Nicoletti, PierLuigi; Scopetti, Franca; Manoocher, Pourshaban; Dani, Carlo; Orefici, Graziella

    2006-08-01

    The risk of nosocomial infection due to Staphylococcus aureus in fullterm newborns is higher under hospital conditions where there are overcrowded nurseries and inadequate infection control techniques. We report on an outbreak of skin infection in a Maternity Nursery (May 21, 2000) and the measures undertaken to bring the epidemic under control. These measures included: separating neonates already present in the nursery on August 23, 2000 from ones newly arriving by creating two different cohorts, one of neonates born before this date and one of neonates born later; restricting healthcare workers caring for S. aureus- infected infants from working with non-infected infants; disallowing carrier healthcare workers from caring for patients; introducing contact and droplet precautions (including the routine use of gowns, gloves, and mask); ensuring appropriate disinfection of potential sources of contamination. A representative number of isolates were typed by genomic DNA restriction length polymorphism analysis by means of pulsed-field gel electrophoresis (PFGE). Among the 227 cases of skin lesions, microbiological laboratory analyses confirmed that 175 were staphylococcal infections. The outbreak showed a gradual reduction in magnitude when the overcrowding of the Nursery was reduced by separating the newborns into the two different Nurseries (two cohorts). The genotyping of the strains by PFGE confirmed the nurse-to-newborn transmission of S. aureus. The measures adopted for controlling the S. aureus outbreak can, in retrospect, be assessed to have been very effective. PMID:16602005

  15. Adherence to a metal, polymer and composite by Staphylococcus aureus and Staphylococcus epidermidis.

    PubMed

    Verheyen, C C; Dhert, W J; de Blieck-Hogervorst, J M; van der Reijden, T J; Petit, P L; de Groot, K

    1993-04-01

    Bacterial adherence on to several materials with a potential application in reconstructive surgery was studied. Polymer (poly(L-lactide)), composite (hydroxyapatite/poly(L-lactide)) and metal (316L stainless steel) were evaluated both as smooth and sandblasted specimens. All materials were incubated in phosphate-buffered saline, challenged with Staphylococcus aureus or S. epidermidis and evaluated for up to 24 h. S. aureus showed a preference for the metal and composite tested over the polymer used. For S. epidermidis no preference was found for one of the investigated materials. The influence of surface roughness on bacterial growth was demonstrated by increased colonization on the sandblasted specimens. PMID:8507783

  16. The effect of antibacterial soap with 1.5% triclocarban on Staphylococcus aureus in patients with atopic dermatitis.

    PubMed

    Breneman, D L; Hanifin, J M; Berge, C A; Keswick, B H; Neumann, P B

    2000-10-01

    This double-blind study determined whether daily bathing with an antibacterial soap would reduce the number of Staphylococcus aureus on the skin and result in clinical improvement of atopic dermatitis. For 9 weeks, 50 patients with moderately severe atopic dermatitis bathed daily with either an antimicrobial soap containing 1.5% triclocarban or the placebo soap. They also used a nonmedicated moisturizer and 0.025% triamcinolone acetonide cream as needed, but the availability of the corticosteroid cream was discontinued after 6 weeks. The antimicrobial soap regimen caused significantly greater improvement in the severity and extent of skin lesions than the placebo soap regimen, which correlated with reductions both in S aureus in patients with positive cultures at baseline and in total aerobic organisms. Outcome measures included reductions in S aureus, total aerobic organisms, and dermatologic assessments. Overall, daily bathing with an antibacterial soap was well tolerated, provided clinical improvement, and reduced levels of skin microorganisms. PMID:11109156

  17. High Prevalence of Methicillin-Resistant Staphylococcus aureus among Patients with Septic Arthritis Caused by Staphylococcus aureus

    PubMed Central

    Lin, Wei-Ting; Wu, Chung-Da; Cheng, Shun-Chien; Chiu, Chong-Chi; Tseng, Chi-Chou; Chan, Huan-Tee; Chen, Po-Yih; Chao, Chien-Ming

    2015-01-01

    Background This study investigated the clinical characteristics of patients with septic arthritis caused by Staphylococcus aureus and tried to identify the risk factors for methicillin-resistant S. aureus (MRSA) arthritis. Methods Between January 2008 and December 2011, patients with septic arthritis caused by S. aureus were identified from the computerized databases of a regional hospital and a medical center in southern Taiwan. The medical records of these patients were retrospectively reviewed. Results A total of 93 patients with S. aureus arthritis were identified, and MRSA arthritis was found in 38 (40.9%) cases. The mean age of the patients was 58 years, and 86 (92.5%) episodes were classified as community-acquired infections. Diabetes mellitus (n = 41, 44.1%) was the most common underlying disease, followed by chronic kidney disease and liver cirrhosis. Patients with MRSA arthritis were more frequently elderly and found in the setting of healthcare-associated infection than patients with methicillin-susceptible S. aureus (MSSA) infections. No other significant differences in clinical manifestations and outcomes were noted between these two groups of patients. Overall, the in-hospital mortality rate was 5.4%, and diabetes mellitus was the only risk factor for mortality. Conclusions MRSA is emerging in the setting of community-acquired septic arthritis. MRSA septic arthritis is more likely to develop in the elderly and in healthcare-associated infections than MSSA septic arthritis. PMID:25996145

  18. AraC-Type Regulator Rsp Adapts Staphylococcus aureus Gene Expression to Acute Infection.

    PubMed

    Li, Tianming; He, Lei; Song, Yan; Villaruz, Amer E; Joo, Hwang-Soo; Liu, Qian; Zhu, Yuanjun; Wang, Yanan; Qin, Juanxiu; Otto, Michael; Li, Min

    2016-03-01

    Staphylococcus aureus is an important human pathogen that can cause two categories of severe infections. Acute infections are characterized by pronounced toxin production, while chronic infections often involve biofilm formation. However, it is poorly understood how S. aureus controls the expression of genes associated with acute versus biofilm-associated virulence. We here identified an AraC-type transcriptional regulator, Rsp, that promotes the production of key toxins while repressing major biofilm-associated genes and biofilm formation. Genome-wide transcriptional analysis and modeling of regulatory networks indicated that upregulation of the accessory gene regulator (Agr) and downregulation of the ica operon coding for the biofilm exopolysaccharide polysaccharide intercellular adhesin (PIA) were central to the regulatory impact of Rsp on virulence. Notably, the Rsp protein directly bound to the agrP2 and icaADBC promoters, resulting in strongly increased levels of the Agr-controlled toxins phenol-soluble modulins (PSMs) and alpha-toxin and reduced production of PIA. Accordingly, Rsp was essential for the development of bacteremia and skin infection, representing major types of acute S. aureus infection. Our findings give important insight into how S. aureus adapts the expression of its broad arsenal of virulence genes to promote different types of disease manifestations and identify the Rsp regulator as a potential target for strategies to control acute S. aureus infection. PMID:26712209

  19. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks.

    PubMed Central

    Kluytmans, J; van Belkum, A; Verbrugh, H

    1997-01-01

    Staphylococcus aureus has long been recognized as an important pathogen in human disease. Due to an increasing number of infections caused by methicillin-resistant S. aureus (MRSA) strains, therapy has become problematic. Therefore, prevention of staphylococcal infections has become more important. Carriage of S. aureus appears to play a key role in the epidemiology and pathogenesis of infection. The ecological niches of S. aureus are the anterior nares. In healthy subjects, over time, three patterns of carriage can be distinguished: about 20% of people are persistent carriers, 60% are intermittent carriers, and approximately 20% almost never carry S. aureus. The molecular basis of the carrier state remains to be elucidated. In patients who repeatedly puncture the skin (e.g., hemodialysis or continuous ambulatory peritoneal dialysis [CAPD] patients and intravenous drug addicts) and patients with human immunodeficiency virus (HIV) infection, increased carriage rates are found. Carriage has been identified as an important risk factor for infection in patients undergoing surgery, those on hemodialysis or CAPD, those with HIV infection and AIDS, those with intravascular devices, and those colonized with MRSA. Elimination of carriage has been found to reduce the infection rates in surgical patients and those on hemodialysis and CAPD. Elimination of carriage appears to be an attractive preventive strategy in patients at risk. Further studies are needed to optimize this strategy and to define the groups at risk. PMID:9227864

  20. ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

    PubMed Central

    Daly, Seth M.; Elmore, Bradley O.; Kavanaugh, Jeffrey S.; Triplett, Kathleen D.; Figueroa, Mario; Raja, Huzefa A.; El-Elimat, Tamam; Crosby, Heidi A.; Femling, Jon K.; Cech, Nadja B.; Horswill, Alexander R.; Oberlies, Nicholas H.

    2015-01-01

    Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibility to host killing. Staphylococcus aureus is a major cause of invasive skin and soft tissue infections (SSTIs) in both the hospital and community settings, and it is also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by the accessory gene regulator (agr) controls virulence factor production essential for causing SSTIs. We recently identified ω-hydroxyemodin (OHM), a polyhydroxyanthraquinone isolated from solid-phase cultures of Penicillium restrictum, as a suppressor of QS and a compound sought for the further characterization of the mechanism of action. At concentrations that are nontoxic to eukaryotic cells and subinhibitory to bacterial growth, OHM prevented agr signaling by all four S. aureus agr alleles. OHM inhibited QS by direct binding to AgrA, the response regulator encoded by the agr operon, preventing the interaction of AgrA with the agr P2 promoter. Importantly, OHM was efficacious in a mouse model of S. aureus SSTI. Decreased dermonecrosis with OHM treatment was associated with enhanced bacterial clearance and reductions in inflammatory cytokine transcription and expression at the site of infection. Furthermore, OHM treatment enhanced the immune cell killing of S. aureus in vitro in an agr-dependent manner. These data suggest that bacterial disarmament through the suppression of S. aureus QS may bolster the host innate immune response and limit inflammation. PMID:25645827

  1. Lysostaphin Disrupts Staphylococcus aureus and Staphylococcus epidermidis Biofilms on Artificial Surfaces

    PubMed Central

    Wu, Julie A.; Kusuma, Caroline; Mond, James J.; Kokai-Kun, John F.

    2003-01-01

    Staphylococci often form biofilms, sessile communities of microcolonies encased in an extracellular matrix that adhere to biomedical implants or damaged tissue. Infections associated with biofilms are difficult to treat, and it is estimated that sessile bacteria in biofilms are 1,000 to 1,500 times more resistant to antibiotics than their planktonic counterparts. This antibiotic resistance of biofilms often leads to the failure of conventional antibiotic therapy and necessitates the removal of infected devices. Lysostaphin is a glycylglycine endopeptidase which specifically cleaves the pentaglycine cross bridges found in the staphylococcal peptidoglycan. Lysostaphin kills Staphylococcus aureus within minutes (MIC at which 90% of the strains are inhibited [MIC90], 0.001 to 0.064 μg/ml) and is also effective against Staphylococcus epidermidis at higher concentrations (MIC90, 12.5 to 64 μg/ml). The activity of lysostaphin against staphylococci present in biofilms compared to those of other antibiotics was, however, never explored. Surprisingly, lysostaphin not only killed S. aureus in biofilms but also disrupted the extracellular matrix of S. aureus biofilms in vitro on plastic and glass surfaces at concentrations as low as 1 μg/ml. Scanning electron microscopy confirmed that lysostaphin eradicated both the sessile cells and the extracellular matrix of the biofilm. This disruption of S. aureus biofilms was specific for lysostaphin-sensitive S. aureus, as biofilms of lysostaphin-resistant S. aureus were not affected. High concentrations of oxacillin (400 μg/ml), vancomycin (800 μg/ml), and clindamycin (800 μg/ml) had no effect on the established S. aureus biofilms in this system, even after 24 h. Higher concentrations of lysostaphin also disrupted S. epidermidis biofilms. PMID:14576095

  2. Purification and characterization of aminoglycoside-modifying enzymes from Staphylococcus aureus and Staphylococcus epidermidis.

    PubMed Central

    Ubukata, K; Yamashita, N; Gotoh, A; Konno, M

    1984-01-01

    Several strains of Staphylococcus aureus and Staphylococcus epidermidis, exhibiting characteristic resistance patterns to aminoglycoside antibiotics, were examined. The aminoglycoside-modifying enzymes from these strains were purified by DEAE-Sephadex A-50 chromatography, affinity chromatography, and Sephadex G-100 gel filtration. Three enzymes, a 3'-phosphotransferase III (molecular weight, 31,000; pI 4.1), a bifunctional enzyme having 6'-acetyltransferase and 2"-phosphotransferase (molecular weight, 56,000; pI 4.1) activity, and a 4'4"-adenylytransferase (molecular weight, 34,000; pI 4.7), were isolated from crude extracts of the resistant strains. Aminoglycoside-modifying enzymes with identical enzymatic properties derived from S. aureus and S. epidermidis were also immunologically identical. Images PMID:6331299

  3. Manipulation of Autophagy in Phagocytes Facilitates Staphylococcus aureus Bloodstream Infection

    PubMed Central

    O'Keeffe, Kate M.; Wilk, Mieszko M.; Leech, John M.; Murphy, Alison G.; Laabei, Maisem; Monk, Ian R.; Massey, Ruth C.; Lindsay, Jodi A.; Foster, Timothy J.; Geoghegan, Joan A.

    2015-01-01

    The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium. Using bone marrow-derived DCs (BMDCs), we demonstrate for the first time that DCs can effectively kill S. aureus but that certain strains of S. aureus have the capacity to evade DC (and macrophage) killing by manipulation of autophagic pathways. Strains with high levels of Agr activity were capable of causing autophagosome accumulation, were not killed by BMDCs, and subsequently escaped from the phagocyte, exerting significant cytotoxic effects. Conversely, strains that exhibited low levels of Agr activity failed to accumulate autophagosomes and were killed by BMDCs. Inhibition of the autophagic pathway by treatment with 3-methyladenine restored the bactericidal effects of BMDCs. Using an in vivo model of systemic infection, we demonstrated that the ability of S. aureus strains to evade phagocytic cell killing and to survive temporarily within phagocytes correlated with persistence in the periphery and that this effect is critically Agr dependent. Taken together, our data suggest that strains of S. aureus exhibiting high levels of Agr activity are capable of blocking autophagic flux, leading to the accumulation of autophagosomes. Within these autophagosomes, the bacteria are protected from phagocytic killing, thus providing an intracellular survival niche within professional phagocytes, which ultimately facilitates dissemination. PMID:26099586

  4. Response of corneal epithelial cells to Staphylococcus aureus

    PubMed Central

    2010-01-01

    Staphylococcus aureus is a leading cause of invasive infection. It also infects wet mucosal tissues including the cornea and conjunctiva. Conflicting evidence exists on the expression of Toll-like receptors by human corneal epithelial cells. It was therefore of interest to determine how epithelial cells from this immune privileged tissue respond to S. aureus. Further, it was of interest to determine whether cytolytic toxins, with the potential to cause ion flux or potentially permit effector molecule movement across the target cell membrane, alter the response. Microarrays were used to globally assess the response of human corneal epithelial cells to S. aureus. A large increase in abundance of transcripts encoding the antimicrobial dendritic cell chemokine, CCL20, was observed. CCL20 release into the medium was detected, and this response was found to be largely TLR2 and NOD2 independent. Corneal epithelial cells also respond to S. aureus by increasing the intracellular abundance of mRNA for inflammatory mediators, transcription factors, and genes related to MAP kinase pathways, in ways similar to other cell types. The corneal epithelial cell response was surprisingly unaffected by toxin exposure. Toxin exposure did, however, induce a stress response. Although model toxigenic and non-toxigenic strains of S. aureus were employed in the present study, the results obtained were strikingly similar to those reported for stimulation of vaginal epithelial cells by clinical toxic shock toxin expressing isolates, demonstrating that the initial epithelial cellular responses to S. aureus are largely independent of strain as well as epithelial cell tissue source. PMID:21178447

  5. Subinhibitory Concentrations of Linezolid Reduce Staphylococcus aureus Virulence Factor Expression

    PubMed Central

    Bernardo, Katussevani; Pakulat, Norbert; Fleer, Silke; Schnaith, Annabelle; Utermöhlen, Olaf; Krut, Oleg; Müller, Stefan; Krönke, Martin

    2004-01-01

    The influence of the antibiotic linezolid on the secretion of exotoxins by Staphylococcus aureus was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot analysis. S. aureus suspensions were treated with grading subinhibitory concentrations of linezolid (12.5, 25, 50, and 90% of MIC) at different stages of bacterial growth (i.e., an optical density at 540 nm [OD540] of 0.05 or 0.8). When added to S. aureus cultures at an OD540 of 0.05, linezolid reduced in a dose-dependent manner the secretion of specific virulence factors, including staphylococcal enterotoxin A (SEA) and SEB, bifunctional autolysin, autolysin, protein A, and alpha- and beta-hemolysins. In contrast, other presumably nontoxic exoproteins remained unchanged or even accumulated in supernatants in the presence of linezolid at a 90% MIC. Similarily, when added at OD540 of 0.8, that is, after quorum sensing, linezolid reduced the release of virulence factors, whereas the relative abundance of nontoxic exoproteins such as triacylglycerol lipase, glycerol ester hydrolase, DnaK, or translation elongation factor EF-Tu was found to be increased. Consistently, linezolid reduced in a dose-dependent manner the tumor necrosis factor-inducing activity secreted by S. aureus into the culture supernatants. The results of our study suggest that the expression of virulence factors in S. aureus is especially sensitive to the inhibition of protein synthesis by linezolid, which should be an advantage in the treatment of infections with toxin-producing S. aureus. PMID:14742208

  6. Community-Associated Methicillin-Resistant Staphylococcus aureus Case Studies

    PubMed Central

    Sowash, Madeleine G.; Uhlemann, Anne-Catrin

    2014-01-01

    Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations. PMID:24085688

  7. Cell wall sorting of lipoproteins in Staphylococcus aureus.

    PubMed Central

    Navarre, W W; Daefler, S; Schneewind, O

    1996-01-01

    Many surface proteins are thought to be anchored to the cell wall of gram-positive organisms via their C termini, while the N-terminal domains of these molecules are displayed on the bacterial surface. Cell wall anchoring of surface proteins in Staphylococcus aureus requires both an N-terminal leader peptide and a C-terminal cell wall sorting signal. By fusing the cell wall sorting of protein A to the C terminus of staphylococcal beta-lactamase, we demonstrate here that lipoproteins can also be anchored to the cell wall of S. aureus. The topology of cell wall-anchored beta-lactamase is reminiscent of that described for Braun's murein lipoprotein in that the N terminus of the polypeptide chain is membrane anchored whereas the C-terminal end is tethered to the bacterial cell wall. PMID:8550464

  8. Cavity Forming Pneumonia Due to Staphylococcus aureus Following Dengue Fever.

    PubMed

    Miyata, Nobuyuki; Yoshimura, Yukihiro; Tachikawa, Natsuo; Amano, Yuichiro; Sakamoto, Yohei; Kosuge, Youko

    2015-11-01

    While visiting Malaysia, a 22-year-old previously healthy Japanese man developed myalgia, headache, and fever, leading to a diagnosis of classical dengue fever. After improvement and returning to Japan after a five day hospitalization, he developed productive cough several days after defervescing from dengue. Computed tomography (CT) thorax scan showed multiple lung cavities. A sputum smear revealed leukocytes with phagocytized gram-positive cocci in clusters, and grew an isolate Staphylococcus aureus sensitive to semi-synthetic penicillin; he was treated successfully with ceftriaxone and cephalexin. This second reported case of pneumonia due to S. aureus occurring after dengue fever, was associated both with nosocomial exposure and might have been associated with dengue-associated immunosuppression. Clinicians should pay systematic attention to bacterial pneumonia following dengue fever to establish whether such a connection is causally associated. PMID:26304914

  9. Peptidoglycan architecture can specify division planes in Staphylococcus aureus.

    PubMed

    Turner, Robert D; Ratcliffe, Emma C; Wheeler, Richard; Golestanian, Ramin; Hobbs, Jamie K; Foster, Simon J

    2010-01-01

    Division in Staphylococci occurs equatorially and on specific sequentially orthogonal planes in three dimensions, resulting, after incomplete cell separation, in the 'bunch of grapes' cluster organization that defines the genus. The shape of Staphylococci is principally maintained by peptidoglycan. In this study, we use Atomic Force Microscopy (AFM) and fluorescence microscopy with vancomycin labelling to examine purified peptidoglycan architecture and its dynamics in Staphylococcus aureus and correlate these with the cell cycle. At the presumptive septum, cells were found to form a large belt of peptidoglycan in the division plane before the centripetal formation of the septal disc; this often had a 'piecrust' texture. After division, the structures remain as orthogonal ribs, encoding the location of past division planes in the cell wall. We propose that this epigenetic information is used to enable S. aureus to divide in sequentially orthogonal planes, explaining how a spherical organism can maintain division plane localization with fidelity over many generations. PMID:20975691

  10. Attenuating Staphylococcus aureus Virulence Gene Regulation: A Medicinal Chemistry Perspective

    PubMed Central

    2013-01-01

    Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in experimental models. In this Perspective, we will provide insights into medicinal chemistry strategies for the development of chemical reagents that have the capacity to inhibit staphylococcal virulence expression. These reagents can be broadly grouped into four categories: (1) competitive inhibitors of the accessory gene regulator (agr) quorum sensing system, (2) inhibitors of AgrA–DNA interactions, (3) RNAIII transcription inhibitors, and (4) inhibitors of the SarA family of transcriptional regulators. We discuss the potential of specific examples of antivirulence agents for the management and treatment of staphylococcal infections. PMID:23294220

  11. Strain Discrimination of Staphylococcus aureus Using Superantigen Profiles.

    PubMed

    Tsen, Hau-Yang; Li, Sheng-Chih; Chiang, Yu-Cheng; Tsai, Shuo-Wen

    2016-01-01

    Staphylococcus aureus is one of the major bacterial species that may cause clinical infection and food-poisoning cases. Strains of this species may produce a series of superantigens (SAgs). Due to the importance of staphylococcal infections, reliable methods for the discrimination of strains of this species are important. Such data may allow us to trace the infection origins and be used for epidemiological study. For strain discrimination, genotyping methods, such as pulsed-field gel electrophoresis (PFGE), random amplified polymorphic DNA (RAPD), and multi-locus sequence typing (MLST), etc., could be used. Recently, toxin gene profiles, which can be used for the elucidation of the genetic and pathogenic relatedness between strains, also have been used to improve the strain discrimination. For S. aureus, as more SAg genes were discovered, the SAg profiles become more useful for the strain discrimination of S. aureus. In this chapter, a method for the discrimination of S. aureus strains using superantigen profiles will be described in detail. PMID:26676035

  12. Staphylococcus aureus toxins--their functions and genetics.

    PubMed

    Grumann, Dorothee; Nübel, Ulrich; Bröker, Barbara M

    2014-01-01

    The outcome of encounters between Staphylococcus (S.) aureus and its human host ranges from life-threatening infection through allergic reactions to symptom-free colonization. The pan-genome of this bacterial species encodes numerous toxins, known or strongly suspected to cause specific diseases or symptoms. Three toxin families are in the focus of this review, namely (i) pore-forming toxins, (ii) exfoliative toxins and (iii) superantigens. The majority of toxin-encoding genes are located on mobile genetic elements (MGEs), resulting in a pronounced heterogeneity in the endowment with toxin genes of individual S. aureus strains. Recent population genomic analysis have provided a framework for an improved understanding of the temporal and spatial scales of the motility of MGEs and their associated toxin genes. The distribution of toxin genes among clonal lineages within the species S. aureus is not random, and phylogenetic (sub-)lineages within clonal complexes feature characteristic toxin signatures. When studying pathogenesis, this lineage association, which is caused by the clonal nature of S. aureus makes it difficult to discriminate effects of specific toxins from contributions of the genetic background and/or other associated genetic factors. PMID:23541411

  13. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection.

    PubMed

    Kim, Choon K; Karau, Melissa J; Greenwood-Quaintance, Kerryl E; Tilahun, Ashenafi Y; David, Chella S; Mandrekar, Jayawant N; Patel, Robin; Rajagopalan, Govindarajan

    2015-03-01

    Staphylococcus aureus is a common cause of prosthetic joint infection (PJI). The prevalence of superantigens (SAgs) among PJI-associated S. aureus is unknown. Eighty-four S. aureus isolates associated with PJI isolated between 1999 and 2006 were studied. SAg genes, sea, seb, sec, sed, see, seg, seh, sei, and tst, were assayed by PCR. Seventy-eight (92.9%) isolates carried at least 1 SAg gene studied, with 61 (72.6%) harboring more than 1. seg was most commonly (70.2%), and seh was least frequently (4.8%) detected. tst-positive isolates were associated with early infection and increased erythrocyte sedimentation rate at diagnosis (P=0.006 and P=0.021, respectively). seg and sei were associated with methicillin resistance (P=0.008 and P=0.002, respectively). A majority of PJI-associated isolates studied produced biologically active SAgs in both planktonic and biofilm growth modes. SAg genes are prevalent in S. aureus causing PJI. PMID:25619753

  14. Riccardin C derivatives cause cell leakage in Staphylococcus aureus.

    PubMed

    Morita, Daichi; Sawada, Hiromi; Ogawa, Wakano; Miyachi, Hiroyuki; Kuroda, Teruo

    2015-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major problem in clinical settings, and because it is resistant to most antimicrobial agents, MRSA infections are difficult to treat. We previously reported that synthetic macrocyclic bis(bibenzyl) derivatives, which were originally discovered in liverworts, had anti-MRSA activity. However, the action mechanism responsible was unclear. In the present study, we elucidated the action mechanism of macrocyclic bis(bibenzyl) RC-112 and its partial structure, IDPO-9 (2-phenoxyphenol). Survival experiments demonstrated that RC-112 had a bactericidal effect on MRSA, whereas IDPO-9 had bacteriostatic effects. IDPO-9-resistant mutants exhibited cross-resistance to triclosan, but not to RC-112. The mutation was identified in the fabI, enoyl-acyl carrier protein reductase gene, a target of triclosan. We have not yet isolated the RC-112-resistant mutant. On the other hand, the addition of RC-112, unlike IDPO-9, caused the inflow of ethidium and propidium into S. aureus cells. RC-112-dependent ethidium outflow was observed in ethidium-loaded S. aureus cells. Transmission electron microscopy also revealed that S. aureus cells treated with RC-112 had intracellular lamellar mesosomal-like structures. Intracellular Na+ and K+ concentrations were significantly changed by the RC-112 treatment. These results indicated that RC-112 increased membrane permeability to ethidium, propidium, Na+, and K+, and also that the action mechanism of IDPO-9 was different from those of the other compounds. PMID:26003535

  15. Efficacy of two Staphylococcus aureus phage cocktails in cheese production.

    PubMed

    El Haddad, Lynn; Roy, Jean-Pierre; Khalil, Georges E; St-Gelais, Daniel; Champagne, Claude P; Labrie, Steve; Moineau, Sylvain

    2016-01-18

    Staphylococcus aureus is one of the most prevalent pathogenic bacteria contaminating dairy products. In an effort to reduce food safety risks, virulent phages are investigated as antibacterial agents to control foodborne pathogens. The aim of this study was to compare sets of virulent phages, design phage cocktails, and use them in a cocktail to control pathogenic staphylococci in cheese. Six selected phages belonging to the three Caudovirales families (Myoviridae, Siphoviridae, Podoviridae) were strictly lytic, had a broad host range, and did not carry genes coding for virulence traits in their genomes. However, they were sensitive to pasteurization. At MOI levels of 15, 45, and 150, two anti-S. aureus phage cocktails, each containing three phages, one from each of the three phage families, eradicated a 10(6)CFU/g S. aureus population after 14 days of Cheddar cheese curd ripening at 4°C. The use of these phages did not trigger over-production of S. aureus enterotoxin C. The use of phage cocktails and their rotation may prevent the emergence of phage resistant bacterial strains. PMID:26476571

  16. Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus

    PubMed Central

    Wakeman, Catherine A.; Hammer, Neal D.; Stauff, Devin L.; Attia, Ahmed S.; Anzaldi, Laura L.; Dikalov, Sergey I.; Calcutt, M. Wade; Skaar, Eric P.

    2012-01-01

    Summary Staphylococcus aureus is a pathogen that infects multiple anatomical sites leading to a diverse array of diseases. Although vertebrates can restrict the growth of invading pathogens by sequestering iron within haem, S. aureus surmounts this challenge by employing high-affinity haem uptake systems. However, the presence of excess haem is highly toxic, necessitating tight regulation of haem levels. To overcome haem stress, S. aureus expresses the detoxification system HrtAB. In this work, a transposon screen was performed in the background of a haem-susceptible, HrtAB-deficient S. aureus strain to identify the substrate transported by this putative pump and the source of haem toxicity. While a recent report indicates that HrtAB exports haem itself, the haem-resistant mutants uncovered by the transposon selection enabled us to elucidate the cellular factors contributing to haem toxicity. All mutants identified in this screen inactivated the menaquinone (MK) biosynthesis pathway. Deletion of the final steps of this pathway revealed that quinone molecules localizing to the cell membrane potentiate haem-associated superoxide production and subsequent oxidative damage. These data suggest a model in which membrane-associated haem and quinone molecules form a redox cycle that continuously generates semiquinones and reduced haem, both of which react with atmospheric oxygen to produce superoxide. PMID:23043465

  17. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    PubMed

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists. PMID:26962155

  18. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection

    PubMed Central

    Kim, Choon K.; Karau, Melissa J.; Greenwood-Quaintance, Kerryl E.; Tilahun, Ashenafi Y.; David, Chella S.; Mandrekar, Jayawant N.; Patel, Robin; Rajagopalan, Govindarajan

    2014-01-01

    Staphylococcus aureus is a common cause of prosthetic joint infection (PJI). The prevalence of superantigens (SAgs) among PJI-associated S. aureus is unknown. Eighty-four S. aureus isolates associated with PJI isolated between 1999 and 2006 were studied. SAg genes, sea, seb, sec, sed, see, seg, seh, sei and tst, were assayed by PCR. Seventy-eight (92.9%) isolates carried at least one SAg gene studied, with 61 (72.6%) harboring more than one. seg was most commonly (70.2%) and seh was least frequently (4.8%) detected. tst-positive isolates were associated with early infection and increased ESR at diagnosis (P = 0.006 and P = 0.021, respectively). seg and sei were associated with methicillin resistance (P = 0.008 and 0.002, respectively). SAg genes are prevalent in S. aureus causing PJI; a majority of PJI-associated isolates produce biologically active SAgs in both planktonic and biofilm growth modes. PMID:25619753

  19. Human Staphylococcus aureus lineages among Zoological Park residents in Greece

    PubMed Central

    Drougka, E.; Foka, A.; Posantzis, D.; Giormezis, N.; Anastassiou, E.D.; Petinaki, E.; Spiliopoulou, I.

    2015-01-01

    Staphylococcus aureus is a part of the microbiota flora in many animal species. The clonal spread of S. aureus among animals and personnel in a Zoological Park was investigated. Samples were collected from colonized and infected sites among 32 mammals, 11 birds and eight humans. The genes mecA, mecC, lukF/lukS-PV (encoding Panton-Valentine leukocidin, PVL) and tst (toxic shock syndrome toxin-1) were investigated by PCR. Clones were defined by Multilocus Sequence Typing (MLST), spa type and Pulsed-Field Gel Electrophoresis (PFGE). Seven S. aureus isolates were recovered from four animals and one from an employee. All were mecA, mecC and tst–negative, whereas, one carried the PVL genes and was isolated from an infected Squirrel monkey. Clonal analysis revealed the occurrence of seven STs, eight PFGE and five spa types including ones of human origin. Even though a variety of genotypes were identified among S. aureus strains colonizing zoo park residents, our results indicate that colonization with human lineages has indeed occurred. PMID:26623381

  20. Simple method for correct enumeration of Staphylococcus aureus.

    PubMed

    Haaber, J; Cohn, M T; Petersen, A; Ingmer, H

    2016-06-01

    Optical density (OD) measurement is applied universally to estimate cell numbers of microorganisms growing in liquid cultures. It is a fast and reliable method but is based on the assumption that the bacteria grow as single cells of equal size and that the cells are dispersed evenly in the liquid culture. When grown in such liquid cultures, the human pathogen Staphylococcus aureus is characterized by its aggregation of single cells into clusters of variable size. Here, we show that aggregation during growth in the laboratory standard medium tryptic soy broth (TSB) is common among clinical and laboratory S. aureus isolates and that aggregation may introduce significant bias when applying standard enumeration methods on S. aureus growing in laboratory batch cultures. We provide a simple and efficient sonication procedure, which can be applied prior to optical density measurements to give an accurate estimate of cellular numbers in liquid cultures of S. aureus regardless of the aggregation level of the given strain. We further show that the sonication procedure is applicable for accurate determination of cell numbers using agar plate counting of aggregating strains. PMID:27080188

  1. Selective inhibition of Biotin Protein Ligase from Staphylococcus aureus*

    PubMed Central

    Soares da Costa, Tatiana P.; Tieu, William; Yap, Min Y.; Pendini, Nicole R.; Polyak, Steven W.; Sejer Pedersen, Daniel; Morona, Renato; Turnidge, John D.; Wallace, John C.; Wilce, Matthew C. J.; Booker, Grant W.; Abell, Andrew D.

    2012-01-01

    There is a well documented need to replenish the antibiotic pipeline with new agents to combat the rise of drug resistant bacteria. One strategy to combat resistance is to discover new chemical classes immune to current resistance mechanisms that inhibit essential metabolic enzymes. Many of the obvious drug targets that have no homologous isozyme in the human host have now been investigated. Bacterial drug targets that have a closely related human homologue represent a new frontier in antibiotic discovery. However, to avoid potential toxicity to the host, these inhibitors must have very high selectivity for the bacterial enzyme over the human homolog. We have demonstrated that the essential enzyme biotin protein ligase (BPL) from the clinically important pathogen Staphylococcus aureus could be selectively inhibited. Linking biotin to adenosine via a 1,2,3 triazole yielded the first BPL inhibitor selective for S. aureus BPL over the human equivalent. The synthesis of new biotin 1,2,3-triazole analogues using click chemistry yielded our most potent structure (Ki 90 nm) with a >1100-fold selectivity for the S. aureus BPL over the human homologue. X-ray crystallography confirmed the mechanism of inhibitor binding. Importantly, the inhibitor showed cytotoxicity against S. aureus but not cultured mammalian cells. The biotin 1,2,3-triazole provides a novel pharmacophore for future medicinal chemistry programs to develop this new antibiotic class. PMID:22437830

  2. Proteomics of Staphylococcus aureus--current state and future challenges.

    PubMed

    Hecker, Michael; Engelmann, Susanne; Cordwell, Stuart J

    2003-04-01

    This paper presents a short review of the proteome of Staphylococcus aureus, a gram-positive human pathogen of increasing importance for human health as a result of the increasing antibiotic resistance. A proteome reference map is shown which can be used for future studies and is followed by a demonstration of how proteomics could be applied to obtain new information on S. aureus physiology. The proteomic approach can provide new data on the regulation of metabolism as well as of the stress or starvation responses. Proteomic signatures encompassing specific stress or starvation proteins are excellent tools to predict the physiological state of a cell population. Furthermore proteomics is very useful for analysing the size and function of known and unknown regulons and will open a new dimension in the comprehensive understanding of regulatory networks in pathogenicity. Finally, some fields of application of S. aureus proteomics are discussed, including proteomics and strain evaluation, the role of proteomics for analysis of antibiotic resistance or for discovering new targets and diagnostics tools. The review also shows that the post-genome era of S. aureus which began in 2001 with the publication of the genome sequence is still in a preliminary stage, however, the consequent application of proteomics in combination with DNA array techniques and supported by bioinformatics will provide a comprehensive picture on cell physiology and pathogenicity in the near future. PMID:12659740

  3. Targeting Staphylococcus aureus Quorum Sensing with Nonpeptidic Small Molecule Inhibitors

    PubMed Central

    2014-01-01

    A series of 3-oxo-C12-HSL, tetramic acid, and tetronic acid analogues were synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were noncompetitive inhibitors of the autoinducing peptide (AIP) activated AgrC receptor, by altering the activation efficacy of the cognate AIP-1. They appeared to act as negative allosteric modulators and are exemplified by 3-tetradecanoyltetronic acid 17, which reduced nasal cell colonization and arthritis in a murine infection model. PMID:24592914

  4. Haemodialysis nurses knowledge about methicillin-resistant Staphylococcus aureus.

    PubMed

    Lindberg, Maria; Lindberg, Magnus

    2012-06-01

    Healthcare workers may lack knowledge about antibiotic-resistant bacteria and thereby increase the spread of such organisms. The aim of the present study was to describe the relationship between self-rated knowledge and actual knowledge about methicillin-resistant Staphylococcus aureus (MRSA) among 326 Swedish haemodialysis nurses. Data were collected through a postal questionnaire. The findings suggest that ongoing education about MRSA should be provided to haemodialysis nurses, but also that standardised evaluation of adequate knowledge, skills and competencies' regarding safe practices is warranted. Future research should focus on effective mechanisms to ensure that haemodialysis nurses provide safe MRSA care. PMID:22085397

  5. Structural analysis of the surface polysaccharide of Staphylococcus aureus M.

    PubMed Central

    Liau, D F; Hash, J H

    1977-01-01

    The chemical structure of the surface polysaccharide from Staphylococcus aureus M was investigated by a combination of methanolytic, hydrolytic, and chromatographic techniques. The repeating unit that was most consistent with the data was a hexasaccharide composed of N-acetyl-D-aminogalacturonic acid, N-acetyl-D-fucosamine, and taurine in molar ratios of 4:2:1. A disaccharide was isolated and characterized, by combined gas-liquid chromatography-mass spectrometry, as N-acetyl-D-aminogalacturonyl-(1 leads to 3)-N-acetyl-D-fucosamine. Taurine is linked to a carboxyl group of N-acetyl-D-aminogalacturonic acid via an amide bond. PMID:873882

  6. Cataract surgery during active methicillin-resistant Staphylococcus aureus infection

    PubMed Central

    Mansour, Ahmad M; Salti, Haytham I

    2014-01-01

    We present two patients with active, foul-smelling, methicillin-resistant Staphylococcus aureus (MRSA) wounds of the forehead and sternum following craniotomy or open heart surgery. Both had debilitating cataracts and were told by the infectious diseases team that cataract surgery is very risky. Both underwent sequential bilateral phacoemulsification with no sign of infection. Patients with active MRSA wound infections may safely undergo cataract surgery with additional precautions observed intraoperatively (good wound construction) and postoperatively (topical antibiotics and close observation). Banning such surgeries can unnecessarily jeopardize the lifestyles of such patients. PMID:24790402

  7. spa typing for epidemiological surveillance of Staphylococcus aureus.

    PubMed

    Hallin, Marie; Friedrich, Alexander W; Struelens, Marc J

    2009-01-01

    The spa typing method is based on sequencing of the polymorphic X region of the protein A gene (spa), present in all strains of Staphylococcus aureus. The X region is constituted of a variable number of 24-bp repeats flanked by well-conserved regions. This single-locus sequence-based typing method combines a number of technical advantages, such as rapidity, reproducibility, and portability. Moreover, due to its repeat structure, the spa locus simultaneously indexes micro- and macrovariations, enabling the use of spa typing in both local and global epidemiological studies. These studies are facilitated by the establishment of standardized spa type nomenclature and Internet shared databases. PMID:19521876

  8. Inhibition of methicillin resistant Staphylococcus aureus by a plasma needle

    NASA Astrophysics Data System (ADS)

    Miletić, Maja; Vuković, Dragana; Živanović, Irena; Dakić, Ivana; Soldatović, Ivan; Maletić, Dejan; Lazović, Saša; Malović, Gordana; Petrović, Zoran Lj.; Puač, Nevena

    2014-03-01

    In numerous recent papers plasma chemistry of non equilibrium plasma sources operating at atmospheric pressure has been linked to plasma medical effects including sterilization. In this paper we present a study of the effectiveness of an atmospheric pressure plasma source, known as plasma needle, in inhibition of the growth of biofilm produced by methicillin resistant Staphylococcus aureus (MRSA). Even at the lowest powers the biofilms formed by inoculi of MRSA of 104 and 105 CFU have been strongly affected by plasma and growth in biofilms was inhibited. The eradication of the already formed biofilm was not achieved and it is required to go to more effective sources.

  9. Blood–Retinal Barrier Compromise and Endogenous Staphylococcus aureus Endophthalmitis

    PubMed Central

    Coburn, Phillip S.; Wiskur, Brandt J.; Astley, Roger A.; Callegan, Michelle C.

    2015-01-01

    Purpose To test the hypothesis that blood–retinal barrier compromise is associated with the development of endogenous Staphylococcus aureus endophthalmitis. Methods To compromise the blood–retinal barrier in vivo, streptozotocin-induced diabetes was induced in C57BL/6J mice for 1, 3, or 5 months. Diabetic and age-matched nondiabetic mice were intravenously injected with 108 colony-forming units (cfu) of S. aureus, a common cause of endogenous endophthalmitis in diabetics. After 4 days post infection, electroretinography, histology, and bacterial counts were performed. Staphylococcus aureus–induced alterations in in vitro retinal pigment epithelial (RPE) cell barrier structure and function were assessed by anti–ZO-1 immunohistochemistry, FITC-dextran conjugate diffusion, and bacterial transmigration assays. Results We observed one bilateral infection in a control, nondiabetic animal (mean = 1.54 × 103 ± 1.78 × 102 cfu/eye, 7% incidence). Among the 1-month diabetic mice, we observed culture-confirmed unilateral infections in two animals (mean = 5.54 × 102 ± 7.09 × 102 cfu/eye, 12% incidence). Among the 3-month diabetic mice, infections were observed in 11 animals, three with bilateral infections (mean = 2.67 × 102 ± 2.49 × 102 cfu/eye, 58% incidence). Among the 5-month diabetic mice, we observed infections in five animals (mean = 7.88 × 102 ± 1.08 × 103 cfu/eye, 33% incidence). In vitro, S. aureus infection reduced ZO-1 immunostaining and disrupted the barrier function of cultured RPE cells, resulting in diffusion of fluorophore-conjugated dextrans and transmigration of live bacteria across a permeabilized RPE barrier. Conclusions Taken together, these results indicated that S. aureus is capable of inducing blood–retinal barrier permeability and causing endogenous bacterial endophthalmitis in normal and diabetic animals. PMID:26559476

  10. Skin and Soft Tissue Infection (Cellulitis) (Beyond the Basics)

    MedlinePlus

    ... skin infections are discussed separately. (See "Patient education: Methicillin-resistant Staphylococcus aureus (MRSA) (Beyond the Basics)" and "Patient ... be caused by a skin infection known as methicillin-resistant Staphylococcus aureus (MRSA). This is discussed separately. (See " ...

  11. Draft Genome Sequence of Isolate Staphylococcus aureus LHSKBClinical, Isolated from an Infected Hip

    PubMed Central

    Stipetic, Laurence H.; Hamilton, Graham; Dalby, Matthew J.; Davies, Robert L.; Meek, R. M. Dominic; Ramage, Gordon; Smith, David G. E.

    2015-01-01

    We report here the genome sequence of a clinical isolate of Staphylococcus aureus from an orthopedic infection. Phenotypically diverse Staphylococcus aureus strains are associated with orthopedic infections and subsequent implant failure, and some are highly resistant to antibiotics. This genome sequence will support further analyses of strains causing orthopedic infections. PMID:25931597

  12. Community-Acquired Methicillin-Resistant "Staphylococcus aureus": Considerations for School Nurses

    ERIC Educational Resources Information Center

    Alex, Aniltta; Letizia, MariJo

    2007-01-01

    Methicillin-resistant "Staphylococcus aureus" (MRSA) is a disease-causing organism that has been present in hospital settings since the 1960s. However, a genetically distinct strain of MRSA, called community-acquired methicillin-resistant "Staphylococcus aureus" (CA-MRSA), has emerged in recent years in community settings among healthy…

  13. Nasal Carriage of Staphylococcus aureus in Botucatu, Brazil: A Population-Based Survey

    PubMed Central

    Pires, Fabiana Venegas; da Cunha, Maria de Lourdes Ribeiro de Souza; Abraão, Lígia Maria; Martins, Patrícia Y. F.; Camargo, Carlos Henrique; Fortaleza, Carlos Magno Castelo Branco

    2014-01-01

    Recent increases in the incidence and severity of staphylococcal infections renewed interest in studies that assess the burden of asymptomatic carriage of Staphylococcus aureus in the community setting. We conducted a population-based survey in the city of Botucatu, Brazil (122,000 inhabitants), in order to identify the prevalence of nasal carriage of Staphylococcus aureus (including methicillin-resistant strains). Nasal swabs were obtained from 686 persons over one year of age. Resistance to methicillin was assessed through phenotypic methods, identification of the mecA gene and typing of the Staphylococcal Chromosome Cassette mec (SCCmec). Methicillin-resistant S. aureus (MRSA) isolates were characterized using Pulsed-Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST) and spa typing. Polymerase chain reaction was applied to identify genes coding for Panton-Valentine Leukocidin (PVL) in isolates. The prevalence of overall S. aureus carriage was 32.7% (95%CI, 29.2%–36.2%). Carriers were significantly younger (mean age, 28.1 versus 36.3 for non-carriers; OR for age, 0.98; 95%CI, 0.97–0.99) and likely to report recent skin infection (OR, 1.85; 95%CI, 1.03–3.34). Carriage of methicillin-resistant S. aureus (MRSA) was found in 0.9% of study subjects (95%CI, 0.4%–1.8%). All MRSA isolates harbored SCCmec type IV, and belonged to spa types t002 or t021, but none among them harbored genes coding for PLV. In MLST, most isolates belonged to clones ST5 or ST1776. However, we found one subject who carried a novel clone, ST2594. Two out of six MRSA carriers had household contacts colonized with isolates similar to theirs. Our study pointed to dissemination of community-associated MRSA among the Brazilian population. PMID:24663818

  14. Population Genomics of Reduced Vancomycin Susceptibility in Staphylococcus aureus

    PubMed Central

    Rishishwar, Lavanya; Kraft, Colleen S.

    2016-01-01

    ABSTRACT The increased prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) is an emerging health care threat. Genome-based comparative methods hold great promise to uncover the genetic basis of the VISA phenotype, which remains obscure. S. aureus isolates were collected from a single individual that presented with recurrent staphylococcal bacteremia at three time points, and the isolates showed successively reduced levels of vancomycin susceptibility. A population genomic approach was taken to compare patient S. aureus isolates with decreasing vancomycin susceptibility across the three time points. To do this, patient isolates were sequenced to high coverage (~500×), and sequence reads were used to model site-specific allelic variation within and between isolate populations. Population genetic methods were then applied to evaluate the overall levels of variation across the three time points and to identify individual variants that show anomalous levels of allelic change between populations. A successive reduction in the overall levels of population genomic variation was observed across the three time points, consistent with a population bottleneck resulting from antibiotic treatment. Despite this overall reduction in variation, a number of individual mutations were swept to high frequency in the VISA population. These mutations were implicated as potentially involved in the VISA phenotype and interrogated with respect to their functional roles. This approach allowed us to identify a number of mutations previously implicated in VISA along with allelic changes within a novel class of genes, encoding LPXTG motif-containing cell-wall-anchoring proteins, which shed light on a novel mechanistic aspect of vancomycin resistance. IMPORTANCE The emergence and spread of antibiotic resistance among bacterial pathogens are two of the gravest threats to public health facing the world today. We report the development and application of a novel population genomic

  15. Response of Staphylococcus Aureus to a Spaceflight Analogue

    NASA Technical Reports Server (NTRS)

    Castro, S. L.; Ott, C. M.

    2010-01-01

    The decreased gravity of the spaceflight environment creates quiescent, low fluid shear conditions. This environment can impart considerable effects on the physiology of microorganisms as well as their interactions with potential hosts. Using the rotating wall vessel (RWV), as a spaceflight analogue, the consequence of low fluid shear culture on microbial pathogenesis has provided a better understanding of the risks to the astronaut crew from infectious microorganisms. While the outcome of low fluid shear culture has been investigated for several bacterial pathogens, little has been done to understand how this environmental factor affects Staphylococcus aureus. S. aureus is an opportunistic human pathogen which presents a high level of infection risk to the crew, as it has been isolated from both the space shuttle and International Space Station. Given that approximately forty percent of the population are carriers of the bacteria, eradication of this organism from in flight environments is impractical. These reasons have lead to us to assess the response of S. aureus to a reduced fluid shear environment. Culture in the RWV demonstrated that S. aureus grown under the low-shear condition had lower cell concentrations after 10 hours when compared to the control culture. Furthermore, the low-shear cultured bacteria displayed a reduction in carotenoid production, pigments responsible for their yellow/gold coloration. When exposed to various environmental stressors, post low-shear culture, a decrease in the ability to survive oxidative assault was observed compared to control cultures. The low fluid shear environment also resulted in a decrease in hemolysin secretion, a staphylococcal toxin responsible for red blood cell lysis. When challenged by the immune components present in human whole blood, low-shear cultured S. aureus demonstrated significantly reduced survival rates as compared to the control culture. Assays to determine the duration of these alterations

  16. Fluoroquinolone Therapy in Staphylococcus aureus Infections: Where Do We Stand?

    PubMed Central

    Gade, Neeta D; Qazi, Mohiuddin S

    2013-01-01

    Aim: The study aimed to evaluate the utility of various commonly used fluoroquinolones against Staphylococcus aureus isolates. Materials and Methods: A total of 250 isolates of S. aureus were studied from different clinical specimens like blood, pus, wound swabs, sputum, ear swabs, and body fluids between November 2009 and December 2011. All the isolates were tested for their susceptibility to fluoroquinolones and other antimicrobial agents by Kirby-Bauer disc diffusion method using criteria of standard zone of inhibition. Methicillin-resistant S. aureus (MRSA) detection was done by cefoxitin disk diffusion method. The MRSA isolates were tested for minimum inhibitory concentration (MIC) to vancomycin by E-test strips. All the MRSA strains were sent to National Staphylococcal Phage-typing Centre, Maulana Azad Medical College, New Delhi for phage typing. Results: A total of 107 strains of S. aureus (42.8%) were detected as MRSA. Multidrug resistance was observed among the MRSA strains more commonly than among the MSSA stains. Among the fluoroquinolones, maximum resistance in MRSA was seen to ciprofloxacin (92.5%), followed by ofloxacin (80.4%). None of the S. aureus isolates showed resistance to vancomycin and linezolid. The MICs of vancomycin for the MRSA tested ranged from 0.5 to 2 μg/ml. Phage typing pattern of 107 MRSA isolates revealed that 37 (34.6%) MRSA isolates were nontypeable and 70 (65.4%) were typeable. Conclusion: Ciprofloxacin can no longer be used in empirical therapy against MRSA infections. Use of other members of fluoroquinolone should be limited only to those strains that show laboratory confirmation of their susceptibility. Vancomycin remains the drug of choice to treat MRSA infections. PMID:24701103

  17. Heme Recognition By a Staphylococcus Aureus IsdE

    SciTech Connect

    Grigg, J.C.; Vermeiren, C.L.; Heinrichs, D.E.; Murphy, M.E.P.

    2009-06-03

    Staphylococcus aureus is a Gram-positive bacterial pathogen and a leading cause of hospital acquired infections. Because the free iron concentration in the human body is too low to support growth, S. aureus must acquire iron from host sources. Heme iron is the most prevalent iron reservoir in the human body and a predominant source of iron for S. aureus. The iron-regulated surface determinant (Isd) system removes heme from host heme proteins and transfers it to IsdE, the cognate substrate-binding lipoprotein of an ATP-binding cassette transporter, for import and subsequent degradation. Herein, we report the crystal structure of the soluble portion of the IsdE lipoprotein in complex with heme. The structure reveals a bi-lobed topology formed by an N- and C-terminal domain bridged by a single {alpha}-helix. The structure places IsdE as a member of the helical backbone metal receptor superfamily. A six-coordinate heme molecule is bound in the groove established at the domain interface, and the heme iron is coordinated in a novel fashion for heme transporters by Met{sup 78} and His{sup 229}. Both heme propionate groups are secured by H-bonds to IsdE main chain and side chain groups. Of these residues, His{sup 299} is essential for IsdE-mediated heme uptake by S. aureus when growth on heme as a sole iron source is measured. Multiple sequence alignments of homologues from several other Gram-positive bacteria, including the human pathogens pyogenes, Bacillus anthracis, and Listeria monocytogenes, suggest that these other systems function equivalently to S. aureus IsdE with respect to heme binding and transport.

  18. Phenotypic Characteristics of Vancomycin-Non-Susceptible Staphylococcus aureus

    PubMed Central

    Sirichoat, Auttawit; Wongthong, Sujintana; Kanyota, Ratdawan; Tavichakorntrakool, Ratree; Chanawong, Aroonwadee; Welbat, Jariya Umka; Lulitanond, Aroonlug

    2016-01-01

    Background: Staphylococcus aureus, with reduced vancomycin susceptibility, is probably under the regulation of several genes and various express phenotypes. Objectives: This study aimed to investigate the phenotypic differences between vancomycin-susceptible S. aureus (VSSA), vancomycin-intermediate S. aureus (VISA), and heterogeneous VISA (hVISA) isolates. Materials and Methods: A total of 130 methicillin-resistant S. aureus (MRSA) isolates were studied, including 49 VSSA, 28 hVISA, and 5 VISA isolates from blood cultures and 48 isolates (two VSSA, six hVISA, and 40 VISA) derived in vitro (laboratory-induced/sub-passaged). Their phenotypes were examined using a coagulase tube test, colony spreading on soft agar, and urease activity. The SCCmec and agr typing were performed using multiplex PCR. Results: Most of the MRSA isolates were SCCmec III-agr I (84.5%), followed by SCCmec II-agr II (11.8%). The average plasma coagulation time of vancomycin-non-susceptible isolates was longer than that of the susceptible isolates (12 vs. 2.6 hours). Four hVISA (P = 0.023) and nine VISA (P < 0.001) isolates yielded a negative coagulase test after 24-hour incubation. The percentage of VSSA isolates showing non-spreading colonies (accessory gene regulator (agr) dysfunction) was significantly lower than in the VISA group (P = 0.013), but no significant difference was found between VSSA and hVISA. The VISA group showed higher urease activity than that of the VSSA and hVISA groups (P = 0.002). Conclusions: There were diverse phenotypic changes among vancomycin-non-susceptible S. aureus isolates. This may be due to the variety of related regulatory systems. The diversity of phenotypic expression may result in its misidentification in routine laboratory checks. PMID:27099678

  19. Characterization of a mouse-adapted Staphylococcus aureus strain.

    PubMed

    Holtfreter, Silva; Radcliff, Fiona J; Grumann, Dorothee; Read, Hannah; Johnson, Sarah; Monecke, Stefan; Ritchie, Stephen; Clow, Fiona; Goerke, Christiane; Bröker, Barbara M; Fraser, John D; Wiles, Siouxsie

    2013-01-01

    More effective antibiotics and a protective vaccine are desperately needed to combat the 'superbug' Staphylococcus aureus. While in vivo pathogenicity studies routinely involve infection of mice with human S. aureus isolates, recent genetic studies have demonstrated that S. aureus lineages are largely host-specific. The use of such animal-adapted S. aureus strains may therefore be a promising approach for developing more clinically relevant animal infection models. We have isolated a mouse-adapted S. aureus strain (JSNZ) which caused a severe outbreak of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively characterize this strain on a genomic level and determine its virulence potential in murine colonization and infection models. JSNZ belongs to the MLST type ST88, rare among human isolates, and lacks an hlb-converting phage encoding human-specific immune evasion factors. Naive mice were found to be more susceptible to nasal and gastrointestinal colonization with JSNZ than with the human-derived Newman strain. Furthermore, naïve mice required antibiotic pre-treatment to become colonized with Newman. In contrast, JSNZ was able to colonize mice in the absence of antibiotic treatment suggesting that this strain can compete with the natural flora for space and nutrients. In a renal abscess model, JSNZ caused more severe disease than Newman with greater weight loss and bacterial burden. In contrast to most other clinical isolates, JSNZ can also be readily genetically modified by phage transduction and electroporation. In conclusion, the mouse-adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal colonization and for screening novel vaccines and therapies directed at preventing colonization. PMID:24023720

  20. Molecular characterization of α-amylase from Staphylococcus aureus.

    PubMed

    Lakshmi, Hanumanthu Prasanna; Prasad, Uppu Venkateswara; Yeswanth, Sthanikam; Swarupa, Vimjam; Prasad, Osuru Hari; Narasu, Mangamoori Lakshmi; Sarma, Potukuchi Venkata Gurunadha Krishna

    2013-01-01

    Staphylococcus aureus is one of the prominent Gram positive human pathogen secretes many surface and secretary proteins including various enzymes and pathogenic factors that favour the successful colonization and infection of host tissue. α-amylase is one of the enzymes secreted by S. aureus which catalyses the breakdown of complex sugars to monosaccharides, which are required for colonization and survival of this pathogen in any anatomical locales. In the present study we have cloned, sequenced, expressed and characterized α-amylase gene from S. aureus ATCC12600. The recombinant enzyme has a molecular weight of 58kDa and the kinetics showed Vmax 0.0208±0.033 (mg/ml)/mg/min and Km 10.633±0.737mg/ml. The multiple sequence analysis showed α- amylase of S. aureus exhibited large differences with Bacillus subtilis and Streptococcus bovis. As the crystal structure of S. aureus α- amylase was unavailable, we used homology modelling method to build the structure. The built structure was validated by Ramachandran plot which showed 90% of the residues in the allowed region while no residue was found in the disallowed region and the built structure was close to the crystal structure with Z-Score: -6.85. The structural superimposition studies with α- amylases of Bacillus subtilis and Streptococcus bovis showed distinct differences with RMSD values of 18.158Åand 7.091Å respectively which correlated with enzyme kinetics, indicating α-amylase is different among these bacteria. PMID:23559746

  1. Molecular characterization of α-amylase from Staphylococcus aureus

    PubMed Central

    Lakshmi, Hanumanthu Prasanna; Prasad, Uppu Venkateswara; Yeswanth, Sthanikam; Swarupa, Vimjam; Prasad, Osuru Hari; Narasu, Mangamoori Lakshmi; Sarma, Potukuchi Venkata Gurunadha Krishna

    2013-01-01

    Staphylococcus aureus is one of the prominent Gram positive human pathogen secretes many surface and secretary proteins including various enzymes and pathogenic factors that favour the successful colonization and infection of host tissue. α-amylase is one of the enzymes secreted by S. aureus which catalyses the breakdown of complex sugars to monosaccharides, which are required for colonization and survival of this pathogen in any anatomical locales. In the present study we have cloned, sequenced, expressed and characterized α-amylase gene from S. aureus ATCC12600. The recombinant enzyme has a molecular weight of 58kDa and the kinetics showed Vmax 0.0208±0.033 (mg/ml)/mg/min and Km 10.633±0.737mg/ml. The multiple sequence analysis showed α- amylase of S. aureus exhibited large differences with Bacillus subtilis and Streptococcus bovis. As the crystal structure of S. aureus α- amylase was unavailable, we used homology modelling method to build the structure. The built structure was validated by Ramachandran plot which showed 90% of the residues in the allowed region while no residue was found in the disallowed region and the built structure was close to the crystal structure with Z-Score: -6.85. The structural superimposition studies with α- amylases of Bacillus subtilis and Streptococcus bovis showed distinct differences with RMSD values of 18.158Åand 7.091Å respectively which correlated with enzyme kinetics, indicating α-amylase is different among these bacteria. PMID:23559746

  2. Growth kinetics of Staphylococcus aureus on Brie and Camembert cheeses.

    PubMed

    Lee, Heeyoung; Kim, Kyungmi; Lee, Soomin; Han, Minkyung; Yoon, Yohan

    2014-05-01

    In this study, we developed mathematical models to describe the growth kinetics of Staphylococcus aureus on natural cheeses. A five-strain mixture of Staph. aureus was inoculated onto 15 g of Brie and Camembert cheeses at 4 log CFU/g. The samples were then stored at 4, 10, 15, 25, and 30 °C for 2-60 d, with a different storage time being used for each temperature. Total bacterial and Staph. aureus cells were enumerated on tryptic soy agar and mannitol salt agar, respectively. The Baranyi model was fitted to the growth data of Staph. aureus to calculate kinetic parameters such as the maximum growth rate in log CFU units (r max; log CFU/g/h) and the lag phase duration (λ; h). The effects of temperature on the square root of r max and on the natural logarithm of λ were modelled in the second stage (secondary model). Independent experimental data (observed data) were compared with prediction and the respective root mean square error compared with the RMSE of the fit on the original data, as a measure of model performance. The total growth of bacteria was observed at 10, 15, 25, and 30 °C on both cheeses. The r max values increased with storage temperature (P<0·05), but a significant effect of storage temperature on λ values was only observed between 4 and 15 °C (P<0·05). The square root model and linear equation were found to be appropriate for description of the effect of storage temperature on growth kinetics (R 2=0·894-0·983). Our results indicate that the models developed in this study should be useful for describing the growth kinetics of Staph. aureus on Brie and Camembert cheeses. PMID:24731395

  3. Characterization of the ςB Regulon in Staphylococcus aureus

    PubMed Central

    Gertz, Silke; Engelmann, Susanne; Schmid, Roland; Ziebandt, Anne-Kathrin; Tischer, Karsten; Scharf, Christian; Hacker, Jörg; Hecker, Michael

    2000-01-01

    The ςB-dependent stress regulon in gram-positive bacteria might fulfill a physiological role in stress response and virulence similar to that of the ςS regulon in Escherichia coli and other gram-negative bacteria. In order to obtain evidence for the function of the ςB regulon of Staphylococcus aureus, especially in virulence control, ςB-dependent stress genes were identified. The two-dimensional protein pattern of wild-type cells of S. aureus COL was compared with that of an isogenic sigB mutant. By this approach, we found that the synthesis of about 27 cytoplasmic proteins seemed to be under the positive control of ςB. N-terminal sequencing of 18 proteins allowed the identification of their genes on the almost finished genome sequence of S. aureus COL and the analysis of the promoter structure. Transcriptional analyses of 11 of these genes confirmed their ςB dependency, and moreover, about 7 additional ςB-dependent genes were found which are cotranscribed with the newly detected genes, forming operons. Altogether, we identified 23 ςB-dependent genes and their corresponding proteins. Among them are proteins probably involved in the generation of NADH or in membrane transport mechanisms. Furthermore, at least one clpC-homologous gene was localized on the S. aureus sequence solely transcribed by ςB. In contrast, a second clpC-homologous gene in S. aureus forming an operon with ctsR, yacH, and yacI was ςB independently expressed. PMID:11092859

  4. Staphylococcus aureus ST398 from slaughter pigs in northeast China.

    PubMed

    Yan, Xiaomei; Yu, Xiaojie; Tao, Xiaoxia; Zhang, Jianfeng; Zhang, Binghua; Dong, Rui; Xue, Chengyu; Grundmann, Hajo; Zhang, Jianzhong

    2014-05-01

    To describe the prevalence and population structure of Staphylococcus aureus bacteria that colonize pigs at slaughterhouses in northeastern China, nose swabs were collected from pigs in two slaughterhouses in Harbin, Heilongjiang Province, China in 2009. S. aureus isolates were characterized by multilocus sequence typing (MLST), spa typing, SCCmec typing, antimicrobial susceptibility testing and pvl gene detection. A total of 200 S. aureus isolates were collected from 590 pigs (33.9%, 200/590), of which 162 (81%, 162/200) were methicillin-susceptible S. aureus (MSSA) and 38 (19%, 38/200) were methicillin-resistant S. aureus (MRSA). Ninety-nine of the MSSA isolates (99/162, 61.1%) were ST398, which represented the dominant sequence type overall. Eighty-seven isolates were ST9 (87/200, 43.5%), and all MRSA belonged to that sequence type which consisted of the spa types t899 and t2922. Among the MSSA strains, t034, t899 and t4358 were the most dominant spa types (139/162, 85.8%). All MRSA isolates harbored SCCmec type IVb. The pvl gene was only detected in 3 ST7/t2119 MSSA isolates. All MRSA but more importantly also 82.7% (134/162) of the MSSA isolates were resistant to six or more antibiotics. Moreover, a novel resistance determinant-lsa(E) was identified among 22% (44/200) of all isolates. In conclusion, pigs in northeast China are frequently colonized with ST398 MSSA. MRSA with this sequence type, typically associated with pigs in Europe, was not found. High levels of multiple antibiotic resistance among MRSA isolates as well as MSSA isolates are a public health concern. PMID:24418357

  5. Antimicrobial susceptibility of Staphylococcus aureus from retail ground meats.

    PubMed

    Kelman, Alina; Soong, Yee-Ann; Dupuy, Nicole; Shafer, Daniel; Richbourg, William; Johnson, Kourtney; Brown, Twain; Kestler, Edward; Li, Yi; Zheng, Jie; McDermott, Patrick; Meng, Jianghong

    2011-10-01

    The aim of this study was to characterize antimicrobial resistance in Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), recovered from raw retail meat products purchased in the Washington, D.C., area. From March to August 2008, 694 samples of ground beef (n = 198), ground pork (n = 300), and ground turkey (n = 196) were collected by random sampling from stores of three grocery chains. In total, 200 S. aureus isolates (29%) were recovered by direct plating. When tested for susceptibility to 22 antimicrobials, 69% of the S. aureus isolates were resistant to tetracycline, 26% to penicillin, 17% to ampicillin, 13% to methicillin, 8% to erythromycin, 4.5% to clindamycin, 1.5% to gentamicin, and 0.5% to chloramphenicol, oxacillin, cefoxitin, or quinupristin-dalfopristin. However, 27% of the isolates were susceptible to all tested antimicrobials. More turkey and pork isolates were resistant to ampicillin, penicillin, and tetracycline than were beef isolates (P < 0.05). Additionally, 17% of the turkey and 17% of the pork isolates were resistant to methicillin (MIC ≥ 16 μg/ml), whereas no beef isolates were resistant to the antimicrobial agent. A single MRSA (methicillin MIC > 32 μg/ml) isolate containing the mecA gene with additional resistance to erythromycin, clindamycin, oxacillin plus 2% NaCl, cefoxitin, ampicillin, penicillin, quinupristin-dalfopristin, tetracycline, and gentamicin was recovered from one pork sample. The presence of antimicrobial-resistant S. aureus, coupled with the relative lack of such studies in the United States, suggests that further investigations on MRSA in the food supply are needed despite the low rate of MRSA found in this particular study. PMID:22004808

  6. Adhesion of Staphylococcus aureus to implants with different physicochemical characteristics.

    PubMed

    Karlov, A V; Khlusov, I A; Pontak, V A; Ignatov, V P; Ivin, M A; Zinatulina, S Yu

    2002-09-01

    Adhesion of pathogenic Staphylococcus aureus (strain 209) to BT1-0 titanium disks (12 mm in diameter) with different coatings and noncoated was studied in vitro by photocolorimetry. Transparency of bacterial suspension in normal saline was evaluated after 2-h culturing with the implants at 37 degrees C. The decrease of S. aureus content in the suspension due to its adsorption on implants was negligible and increased by 0.9-5.5% in comparison with the control (adhesion to glass). When the specimens were placed into bacterial suspension, the density of staphylococcal adsorption on the surface considerably increased (by 9-53%) in comparison with the control, which attested to active participation of the implants in bacterial adsorption. The degree of bacterial adhesion to the implants decreased in the following order: disk with calcium phosphate ceramic coating-disk with calcium phosphate X-ray amorphous coating-disk without coating-disk with cermet coating. The adhesion of Staphylococcus is a stochastic process depending on the sum of implant characteristics, in particular, on the phase composition of the coating, electric conductivity, and Ca/P ionic ratio. The authors conclude that the formation of antibacterial properties of coating by saturating them with antibiotics or impregnation with metals, specifically silver ion implantation, is justified, because it reduces the postimplantation infection risk. PMID:12512002

  7. Staphylococcus aureus ampicillin-resistant from the odontological clinic environment.

    PubMed

    Bernardo, Wagner Luis de Carvalho; Boriollo, Marcelo Fabiano Gomes; Gonçalves, Reginaldo Bruno; Höfling, José Francisco

    2005-01-01

    The aim of this research was to evaluate the prevalence of Staphylococcus spp. and S. aureus in the odontological clinic environment (air), their production of beta-lactamase and antibacterial susceptibility to the major antibiotics utilized in medical particle. During 12 months of samples collect were isolated 9775 CFU by MSA medium suggesting a high amount of Staphylococcus spp. in the clinic environment which can appear through aerosols. A total of 3149 colonies (32.2%) were suggestive of pathogenic staphylococci. Gram coloration, catalase test, colony-mallow growing on chromogenic medium, and coagulase test confirmed the identity of 44 (0.45%) S. aureus isolates. Of these, 35 isolates (79.5%) showed production of beta-lactamase by Cefinase discs and resistance to ampicillin, erythromycin (7 isolates) and tetracycline (1 isolate) suggesting the existence of multiresistant isolates. The evaluation of the oxacillin MIC by Etest assays showed susceptibility patterns suggesting the inexistence of the mecA gene in chromosomal DNA. These results point out to the need of a larger knowledge on the contamination means and propagation of this microorganism into the odontological clinic. PMID:15729470

  8. Staphylococcus aureus recoveries on various brands of membrane filters.

    PubMed

    Alico, R K; Palenchar, C A

    1975-10-01

    Six commercial brands of membrane filters were compared using staphylococcus aureus obtained from pure cultures and from swimming pool water. The following brands of filters were tested: Gelman, Millipore, Nuclepore, Oxoid, Sartorius, and Selectron. Standard membrane filter (MF) procedures and m-Staphylococcus broth were used in the evaluation. Analysis of the results was performed by comparing filter recoveries to the standard plate count using the t-test and the coefficient of variation. The data revealed that recovery on Nuclepore filters was consistently lower than the other brands and showed a wider degree of variation from the mean. All organisms recovered from the pool were gram-positive cocci, and the colonies ranged from white to yellow-gold in color. Approximately 15% of both the white and yellow-gold colonies were coagulase-positive, indicating that colony color alone does not denote the presence of coagulase-positive S. aureus. Since there was no correlation between colony color of the organisms recovered on membrane filters and the presence of coagulase, the feasibility of coagulase testing only the yellow-gold colonies for bathing water analysis is questionable. PMID:1236623

  9. Comparison of the BBL CHROMagar Staph aureus Agar Medium to Conventional Media for Detection of Staphylococcus aureus in Respiratory Samples

    PubMed Central

    Flayhart, Diane; Lema, Clara; Borek, Anita; Carroll, Karen C.

    2004-01-01

    Screening for Staphylococcus aureus has become routine in certain patient populations. This study is the first clinical evaluation of the BBL CHROMagar Staph aureus agar (CSA) medium (BD Diagnostics, Sparks, Md.) for detection of S. aureus in nasal surveillance cultures and in respiratory samples from cystic fibrosis (CF) patients. S. aureus colonies appear mauve on CSA. Other organisms are inhibited or produce a distinctly different colony color. S. aureus was identified from all media by slide coagulase, exogenous DNase, and mannitol fermentation assays. Susceptibility testing was performed using the agar dilution method. A total of 679 samples were evaluated. All samples were inoculated onto CSA. Nasal surveillance cultures were inoculated onto sheep blood agar (SBA) (BD Diagnostics), and samples from CF patients were inoculated onto mannitol salt agar (MSA) (BD Diagnostics). Of the 679 samples cultured, 200 organisms produced a mauve color on CSA (suspicious for S. aureus) and 180 were positive for S. aureus on SBA or MSA. Of 200 CSA-positive samples 191 were identified as S. aureus. Nine mauve colonies were slide coagulase negative and were subsequently identified as Staphylococcus lugdunensis (one), Staphylococcus epidermidis (three), Staphylococcus haemolyticus (one), and Corynebacterium species (four). CSA improved the ability to detect S. aureus by recovering 12 S. aureus isolates missed by conventional media. Of the 192 S. aureus isolates recovered, 122 were methicillin susceptible and 70 were methicillin resistant. Overall, the sensitivity and specificity of CSA in this study were 99.5 and 98%, respectively. There was no difference in the performance of the slide coagulase test or in susceptibility testing performed on S. aureus recovered from CSA compared to SBA or MSA. Our data support the use of CSA in place of standard culture media for detection of S. aureus in heavily contaminated respiratory samples. PMID:15297498

  10. Staphylococcal Enterotoxin B–Specific Monoclonal Antibody 20B1 Successfully Treats Diverse Staphylococcus aureus Infections

    PubMed Central

    Varshney, Avanish K.; Wang, Xiaobo; Scharff, Matthew D.; MacIntyre, Jennifer; Zollner, Richard S.; Kovalenko, Oleg V.; Martinez, Luis R.; Byrne, Fergus R.; Fries, Bettina C.

    2013-01-01

    Background. Methicillin-resistant Staphylococcus aureus (MRSA) has become a major health threat in the United States. Staphylococcal enterotoxin B (SEB) is a potent superantigen that contributes to its virulence. High mortality and frequent failure of therapy despite available antibiotics have stimulated research efforts to develop adjunctive therapies. Methods. Treatment benefits of SEB-specific monoclonal antibody (mAb) 20B1 were investigated in mice in sepsis, superficial skin, and deep-tissue infection models. Results. Mice challenged with a SEB-producing MRSA strain developed fatal sepsis, extensive tissue skin infection, and abscess-forming deep-seeded thigh muscle infection. Animals preimmunized against SEB or treated passively with mAb 20B1 exhibited enhanced survival in the sepsis model, whereas decrease of bacterial burden was observed in the superficial skin and deep-tissue models. mAb 20B1 bound to SEB in the infected tissue and decreased abscess formation and proinflammatory cytokine levels, lymphocyte proliferation, and neutrophil recruitment. Conclusions. mAb 20B1, an SEB-neutralizing mAb, is effective against MRSA infection. mAb 20B1 protects against lethal sepsis and reduces skin tissue invasion and deep-abscess formation. The mAb penetrates well into the abscess and binds to SEB. It affects the outcome of S. aureus infection by modulating the host's proinflammatory immune response. PMID:23922375

  11. Staphylococcus aureus Clumping Factor A Remains a Viable Vaccine Target for Prevention of S. aureus Infection

    PubMed Central

    Scully, Ingrid L.; Buurman, Ed T.; Eiden, Joseph; Jansen, Kathrin U.

    2016-01-01

    ABSTRACT In a recent article, X. Li et al. [mBio 7(1):e02232-15, 2016, http://dx.doi.org/10.1128/mBio.02232-15] investigate the utility of a vaccine composed of the Staphylococcus aureus protein clumping factor A (ClfA) in protecting mice from S. aureus infection. ClfA, one of the first proteins to be identified as a potential vaccine antigen for S. aureus prophylaxis, is currently a component of several investigational vaccines. The authors conclude that ClfA may not be effective for S. aureus prophylaxis. In contrast, previously published papers reporting positive data suggested that ClfA was potentially an important vaccine target to prevent invasive S. aureus disease. This commentary addresses the observed differences between the findings of Li et al. and those from other publications, highlighting the importance for preclinical vaccine antigen assessments to reflect the biological role of said antigen in virulence and, consequently, the importance of choosing appropriate preclinical disease models to test such antigens. PMID:26956591

  12. Chloride anion transporters inhibit growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro.

    PubMed

    Share, Andrew I; Patel, Khushali; Nativi, Cristina; Cho, Eun J; Francesconi, Oscar; Busschaert, Nathalie; Gale, Philip A; Roelens, Stefano; Sessler, Jonathan L

    2016-06-18

    A series of aminopyrrolic receptors were tested as anion transporters using POPC liposome model membranes. Many were found to be effective Cl(-) transporters and to inhibit clinical strains of Staphylococcus aureus growth in vitro. The best transporters proved effective against the methicillin-resistant Staphylococcus aureus (MRSA) strains, Mu50 and HP1173. Tris-thiourea tren-based chloride transporters were also shown to inhibit the growth of S. aureus in vitro. PMID:27223254

  13. Specific and cross-reacting antigens of Staphylococcus aureus of human and canine origins.

    PubMed Central

    Live, I

    1985-01-01

    Biotype -specificity of Staphylococcus aureus of human and canine origins has been found to be associated with thermolabile agglutinogens represented in S. aureus strains 17 and 61218, respectively. Both strains also have exhibited a common thermostable antigen. On that basis, absorbed antisera have been developed for the differentiation of S. aureus of the two biotypes. In the present study, still another thermostable agglutinogen was established, shared by strain 17 and some S. aureus strains of canine origin, as represented by S. aureus strain 887. These findings led to modification and enhanced specificity of the serological method of distinguishing S. aureus of the human biotype from S. aureus of the canine biotype. PMID:2578480

  14. Efficacy of two barrier teat dips containing chlorous acid germicides against experimental challenge with Staphylococcus aureus and Streptococcus agalactiae.

    PubMed

    Boddie, R L; Nickerson, S C; Kemp, G K

    1994-10-01

    Two postmilking teat dips were tested for efficacy against Staphylococcus aureus and Streptococcus agalactiae using experimental challenge procedures recommended by the National Mastitis Council. Both dips contained chlorous acid as the primary germicidal agent and lactic acid or mandelic acid as the chlorous acid activator. The dip activated with mandelic acid significantly reduced new IMI by Staph. aureus and Strep. agalactiae. The IMI rate was reduced 68.7% for Staph. aureus and 56.4% for Strep. agalactiae. The dip activated with lactic acid significantly reduced new Staph. aureus IMI by 69.3% but did not significantly reduce new Strep. agalactiae IMI (35.2% reduction) through the full 11-wk study period. Teat skin condition did not change from pretrial status after using either teat dip during the study. PMID:7836608

  15. Novel Staphylococcus aureus Secreted Protein Alters Keratinocyte Proliferation and Elicits a Proinflammatory Response In Vitro and In Vivo.

    PubMed

    Merriman, Joseph A; Klingelhutz, Aloysius J; Diekema, Daniel J; Leung, Donald Y M; Schlievert, Patrick M

    2015-08-11

    Staphylococcus aureus is a leading cause of surgical site infections that results in increased hospital stays due to the development of chronic wounds. Little is known about factors involved in S. aureus' ability to prevent wounds from healing. We discovered a novel secreted protein produced by a surgical site isolate of S. aureus that prevents keratinocyte proliferation. The protein has a molecular weight of 15.7 kDa and an isoelectric point of 8.9. The cloned and purified protein has cytotoxic and proinflammatory properties, as shown in vitro and in vivo. Potent biological effects on keratinocytes and rabbit skin suggest that this protein may play an important role in preventing re-epithelialization. Its lack of homology to known exotoxins suggests that this protein is novel, and this observation is likely to open a new field of research in S. aureus exotoxins. Due to its cytotoxic activities, we call this new protein ε-cytotoxin. PMID:26177220

  16. Genome Sequences of Four Staphylococcus aureus Strains Isolated from Bovine Mastitis.

    PubMed

    Kant, Ravi; Taponen, Suvi; Koort, Joanna; Paulin, Lars; Åvall-Jääskeläinen, Silja; Palva, Airi

    2015-01-01

    Staphylococcus aureus is a major causative agent of mastitis in dairy cows. The pathogenicity of S. aureus may vary; it is able to cause severe clinical mastitis, but most often it is associated with chronic subclinical mastitis. Here, we present the genome assemblies of four S. aureus strains from bovine mastitis. PMID:25908141

  17. Phenotypic and genotypic antimicrobial resistance traits of foodborne Staphylococcus aureus isolates from Shanghai

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Staphylococcus aureus is a recognized pathogen in humans, which causes nosocomial infections and food poisoning. The transmission of antibiotic resistant S. aureus (ARSA), especially methicillin-resistant S. aureus (MRSA), between food products and humans has become a serious problem. Hence, it is n...

  18. Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host-Pathogen Interactions.

    PubMed

    Crosby, H A; Kwiecinski, J; Horswill, A R

    2016-01-01

    The human commensal bacterium Staphylococcus aureus can cause a wide range of infections ranging from skin and soft tissue infections to invasive diseases like septicemia, endocarditis, and pneumonia. Muticellular organization almost certainly contributes to S. aureus pathogenesis mechanisms. While there has been considerable focus on biofilm formation and its role in colonizing prosthetic joints and indwelling devices, less attention has been paid to nonsurface-attached group behavior like aggregation and clumping. S. aureus is unique in its ability to coagulate blood, and it also produces multiple fibrinogen-binding proteins that facilitate clumping. Formation of clumps, which are large, tightly packed groups of cells held together by fibrin(ogen), has been demonstrated to be important for S. aureus virulence and immune evasion. Clumps of cells are able to avoid detection by the host's immune system due to a fibrin(ogen) coat that acts as a shield, and the size of the clumps facilitates evasion of phagocytosis. In addition, clumping could be an important early step in establishing infections that involve tight clusters of cells embedded in host matrix proteins, such as soft tissue abscesses and endocarditis. In this review, we discuss clumping mechanisms and regulation, as well as what is known about how clumping contributes to immune evasion. PMID:27565579

  19. Synergism between Medihoney and rifampicin against methicillin-resistant Staphylococcus aureus (MRSA).

    PubMed

    Müller, Patrick; Alber, Dagmar G; Turnbull, Lynne; Schlothauer, Ralf C; Carter, Dee A; Whitchurch, Cynthia B; Harry, Elizabeth J

    2013-01-01

    Skin and chronic wound infections caused by highly antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are an increasing and urgent health problem worldwide, particularly with sharp increases in obesity and diabetes. New Zealand manuka honey has potent broad-spectrum antimicrobial activity, has been shown to inhibit the growth of MRSA strains, and bacteria resistant to this honey have not been obtainable in the laboratory. Combinational treatment of chronic wounds with manuka honey and common antibiotics may offer a wide range of advantages including synergistic enhancement of the antibacterial activity, reduction of the effective dose of the antibiotic, and reduction of the risk of antibiotic resistance. The aim of this study was to investigate the effect of Medihoney in combination with the widely used antibiotic rifampicin on S. aureus. Using checkerboard microdilution assays, time-kill curve experiments and agar diffusion assays, we show a synergism between Medihoney and rifampicin against MRSA and clinical isolates of S. aureus. Furthermore, the Medihoney/rifampicin combination stopped the appearance of rifampicin-resistant S. aureus in vitro. Methylglyoxal (MGO), believed to be the major antibacterial compound in manuka honey, did not act synergistically with rifampicin and is therefore not the sole factor responsible for the synergistic effect of manuka honey with rifampicin. Our findings support the idea that a combination of honey and antibiotics may be an effective new antimicrobial therapy for chronic wound infections. PMID:23469049

  20. Subpopulations of Staphylococcus aureus clonal complex 121 are associated with distinct clinical entities.

    PubMed

    Kurt, Kevin; Rasigade, Jean-Philippe; Laurent, Frederic; Goering, Richard V; Žemličková, Helena; Machova, Ivana; Struelens, Marc J; Zautner, Andreas E; Holtfreter, Silva; Bröker, Barbara; Ritchie, Stephen; Reaksmey, Sin; Limmathurotsakul, Direk; Peacock, Sharon J; Cuny, Christiane; Layer, Franziska; Witte, Wolfgang; Nübel, Ulrich

    2013-01-01

    We investigated the population structure of Staphylococcus aureus clonal complex CC121 by mutation discovery at 115 genetic housekeeping loci from each of 154 isolates, sampled on five continents between 1953 and 2009. In addition, we pyro-sequenced the genomes from ten representative isolates. The genome-wide SNPs that were ascertained revealed the evolutionary history of CC121, indicating at least six major clades (A to F) within the clonal complex and dating its most recent common ancestor to the pre-antibiotic era. The toxin gene complement of CC121 isolates was correlated with their SNP-based phylogeny. Moreover, we found a highly significant association of clinical phenotypes with phylogenetic affiliations, which is unusual for S. aureus. All isolates evidently sampled from superficial infections (including staphylococcal scalded skin syndrome, bullous impetigo, exfoliative dermatitis, conjunctivitis) clustered in clade F, which included the European epidemic fusidic-acid resistant impetigo clone (EEFIC). In comparison, isolates from deep-seated infections (abscess, furuncle, pyomyositis, necrotizing pneumonia) were disseminated in several clades, but not in clade F. Our results demonstrate that phylogenetic lineages with distinct clinical properties exist within an S. aureus clonal complex, and that SNPs serve as powerful discriminatory markers, able to identify these lineages. All CC121 genomes harboured a 41-kilobase prophage that was dissimilar to S. aureus phages sequenced previously. Community-associated MRSA and MSSA from Cambodia were extremely closely related, suggesting this MRSA arose in the region. PMID:23505464

  1. Subpopulations of Staphylococcus aureus Clonal Complex 121 Are Associated with Distinct Clinical Entities

    PubMed Central

    Kurt, Kevin; Rasigade, Jean-Philippe; Laurent, Frederic; Goering, Richard V.; Žemličková, Helena; Machova, Ivana; Struelens, Marc J.; Zautner, Andreas E.; Holtfreter, Silva; Bröker, Barbara; Ritchie, Stephen; Reaksmey, Sin; Limmathurotsakul, Direk; Peacock, Sharon J.; Cuny, Christiane; Layer, Franziska; Witte, Wolfgang; Nübel, Ulrich

    2013-01-01

    We investigated the population structure of Staphylococcus aureus clonal complex CC121 by mutation discovery at 115 genetic housekeeping loci from each of 154 isolates, sampled on five continents between 1953 and 2009. In addition, we pyro-sequenced the genomes from ten representative isolates. The genome-wide SNPs that were ascertained revealed the evolutionary history of CC121, indicating at least six major clades (A to F) within the clonal complex and dating its most recent common ancestor to the pre-antibiotic era. The toxin gene complement of CC121 isolates was correlated with their SNP-based phylogeny. Moreover, we found a highly significant association of clinical phenotypes with phylogenetic affiliations, which is unusual for S. aureus. All isolates evidently sampled from superficial infections (including staphylococcal scalded skin syndrome, bullous impetigo, exfoliative dermatitis, conjunctivitis) clustered in clade F, which included the European epidemic fusidic-acid resistant impetigo clone (EEFIC). In comparison, isolates from deep-seated infections (abscess, furuncle, pyomyositis, necrotizing pneumonia) were disseminated in several clades, but not in clade F. Our results demonstrate that phylogenetic lineages with distinct clinical properties exist within an S. aureus clonal complex, and that SNPs serve as powerful discriminatory markers, able to identify these lineages. All CC121 genomes harboured a 41-kilobase prophage that was dissimilar to S. aureus phages sequenced previously. Community-associated MRSA and MSSA from Cambodia were extremely closely related, suggesting this MRSA arose in the region. PMID:23505464

  2. Staphylococcus aureus nasopharyngeal carriage in rural and urban northern Vietnam

    PubMed Central

    Van Nguyen, Kinh; Zhang, Tianying; Thi Vu, Bich Ngoc; Dao, Trinh Tuyet; Tran, Toan Khanh; Thi Nguyen, Diep Ngoc; Thi Tran, Huong Kieu; Thi Nguyen, Chuc Kim; Fox, Annette; Horby, Peter; Wertheim, Heiman

    2014-01-01

    Background Staphylococcus aureus is a common human pathogen that can colonise the respiratory tract and cause infection. Here we investigate the risk factors associated with nasopharyngeal carriage of S. aureus (including methicillin-resistant S. aureus [MRSA]) in Vietnam. Methods Between February and June 2012, nasal and pharyngeal swabs for S. aureus culture, and demographic and socioeconomic data were taken from 1016 participants in urban and rural northern Vietnam, who were randomly selected from pre-specified age strata. Results Overall S. aureus prevalence was 303/1016 (29.8%; adjusted for age: 33.8%). Carriage in the main cohort was found to be associated with younger age (≤5 years [OR 3.13, CI 1.62–6.03]; 6–12 [OR 6.87, CI 3.95–11.94]; 13–19 [OR 6.47, CI 3.56–11.74]; 20–29 [OR 4.73, CI 2.40–9.31]; 30–59 [OR 1.74, CI 1.04–2.92); with ≥60 as reference), living in an urban area (OR 1.36, CI 1.01–1.83) and antibiotics use (OR 0.69, CI 0.49–0.96). MRSA was detected in 80/1016 (7.9%). Being aged ≤5 years (OR 4.84, CI 1.47–15.97); 6–12 (OR 10.21, CI 3.54–29.50); 20–29 (OR 4.01, CI 1.09–14.77) and wealth (>3/5 wealth index, OR 1.63 CI 1.01–2.62) were significant risk factors for MRSA carriage. Conclusions Nasopharyngeal carriage of S. aureus is present in one-third of the Vietnamese population, and is more prevalent among children. Pharyngeal carriage is more common than nasal carriage. Risk factors for S. aureus (including MRSA) carriage are identified in the community. PMID:25187670

  3. Investigational drugs to treat methicillin-resistant Staphylococcus aureus

    PubMed Central

    Vuong, Cuong; Yeh, Anthony J; Cheung, Gordon YC; Otto, Michael

    2016-01-01

    Introduction Staphylococcus aureus remains one of the leading causes of morbidity and mortality worldwide. This is to a large extent due to antibiotic-resistant strains, in particular methicillin-resistant S. aureus (MRSA). While the toll of invasive MRSA infections appears to decrease in U.S. hospitals, the rate of community-associated MRSA infections remains constant and there is a surge of MRSA in many other countries. This situation calls for continuing if not increased efforts to find novel strategies to combat MRSA infections. Areas covered This review will provide an overview of current investigational antibiotics in clinical development (up to phase II), and of therapeutic antibodies and alternative drugs against S. aureus in preclinical and clinical development, including a short description of the mechanism of action and a presentation of microbiological and clinical data. Expert opinion Increased recent antibiotic development efforts and results from pathogenesis research have led to several new antibiotics and alternative drugs, as well as a more informed selection of targets for vaccination efforts against MRSA. This developing portfolio of novel anti-staphylococcal drugs will hopefully provide us with additional and more efficient ways to combat MRSA infections in the near future and prevent us from running out of treatment options, even if new resistances arise. PMID:26536498

  4. Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives

    PubMed Central

    de Araújo, Rodrigo Santos Aquino; Barbosa-Filho, José Maria; Scotti, Marcus Tullius; Scotti, Luciana; da Cruz, Ryldene Marques Duarte; Falcão-Silva, Vivyanne dos Santos; de Siqueira-Júnior, José Pinto; Mendonça-Junior, Francisco Jaime Bezerra

    2016-01-01

    Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low Ebinding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus. PMID:27200211

  5. Staphylococcus aureus CodY Negatively Regulates Virulence Gene Expression▿

    PubMed Central

    Majerczyk, Charlotte D.; Sadykov, Marat R.; Luong, Thanh T.; Lee, Chia; Somerville, Greg A.; Sonenshein, Abraham L.

    2008-01-01

    CodY is a global regulatory protein that was first discovered in Bacillus subtilis, where it couples gene expression to changes in the pools of critical metabolites through its activation by GTP and branched-chain amino acids. Homologs of CodY can be found encoded in the genomes of nearly all low-G+C gram-positive bacteria, including Staphylococcus aureus. The introduction of a codY-null mutation into two S. aureus clinical isolates, SA564 and UAMS-1, through allelic replacement, resulted in the overexpression of several virulence genes. The mutant strains had higher levels of hemolytic activity toward rabbit erythrocytes in their culture fluid, produced more polysaccharide intercellular adhesin (PIA), and formed more robust biofilms than did their isogenic parent strains. These phenotypes were associated with derepressed levels of RNA for the hemolytic alpha-toxin (hla), the accessory gene regulator (agr) (RNAII and RNAIII/hld), and the operon responsible for the production of PIA (icaADBC). These data suggest that CodY represses, either directly or indirectly, the synthesis of a number of virulence factors of S. aureus. PMID:18156263

  6. Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power

    PubMed Central

    de Lencastre, Herminia; Oliveira, Duarte; Tomasz, Alexander

    2009-01-01

    Summary Nothing documents better the spectacular adaptive capacity of Staphylococcus aureus than the response of this important human and animal pathogen to the introduction of antimicrobial agents into the clinical environment. The effectiveness of penicillin introduced in the early 1940s was virtually annulled within a decade due to the plasmid epidemics that spread the ß-lactamase gene through the entire species of S. aureus. In 1960 within one to two years of the introduction of penicillinase resistant ß-lactams (methicillin), methicillin resistant S. aureus (MRSA) strains were identified in clinical specimens. By the 1980s, epidemic clones of MRSA acquired multidrug resistant traits and spread worldwide to become one of the most important causative agents of hospital acquired infections. In the early 2000s, MRSA strains carrying the Tn1546 transposon-based enterococcal vancomycin resistant mechanism were identified in clinical specimens, bringing the specter of a totally resistant bacterial pathogen closer to reality. Then, in the late 1990s, just as effective hygienic and antibiotic use policies managed to bring down the frequency of MRSA in hospitals of several countries, MRSA strains began to show up in the community. PMID:17921044

  7. Global regulation of Staphylococcus aureus genes by Rot.

    PubMed

    Saïd-Salim, B; Dunman, P M; McAleese, F M; Macapagal, D; Murphy, E; McNamara, P J; Arvidson, S; Foster, T J; Projan, S J; Kreiswirth, B N

    2003-01-01

    Staphylococcus aureus produces a wide array of cell surface and extracellular proteins involved in virulence. Expression of these virulence factors is tightly controlled by numerous regulatory loci, including agr, sar, sigB, sae, and arl, as well as by a number of proteins with homology to SarA. Rot (repressor of toxins), a SarA homologue, was previously identified in a library of transposon-induced mutants created in an agr-negative strain by screening for restored protease and alpha-toxin. To date, all of the SarA homologues have been shown to act as global regulators of virulence genes. Therefore, we investigated the extent of transcriptional regulation of staphylococcal genes by Rot. We compared the transcriptional profile of a rot agr double mutant to that of its agr parental strain by using custom-made Affymetrix GeneChips. Our findings indicate that Rot is not only a repressor but a global regulator with both positive and negative effects on the expression of S. aureus genes. Our data also indicate that Rot and agr have opposing effects on select target genes. These results provide further insight into the role of Rot in the regulatory cascade of S. aureus virulence gene expression. PMID:12511508

  8. Novel antibiotics for the treatment of Staphylococcus aureus.

    PubMed

    Ohlsen, Knut

    2009-11-01

    Staphylococcus aureus is a leading cause of nosocomial and community-acquired infection associated with significant morbidity and mortality. Antibiotic treatment of infections owing to S. aureus have become increasingly challenging as the pathogen has acquired a broad spectrum of antibiotic resistance mechanisms. In particular, emergence and spread of methicillin-resistant S. aureus (MRSA) progressed to a global health threat. The glycopeptides antibiotics vancomycin and teicoplanin have remained as the drugs of last resort for more than 20 years. Fortunately, in addition to the glycopeptides, several novel antibiotics including linezolid, daptomycin, tigecycline, quinupristin/dalfopristin and ceftobiprole acting against MRSA have been recently introduced into clinical practice broadening therapeutic options. Although the arsenal of antistaphylococcal drugs has filled up in recent years, the rate of MRSA infection continues to be high in most countries. This demands an ongoing search for new antibacterials and lead compounds as well as development of alternative therapies and faster diagnostics to ensure effective anti-staphylococcal therapy in the future. PMID:22112259

  9. Planktonic Aggregates of Staphylococcus aureus Protect against Common Antibiotics

    PubMed Central

    Haaber, Jakob; Cohn, Marianne Thorup; Frees, Dorte; Andersen, Thorbjørn Joest; Ingmer, Hanne

    2012-01-01

    Bacterial cells are mostly studied during planktonic growth although in their natural habitats they are often found in communities such as biofilms with dramatically different physiological properties. We have examined another type of community namely cellular aggregates observed in strains of the human pathogen Staphylococcus aureus. By laser-diffraction particle–size analysis (LDA) we show, for strains forming visible aggregates, that the aggregation starts already in the early exponential growth phase and proceeds until post-exponential phase where more than 90% of the population is part of the aggregate community. Similar to some types of biofilm, the structural component of S. aureus aggregates is the polysaccharide intercellular adhesin (PIA). Importantly, PIA production correlates with the level of aggregation whether altered through mutations or exposure to sub-inhibitory concentrations of selected antibiotics. While some properties of aggregates resemble those of biofilms including increased mutation frequency and survival during antibiotic treatment, aggregated cells displayed higher metabolic activity than planktonic cells or cells in biofilm. Thus, our data indicate that the properties of cells in aggregates differ in some aspects from those in biofilms. It is generally accepted that the biofilm life style protects pathogens against antibiotics and the hostile environment of the host. We speculate that in aggregate communities S. aureus increases its tolerance to hazardous environments and that the combination of a biofilm-like environment with mobility has substantial practical and clinical importance. PMID:22815921

  10. Factors Affecting the Persistence of Staphylococcus aureus on Fabrics

    PubMed Central

    Wilkoff, Lee J.; Westbrook, Louise; Dixon, Glen J.

    1969-01-01

    The persistence of Staphylococcus aureus (Smith) on wool blanket, wool gabardine, cotton sheeting, cotton knit jersey, cotton terry cloth, and cotton wash-and-wear fabrics was studied. The fabrics were exposed to bacterial populations by three methods: direct contact, aerosol, and a lyophilized mixture of bacteria and dust having a high content of textile fibers. The contaminated fabrics were held in 35 or 78% relative humidities at 25 C. In general, the persistence time of S. aureus populations on fabrics held in 35% relative humidity was substantially longer when the fabrics were contaminated by exposure to aerosolized cultures or to dust containing bacteria than when contaminated by direct contact. In a 78% relative humidity, bacterial populations on the fabrics persisted for substantially shorter periods of time regardless of the mode of contamination or fabric type. Cotton wash-and-wear fabric (treated with a modified triazone resin) was the material on which populations of S. aureus persisted for the shortest time. This organism retained its virulence for Swiss mice after being recovered from wool gabardine swatches held 4 weeks in 35% relative humidity and 6 weeks in 78% relative humidity. Images PMID:5775911

  11. Genomic fingerprinting of bacteriocin-producer strains of Staphylococcus aureus.

    PubMed

    Nascimento, Janaína dos S; Giambiagi-deMarval, Marcia; de Oliveira, Selma S; Ceotto, Hilana; dos Santos, Kátia Regina N; Bastos, Maria do Carmo de F

    2005-09-01

    Among 363 strains of Staphylococcus aureus, 21 were shown to produce bacteriocins (Bac), antimicrobial peptides with potential biotechnological applications. This collection includes strains which are either isolated from food, patients and healthy cattle, or are involved in subclinical bovine mastitis. From these 21 strains, 17 were shown to carry closely-related 8.0-kb Bac plasmids encoding bacteriocins either identical to or similar to aureocin A70, a bacteriocin able to inhibit strains of Listeria monocytogenes, a food-borne pathogen. Such findings prompted us to investigate the genetic relationships among these Bac+ strains. To obtain more discriminatory results, a combined analysis of AP-PCR, rep-PCR, and a modified PCR technique that we designated SD-PCR was employed. The 17 Bac+ strains harboring 8.0-kb Bac plasmids exhibited seven fingerprint patterns. One such genotype was composed of 8 out of the 11 strains associated with bovine mastitis, which suggests the prevalence of a clone of Bac+ strains involved in this animal infection carrying 8.0-kb Bac plasmids. Our data support the assumption that Bac+ strains of S. aureus carrying genetically related 8.0-kb Bac plasmids do not belong to a single clone. It seems, therefore, that 8.0-kb Bac plasmids have spread horizontally among different S. aureus strains. There also seems to be genetic diversity among the remaining Bac+ strains analyzed. PMID:16171981

  12. Persister formation in Staphylococcus aureus is associated with ATP depletion.

    PubMed

    Conlon, Brian P; Rowe, Sarah E; Gandt, Autumn Brown; Nuxoll, Austin S; Donegan, Niles P; Zalis, Eliza A; Clair, Geremy; Adkins, Joshua N; Cheung, Ambrose L; Lewis, Kim

    2016-01-01

    Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics(1). Persisters are associated with chronic infections and antibiotic treatment failure(1-3). In Escherichia coli, toxin-antitoxin modules have been linked to persister formation(4-6). The mechanism of persister formation in Gram-positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting toxin-antitoxin modules in S. aureus did not affect the level of persisters. Here, we show that S. aureus persisters are produced due to a stochastic entrance into the stationary phase accompanied by a drop in intracellular adenosine triphosphate. Cells expressing stationary-state markers are present throughout the growth phase, and increase in frequency with cell density. Cell sorting revealed that the expression of stationary markers is associated with a 100-1,000-fold increase in the likelihood of survival to antibiotic challenge. The adenosine triphosphate level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotics. PMID:27572649

  13. Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections.

    PubMed

    Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves; Felden, Brice

    2016-09-01

    Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

  14. Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections

    PubMed Central

    Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves

    2016-01-01

    Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202

  15. An investigation of exudative epidermitis (greasy pig disease) and antimicrobial resistance patterns of Staphylococcus hyicus and Staphylococcus aureus isolated from clinical cases

    PubMed Central

    Park, Jeonghwa; Friendship, Robert M.; Poljak, Zvonimir; Weese, J. Scott; Dewey, Cate E.

    2013-01-01

    Exudative epidermitis (EE) is a common skin disease of young pigs, caused mainly by Staphylococcus hyicus. Increased prevalence of EE and poor response to treatment are reported. Common strategies used by Ontario pork producers to treat pigs with EE were determined using a survey. Injection of penicillin G was reported as the most common parenteral antibiotic choice. Antimicrobial resistance patterns of S. hyicus and Staphylococcus aureus isolated from clinical cases (30 herds with samples from approximately 6 pigs per farm) showed that 97% of S. hyicus isolates were resistant to penicillin G and ampicillin; 71% of these isolates were resistant to ceftiofur. Similar resistance was noted among S. aureus isolates. Antimicrobial resistance has become a problem in the treatment of EE in Ontario. PMID:23904636

  16. Efficacy of .18% iodine teat dip against Staphylococcus aureus and Streptococcus agalactiae.

    PubMed

    Boddie, R L; Nickerson, S C

    1989-04-01

    Effective postmilking teat dip products with lower iodine concentrations are being formulated as concern increases about iodine residues in milk. Increased free iodine concentration with greater germicidal activity in teat dip products is also possible with special formulation procedures. Low iodine concentration dips are cheaper and have reduced teat irritation. A concentrated iodine teat dip containing .18% iodine and 8 ppm free iodine upon dilution was evaluated under experimental bacterial challenge to determine efficacy for prevention of new intramammary infections. The undiluted product also contained 15% collagen protein emollient as a teat skin conditioner. Efficacy of the teat dip was 93.6 and 51. 7% for Staphylococcus aureus (Newbould 305) and Streptococcus agalactiae (McDonald 44). No adverse effects of the dip on teat skin were noted. PMID:2663939

  17. Implantation of Corynebacterium pseudodiphtheriticum for elimination of Staphylococcus aureus from the nasal cavity in volunteers

    NASA Astrophysics Data System (ADS)

    Viacheslav, Ilyin; Kiryukhina, Nataliya

    Nasal carriage of Staphylococcus aureus is a well-documented risk factor of infection and inflammation of the skin, soft tissues and bacteremia. It is also known that most often etiology of these disorders is associated with autoinfection. The present-day methods of opportunistic pathogens eradication from the nasal cavity are based principally on the use of antiseptic and antibacterial agents. For instance, a local antibiotic mupirocin in the form of nasal ointment is considered to be the gold standard for the treatment of S. aureus carriage. The literature describes investigations showing how mupirocin can strengthen antibiotic resistance in S. aureus strains, including those with methicillin resistance (MRSA). It is also common knowledge that recolonization of the nasal mucous membrane takes place within several months after mupirocin treatment. This circumstance dictates the necessity to look for alternative ways of preventing the S. aureus carriage and methods of elimination. One of the methods of nasal S. aureus elimination is implantation of nonpathogenic microorganisms which will extrude opportunistic pathogens without impinging the symbiotic microbiota. Effectiveness of saline suspension of Corynebacterium pseudodiphtheriticum containing spray was assessed in a several chamber experiments with simulation of some spaceflight factors (dry immersion, isolation). Various schemes of application of preparations were applied. In all cases of corynebacteria application the strong inhibiting effect against S. aureus was detected. This fact opens a prospect of using nonpathogenic corynebacteria as a nasal probiotic. Administration of the nasal corynebacteria spray possibly prevented cross-infection by MRSA and appearance of staphylococcal infection. Further pre-clinical and clinical study of this bacterial therapy method is under development.

  18. Prevalence of Toxin Genes among the Clinical Isolates of Staphylococcus aureus and its Clinical Impact

    PubMed Central

    Deodhar, Divya; Varghese, George; Balaji, Veeraraghavan; John, James; Rebekah, Grace; Janardhanan, Jeshina; Jeyaraman, Ranjith; Jasmine, Sudha; Mathews, Prasad

    2015-01-01

    Introduction: Staphylococcus aureus (S. aureus) causes a variety of infections, ranging from a mild skin infection to blood stream infections and deep seated infections. As Stapylococcus aureus bacteremia (SAB) has the tendency to cause endovascular and metastatic infections, complications can occur at almost all sites of the body. Hence, SAB is associated with increased morbidity and mortality in spite of appropriate antimicrobial treatment. The virulence in S. aureus is determined by the presence of adhesins and toxins, which behave like superantigens (SAgs) and leads to a massive release of proinflammatory cytokines causing overwhelming inflammatory response leading to endothelial leakage, hemodynamic shock, multiorgan failure, and possibly death. Materials and Methods: One year prospective study conducted in a tertiary care hospital in southern part of India included all patients with SAB. Clinical details were filled according to. All isolates were subjected to polymerase chain reaction (PCR) for enterotoxin profiling. Results: A total of 101 patients of SAB were identified which comprises of 61 (60.4%) patients with methicillin-susceptible S. aureus (MSSA) and 40 (39.6%) patients with methicillin-resistant S. aureus (MRSA). Most common predictors of mortality were prior hospitalization and antibiotic intake, severe organ dysfunction, shock, tachycardia, and leukocytosis. Two-third of the isolates had at least one enterotoxin, most prevalent was sea; 28% and 27% (P - value = 0.001) MSSA isolates had seg and sei; whereas, 38.6% (P - value < 0.001) of MRSA isolates were found to have sea. The most common enterotoxin associated with mortality was sei, which comprised of 38% of all mortality. Conclusion: In SAB, the significant predictors of mortality were prior hospitalization and antibiotic intake, presence of multiorgan dysfunction, and shock. Although overall significance between the enterotoxin and shock could not be demonstrated, it successfully demonstrated

  19. Improving the safety of Staphylococcus aureus polyvalent phages by their production on a Staphylococcus xylosus strain.

    PubMed

    El Haddad, Lynn; Ben Abdallah, Nour; Plante, Pier-Luc; Dumaresq, Jeannot; Katsarava, Ramaz; Labrie, Steve; Corbeil, Jacques; St-Gelais, Daniel; Moineau, Sylvain

    2014-01-01

    Team1 (vB_SauM_Team1) is a polyvalent staphylococcal phage belonging to the Myoviridae family. Phage Team1 was propagated on a Staphylococcus aureus strain and a non-pathogenic Staphylococcus xylosus strain used in industrial meat fermentation. The two Team1 preparations were compared with respect to their microbiological and genomic properties. The burst sizes, latent periods, and host ranges of the two derivatives were identical as were their genome sequences. Phage Team1 has 140,903 bp of double stranded DNA encoding for 217 open reading frames and 4 tRNAs. Comparative genomic analysis revealed similarities to staphylococcal phages ISP (97%) and G1 (97%). The host range of Team1 was compared to the well-known polyvalent staphylococcal phages phi812 and K using a panel of 57 S. aureus strains collected from various sources. These bacterial strains were found to represent 18 sequence types (MLST) and 14 clonal complexes (eBURST). Altogether, the three phages propagated on S. xylosus lysed 52 out of 57 distinct strains of S. aureus. The identification of phage-insensitive strains underlines the importance of designing phage cocktails with broadly varying and overlapping host ranges. Taken altogether, our study suggests that some staphylococcal phages can be propagated on food-grade bacteria for biocontrol and safety purposes. PMID:25061757

  20. Improving the Safety of Staphylococcus aureus Polyvalent Phages by Their Production on a Staphylococcus xylosus Strain

    PubMed Central

    El Haddad, Lynn; Ben Abdallah, Nour; Plante, Pier-Luc; Dumaresq, Jeannot; Katsarava, Ramaz; Labrie, Steve; Corbeil, Jacques; St-Gelais, Daniel; Moineau, Sylvain

    2014-01-01

    Team1 (vB_SauM_Team1) is a polyvalent staphylococcal phage belonging to the Myoviridae family. Phage Team1 was propagated on a Staphylococcus aureus strain and a non-pathogenic Staphylococcus xylosus strain used in industrial meat fermentation. The two Team1 preparations were compared with respect to their microbiological and genomic properties. The burst sizes, latent periods, and host ranges of the two derivatives were identical as were their genome sequences. Phage Team1 has 140,903 bp of double stranded DNA encoding for 217 open reading frames and 4 tRNAs. Comparative genomic analysis revealed similarities to staphylococcal phages ISP (97%) and G1 (97%). The host range of Team1 was compared to the well-known polyvalent staphylococcal phages phi812 and K using a panel of 57 S. aureus strains collected from various sources. These bacterial strains were found to represent 18 sequence types (MLST) and 14 clonal complexes (eBURST). Altogether, the three phages propagated on S. xylosus lysed 52 out of 57 distinct strains of S. aureus. The identification of phage-insensitive strains underlines the importance of designing phage cocktails with broadly varying and overlapping host ranges. Taken altogether, our study suggests that some staphylococcal phages can be propagated on food-grade bacteria for biocontrol and safety purposes. PMID:25061757

  1. Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

    PubMed Central

    Yeaman, Michael R.; Filler, Scott G.; Schmidt, Clint S.; Ibrahim, Ashraf S.; Edwards, John E.; Hennessey, John P.

    2014-01-01

    Recent perspectives forecast a new paradigm for future “third generation” vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S

  2. Complement depletion aggravates Staphylococcus aureus septicaemia and septic arthritis

    PubMed Central

    Sakiniene, E; Bremell, T; Tarkowski, A

    1999-01-01

    The aim of the study was to assess the role of the complement system in Staphylococcus aureus arthritis and septicaemia. The murine model of haematogenously acquired septic arthritis was used, injecting intravenously toxic shock syndrome toxin-1 (TSST-1), producing S. aureus LS-1. Complement was depleted using cobra venom factor (CVF). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of complement depletion on the phagocytic activity of leucocytes was assessed in vivo and in vitro. Six days after inoculation of S. aureus the prevalence of arthritis in decomplemented mice was three-fold higher than that in controls (91% versus 25%). The clinical severity of arthritis at the end of the experiment, expressed as arthritic index, was 7.3 and 1.9, respectively. These findings were confirmed by histological index of synovitis as well as of cartilage and/or bone destruction being significantly higher in decomplemented mice than in controls (9.8 ± 1.7 versus 4.9 ± 1.2, P < 0.05; and 7.9 ± 1.7 versus 3.0 ± 0.9, P < 0.05, respectively). Also, the septicaemia-induced mortality was clearly higher in decomplemented mice compared with the controls. CVF treatment significantly reduced in vivo polymorphonuclear cell-dependent inflammation induced by subcutaneous injection of olive oil and mirroring the capacity of polymorphonuclear cells (PMNC) to migrate and/or extravasate. Besides, the decomplementation procedure significantly impaired phagocytic activity of peripheral blood leucocytes in vitro, since the number of phagocytes being able to ingest bacteria decreased by 50% when the cells were maintained in decomplemented serum compared with those in intact serum. The conclusion is that complement depletion aggravates the clinical course of S. aureus arthritis and septicaemia, possibly by a combination of decreased migration/extravasation of PMNC and an impairment of phagocytosis. PMID:9933426

  3. Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus.

    PubMed

    Yeaman, Michael R; Filler, Scott G; Schmidt, Clint S; Ibrahim, Ashraf S; Edwards, John E; Hennessey, John P

    2014-01-01

    Recent perspectives forecast a new paradigm for future "third generation" vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S

  4. Genetic Variation among Staphylococcus aureus Strains from Norwegian Bulk Milk

    PubMed Central

    Jørgensen, H. J.; Mørk, T.; Caugant, D. A.; Kearns, A.; Rørvik, L. M.

    2005-01-01

    Strains of Staphylococcus aureus obtained from bovine (n = 117) and caprine (n = 114) bulk milk were characterized and compared with S. aureus strains from raw-milk products (n = 27), bovine mastitis specimens (n = 9), and human blood cultures (n = 39). All isolates were typed by pulsed-field gel electrophoresis (PFGE). In addition, subsets of isolates were characterized using multilocus sequence typing (MLST), multiplex PCR (m-PCR) for genes encoding nine of the staphylococcal enterotoxins (SE), and the cloverleaf method for penicillin resistance. A variety of genotypes were observed, and greater genetic diversity was found among bovine than caprine bulk milk isolates. Certain genotypes, with a wide geographic distribution, were common to bovine and caprine bulk milk and may represent ruminant-specialized S. aureus. Isolates with genotypes indistinguishable from those of strains from ruminant mastitis were frequently found in bulk milk, and strains with genotypes indistinguishable from those from bulk milk were observed in raw-milk products. This indicates that S. aureus from infected udders may contaminate bulk milk and, subsequently, raw-milk products. Human blood culture isolates were diverse and differed from isolates from other sources. Genotyping by PFGE, MLST, and m-PCR for SE genes largely corresponded. In general, isolates with indistinguishable PFGE banding patterns had the same SE gene profile and isolates with identical SE gene profiles were placed together in PFGE clusters. Phylogenetic analyses agreed with the division of MLST sequence types into clonal complexes, and isolates within the same clonal complex had the same SE gene profile. Furthermore, isolates within PFGE clusters generally belonged to the same clonal complex. PMID:16332822

  5. Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia.

    PubMed

    Gauguet, Stefanie; D'Ortona, Samantha; Ahnger-Pier, Kathryn; Duan, Biyan; Surana, Neeraj K; Lu, Roger; Cywes-Bentley, Colette; Gadjeva, Mihaela; Shan, Qiang; Priebe, Gregory P; Pier, Gerald B

    2015-10-01

    Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22(+) TCRβ(+) cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection. PMID:26216419

  6. Bactericidal Effect of a Photoresponsive Carbon Monoxide-Releasing Nonwoven against Staphylococcus aureus Biofilms.

    PubMed

    Klinger-Strobel, Mareike; Gläser, Steve; Makarewicz, Oliwia; Wyrwa, Ralf; Weisser, Jürgen; Pletz, Mathias W; Schiller, Alexander

    2016-07-01

    Staphylococcus aureus is a leading pathogen in skin and skin structure infections, including surgical and traumatic infections that are associated with biofilm formation. Because biofilm formation is accompanied by high phenotypic resistance of the embedded bacteria, they are almost impossible to eradicate by conventional antibiotics. Therefore, alternative therapeutic strategies are of high interest. We generated nanostructured hybrid nonwovens via the electrospinning of a photoresponsive carbon monoxide (CO)-releasing molecule [CORM-1, Mn2(CO)10] and the polymer polylactide. This nonwoven showed a CO-induced antimicrobial activity that was sufficient to reduce the biofilm-embedded bacteria by 70% after photostimulation at 405 nm. The released CO increased the concentration of reactive oxygen species (ROS) in the biofilms, suggesting that in addition to inhibiting the electron transport chain, ROS might play a role in the antimicrobial activity of CORMs on S. aureus The nonwoven showed increased cytotoxicity on eukaryotic cells after longer exposure, most probably due to the released lactic acid, that might be acceptable for local and short-time treatments. Therefore, CO-releasing nonwovens might be a promising local antimicrobial therapy against biofilm-associated skin wound infections. PMID:27114272

  7. Tissue-specific Patterning of the Host Innate Immune Response by Staphylococcus aureus α-toxin

    PubMed Central

    Becker, Russell E. N.; Berube, Bryan J.; Sampedro, Georgia R.; DeDent, Andrea C.; Wardenburg, Juliane Bubeck

    2014-01-01

    Immunomodulatory cytotoxins are prominent virulence factors produced by Staphylococcus aureus, a leading cause of bacterial sepsis, skin infection, and pneumonia. S. aureus α-toxin is a pore-forming toxin that utilizes a widely-expressed receptor, ADAM10, to injure the host epithelium, endothelium, and immune cells. As each host tissue is characterized by a unique composition of resident cells and recruited immune cells, the outcome of α-toxin-mediated injury may depend on the infected tissue environment. Utilizing myeloid lineage-specific Adam10 knockout mice, we show that α-toxin exerts tissue-specific effects on innate immunity to staphylococcal infection. Loss of ADAM10 expression exacerbates skin infection, yet affords protection against lethal pneumonia. These diverse outcomes are not related to altered immune cell recruitment, but rather correlate with a defect in toxin-induced IL-1β production. Extension of these studies through analysis of ADAM10 double knockout mice affecting both the myeloid lineage and either the skin or lung epithelium highlight the prominence of toxin-induced injury to the epithelium in governing the outcome of infection. Together, these studies provide evidence of tissue specificity of pore-forming cytotoxin action in modulation of host immunity, and illustrate that the outcome of infection is a collective manifestation of all effects of the toxin within the tissue microenvironment. PMID:24820433

  8. Nostrils of healthy volunteers are independent with regard to Staphylococcus aureus carriage.

    PubMed

    Kildow, Beau J; Conradie, Johan P; Robson, Rachel L

    2012-11-01

    The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus. PMID:22915611

  9. Nostrils of Healthy Volunteers Are Independent with Regard to Staphylococcus aureus Carriage

    PubMed Central

    Kildow, Beau J.; Conradie, Johan P.

    2012-01-01

    The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus. PMID:22915611

  10. Antibacterial effect of borage (Echium amoenum) on Staphylococcus aureus.

    PubMed

    Abolhassani, Mohsen

    2004-10-01

    Borage (Echium amoenum) is a large annual plant of the Boraginaceae family, which grows in most of Europe and in northern Iran. The borage flower is used as a medicinal herb in France and other countries. Iranian borage is used in traditional medicine for infectious diseases, flu and as an anti-febrile. We tested the aqueous extract of borage dried flowers in vitro for its antibacterial activity. The extract showed concentration-dependent antibacterial activity against Staphylococcus aureus 8327. This activity was heat resistant, but the activity of freeze-dried extract gradually diminished during a 90-day period. The traditional use of Iranian borage flowers for infectious diseases and for controlling fever appears to be justified. PMID:15798815

  11. Quorum Sensing Inhibitors for Staphylococcus aureus from Italian Medicinal Plants

    PubMed Central

    Quave, Cassandra L.; Plano, Lisa R.W.; Bennett, Bradley C.

    2010-01-01

    Morbidity and mortality estimates due to methicillin-resistant Staphylococcus aureus (MRSA) infections continue to rise. Therapeutic options are limited by antibiotic resistance. Anti-pathogenic compounds, which inhibit quorum sensing (QS) pathways, may be a useful alternative to antibiotics. Staphylococcal QS is encoded by the agr locus and is responsible for the production of δ-hemolysin. Quantification of δ-hemolysin found in culture supernatants permits the analysis of agr activity at the translational, rather than transcriptional, level. We employed RP-HPLC techniques to investigate the anti-QS activity of 168 extracts from 104 Italian plants through quantification of δ-hemolysin. Extracts from three medicinal plants (Ballota nigra, Castanea sativa, and Sambucus ebulus) exhibited a dose-dependent response in the production of δ-hemolysin, indicating strong anti-QS activity in a pathogenic MRSA isolate. PMID:20645243

  12. Osmolyte transport in Staphylococcus aureus and the role in pathogenesis

    PubMed Central

    Schwan, William R; Wetzel, Keith J

    2016-01-01

    Osmolyte transport is a pivotal part of bacterial life, particularly in high salt environments. Several low and high affinity osmolyte transport systems have been identified in various bacterial species. A lot of research has centered on characterizing the osmolyte transport systems of Gram‐negative bacteria, but less has been done to characterize the same transport systems in Gram‐positive bacteria. This review will focus on the previous work that has been done to understand the osmolyte transport systems in the species Staphylococcus aureus and how these transporters may serve dual functions in allowing the bacteria to survive and grow in a variety of environments, including on the surface or within humans or other animals. PMID:27429907

  13. Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection

    PubMed Central

    Fu, Xiu-jun; Fang, Yong; Yao, Min

    2013-01-01

    Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off. PMID:23555074

  14. Preparation of Cell Wall Antigens of Staphylococcus aureus

    PubMed Central

    Kowalski, J. J.; Tipper, Donald J.; Berman, David T.

    1970-01-01

    Cell walls were prepared from Staphylococcus aureus strains Copenhagen and 263 by high-speed mixing in the presence of glass beads followed by differential centrifugation. Insoluble peptidoglycan complexes were derived from cell walls by extraction of teichoic acid with 10% trichloroacetic acid. Intact teichoic acid was prepared from each strain by digestion of cell walls with lysostaphin and isolated by column chromatography. Soluble glycopeptide (peptidoglycan in which only the glycan has been fragmented) and the stable complex of teichoic acid with glycopeptide were prepared by digestion of cell walls with Chalaropsis B endo-N-acetylmuramidase and were separated by column chromatography. Amino acid and amino sugar contents of walls and subunits of walls were comparable to those reported by others. Images PMID:16557799

  15. Plasmid-protein relaxation complexes in Staphylococcus aureus.

    PubMed

    Novick, R

    1976-09-01

    Protein-deoxyribonucleic acid relaxation complexes have been demonstrated for six Staphylococcus aureus plasmids out of sixteen examined. Four of these encode stretomycin resistence, have molecular weights of about 2.7 x 10(6), and are isolated as supercoiled molecules that are virtally 100% relaxable by treatment with sodium dodecyl sulfate. It is probable that these four isolates represent a single widely disseminated plasmid species. The other two plasmids showing relaxation complexes have molecular weights of about 3 x 10(6) and encode chloramphenicol resistance. The complexes in these cases are unstable, and it has not been possible to induce more than 50% relaxation by any of the standard treatments. Ten other plasmids do not show detectable complexes. These include three penicillinase plasmids, four tetracycline-resistance plasmids, one plasmid carrying kanamycin-neomycin resistance, and finally, two chloramphenicol-resistance plasmids. PMID:956124

  16. Methicillin resistant Staphylococcus aureus (MRSA) in the intensive care unit

    PubMed Central

    Haddadin, A; Fappiano, S; Lipsett, P

    2002-01-01

    Methicillin resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. MRSA strains are endemic in many American and European hospitals and account for 29%–35% of all clinical isolates. Recent studies have documented the increased costs associated with MRSA infection, as well as the importance of colonisation pressure. Surveillance strategies have been proposed especially in high risk areas such as the intensive care unit. Pneumonia and bacteraemia account for the majority of MRSA serious clinical infections, but intra-abdominal infections, osteomyelitis, toxic shock syndrome, food poisoning, and deep tissue infections are also important clinical diseases. The traditional antibiotic therapy for MRSA is a glycopeptide, vancomycin. New antibiotics have been recently released that add to the armamentarium for therapy against MRSA and include linezolid, and quinupristin/dalfopristin, but cost, side effects, and resistance may limit their long term usefulness. PMID:12151652

  17. Ceftobiprole- and ceftaroline-resistant methicillin-resistant Staphylococcus aureus.

    PubMed

    Chan, Liana C; Basuino, Li; Diep, Binh; Hamilton, Stephanie; Chatterjee, Som S; Chambers, Henry F

    2015-05-01

    The role of mecA mutations in conferring resistance to ceftobiprole and ceftaroline, cephalosporins with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity, was determined with MRSA strains COL and SF8300. The SF8300 ceftaroline-passaged mutant carried a single mecA mutation, E447K (E-to-K change at position 447), and expressed low-level resistance. This mutation in COL conferred high-level resistance to ceftobiprole but only low-level resistance to ceftaroline. The COL ceftaroline-passaged mutant, which expressed high-level resistance to ceftobiprole and ceftaroline, had mutations in pbp2, pbp4, and gdpP but not mecA. PMID:25753637

  18. Transformation analysis of three linkage groups in Staphylococcus aureus.

    PubMed Central

    Pattee, P A; Neveln, D S

    1975-01-01

    While studying a set of multiply marked mutants of Staphylococcus aureus strain 8325 by transformation, several instances of apparent genetic linkage were encountered. After showing that these linked transformations were readily inactivated by shearing of the deoxyribonucleic acid (DNA) but were resistant to dilution of the DNA, and showing that mixtures of DNA failed to form double transformants, it was concluded that the linkages were legitimate rather than the result of congression. Three linkage groups were defined: thy-101-lys-115-trp-103-thr-106, pyr-141-hisGb15-nov-pur-102, and pur-110-ilv-129. The positions of the previously studied trp and his operons corresponded to the trp-103 and hisGb15 loci. The ilv-129 position adjacent to pur-110 probably corresponds to the ilv-leu gene cluster. The distance over which linkage was detected was greater by transformation than by generalized transduction. PMID:1176430

  19. Colonization of Cimex lectularius with methicillin-resistant Staphylococcus aureus.

    PubMed

    Barbarin, Alexis M; Hu, Baofeng; Nachamkin, Irving; Levy, Michael Z

    2014-05-01

    A recent paper published by Lowe and Romney in Emerging Infectious Diseases titled, Bed bugs as Vectors for Drug-Resistant Bacteria has sparked a renewed interest in bed bug vector potential. We followed a pyrethroid resistant strain of the human bed bug (Cimex lectularius, L.) fed either human blood or human blood with added methicillin resistant Staphylococcus aureus (MRSA) for 9 days post-feeding. Results indicated that while the bed bug midgut is a hospitable environment for MRSA, the bacteria does not survive longer than 9 days within the midgut. Additionally, MRSA is not amplified within the midgut of the bug as the infection was cleared within 9 days. Due to the weekly feeding behaviours of bed bugs, these results suggest that bed bug transmission of MRSA is highly unlikely. PMID:24589308

  20. Catalase and enumeration of stressed Staphylococcus aureus cells.

    PubMed Central

    Flowers, R S; Martin, S E; Brewer, D G; Ordal, Z J

    1977-01-01

    The effects of catalase on the enumeration of stressed (heated, reduced water activity, or freeze-dried) Staphylococcus aureus cells on several selective media were examined. The addition of catalase greatly increased the enumeration of stressed cells. The beneficial effects of catalase were most pronounced on those media least efficient in enumeration of stressed staphylococci, showing increases in enumeration of up to 1,100-fold. The effects of catalase appear to be due to the reduced ability of stressed cells to repair and form colonies in the absence of an exogenous decomposer of H2O2. Thermally stressed cells were more sensitive to H2O2 than unstressed cells. During recovery, stressed cells overcame the requirement for catalase. These findings implicate H2O2 as a factor in the failure of certain selective media to adequately enumerate stressed cells and demonstrate that the addition of catalase to these media markedly increases their productivity. PMID:879771

  1. Personal Hygiene and Methicillin-resistant Staphylococcus aureus Infection

    PubMed Central

    Lin, Mei; Wolkoff, Barbara; Dodson, Douglas; Gladbach, Stephen; Zhu, Bao-Ping

    2006-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections outside the healthcare setting are an increasing concern. We conducted a case-control study to investigate an MRSA outbreak during 2002–2003 in a Missouri prison and focused on hygiene factors. Information on sociodemographic characteristics, medical history, and hygiene practices of study participants was collected by interview and medical record review. Logistic regression was used to evaluate MRSA infection in relation to hygiene factors individually and as a composite hygiene score; potential confounding factors were controlled. Selected MRSA isolates were analyzed by pulsed-field gel electrophoresis (PFGE). MRSA infection was significantly associated with a low composite hygiene score. Transmission among prison inmates appeared to be responsible for this outbreak. PFGE analysis showed that isolates were indistinguishable and associated with community-onset MRSA infections in other US prisons. Improving hygiene practices and environmental conditions may help prevent and interrupt future MRSA outbreaks in prison settings. PMID:16704779

  2. [Clonal eosinophilia revealed by recurrent Staphylococcus aureus infection].

    PubMed

    Vandenbos, F; Figueredo, M; Dumon-Gubeno, M-C; Nicolle, I; Tarhini, A; Medioni, L-D; Naman, H; Mouroux, J

    2011-06-01

    Acquired eosinophilia is currently classified into secondary (reactional to underlying diseases), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories. We report the case of a 47-year-old male who was admitted to the hospital for Staphylococcus aureus recurring infections. An hypereosinophilia was discovered and led to molecular analysis. The identification of FIP1L1-PDGFRA fusion gene permitted the diagnostic of clonal eosinophilia. Treatment by imatinib mesylate induced an haematological remission, the control of the infection and thoracotomy cicatrization. This case is original because of its infectious presentation and the efficacy of imatinib mesylate to control the infectious process. PMID:21665081

  3. Antimicrobial susceptibility of Staphylococcus aureus and characterization of methicillin-resistant Staphylococcus aureus isolated from bovine mastitis in Korea.

    PubMed

    Nam, Hyang-Mi; Lee, Ae-Li; Jung, Suk-Chan; Kim, Mal-Nam; Jang, Geum-Chan; Wee, Sung-Hwan; Lim, Suk-Kyung

    2011-02-01

    A total of 402 Staphylococcus aureus isolates from bovine mastitis milk collected during 2003-2009 in Korea were tested for susceptibility to 20 antimicrobial agents. All S. aureus isolates were susceptible to 11 of 20 antimicrobials tested; no resistance was observed against pirlimycin, telithromycin, novobiocin, penicillin/novobiocin, quinupristin/dalfopristin, clindamycin, rifampin, ciprofloxacin, trimethprim/sulfamethoxazol, vancomycin, and linezolid. Over 66% of the S. aureus isolates were resistant to penicillin. Resistance was also seen for gentamicin (11.9%), erythromycin (7.7%), methicillin (oxacillin and cefoxitin, 6.2%), and tetracycline (4.2%). No noticeable change was observed in penicillin, gentamicin, and erythromycin resistance over the 7-year period. Tetracycline resistance appeared to decrease consistently, whereas methicillin resistance was observed from 2005. About 2.7% (11/402) were resistant to three or more antimicrobials. Genotyping of the 17 methicillin-resistant S. aureus (MRSA) isolated from each cow revealed two staphylococcal cassette chromosome mec (SCCmec) types (IV and IVa), three spa types (t286, t324, and untypable), and two sequence types (ST1 and ST72). Eleven of 17 (64.7%) MRSA strains belonged to SCCmec IVa-t324-ST72. The rest of strains belonged to SCCmec IVa-t286-ST1 (n = 3) and SCCmec IV-untypable-ST72 (n = 3). None of the MRSA carried the Panton-Valentine leukocidin gene. These characteristics are the same as those found in community-acquired (CA) MRSA strains prevalent in humans in Korea. Three pulsed-field gel electrophoresis types (A-C) were observed among the 17 MRSA strains examined, and 14 strains belonged to the same pulsed-field gel electrophoresis pattern regardless of their geographical origin and year of isolation. The results of this study provide evidence of CA-MRSA infection in dairy cattle for the first time in Korea. PMID:21034263

  4. [Severe infection by methicillin sensitive Staphylococcus aureus producing Panton-Valentine leukocidin: reports of two cases].

    PubMed

    Brizuela, Martín; Pérez, Guadalupe; Ruvinsky, Silvina; Sarkis, Claudia; Romero, Romina; Mastroianni, Alejandra; Casimir, Lidia; Venuta, María E; Gómez Bonduele, Verónica; Bologna, Rosa

    2016-08-01

    Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria. PMID:27399020

  5. Population-Based Estimates of Methicillin-Resistant "Staphylococcus aureus" (MRSA) Infections among High School Athletes--Nebraska, 2006-2008

    ERIC Educational Resources Information Center

    Buss, Bryan F.; Mueller, Shawn W.; Theis, Max; Keyser, Alison; Safranek, Thomas J.

    2009-01-01

    Methicillin-resistant "Staphylococcus aureus" (MRSA) is an emerging cause of skin and soft-tissue infections among athletes. To determine statewide incidence among high school athletes, we surveyed all 312 Nebraska high schools regarding sport programs offered, program-specific participation numbers, number of athletes with physician-diagnosed…

  6. A combination of positive dielectrophoresis driven on-line enrichment and aptamer-fluorescent silica nanoparticle label for rapid and sensitive detection of Staphylococcus aureus.

    PubMed

    Shangguan, Jingfang; Li, Yuhong; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Zou, Zhen; Shi, Hui

    2015-07-01

    Staphylococcus aureus (S. aureus) is an important human pathogen that causes several diseases ranging from superficial skin infections to life-threatening diseases. Here, a method combining positive dielectrophoresis (pDEP) driven on-line enrichment and aptamer-fluorescent silica nanoparticle label has been developed for the rapid and sensitive detection of S. aureus in microfluidic channels. An aptamer, having high affinity to S. aureus, is used as the molecular recognition tool and immobilized onto chloropropyl functionalized fluorescent silica nanoparticles through a click chemistry approach to obtain S. aureus aptamer-nanoparticle bioconjugates (Apt(S.aureus)/FNPs). The pDEP driven on-line enrichment technology was used for accumulating the Apt(S.aureus)/FNP labeled S. aureus. After incubating with S. aureus, the mixture of Apt(S.aureus)/FNP labeled S. aureus and Apt(S.aureus)/FNPs was directly introduced into the pDEP-based microfluidic system. By applying an AC voltage in a pDEP frequency region, the Apt(S.aureus)/FNP labelled S. aureus moved to the electrodes and accumulated in the electrode gap, while the free Apt(S.aureus)/FNPs flowed away. The signal that came from the Apt(S.aureus)/FNP labelled S. aureus in the focused detection areas was then detected. Profiting from the specificity of aptamer, signal amplification of FNP label and pDEP on-line enrichment, this assay can detect as low as 93 and 270 cfu mL(-1)S. aureus in deionized water and spiked water samples, respectively, with higher sensitivities than our previously reported Apt(S.aureus)/FNP based flow cytometry. Moreover, without the need for separation and washing steps usually required for FNP label involved bioassays, the total assay time including sample pretreatment was within 2 h. PMID:25963028

  7. Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2013.

    PubMed

    Coombs, Geoffrey W; Nimmo, Graeme R; Daly, Denise A; Le, Tam T; Pearson, Julie C; Tan, Hui-Leen; Robinson, James O; Collignon, Peter J; McLaws, Mary-Louise; Turnidge, John D

    2014-12-01

    From 1 January to 31 December 2013, around Australia 26 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2013 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, (with particular emphasis on susceptibility to methicillin) and to characterise the molecular epidemiology of the isolates. Overall 19.1% of the 2,010 SAB episodes were methicillin resistant, which is significantly higher than that reported in most European countries. Although the SAB 30-day all cause mortality appears to be decreasing in Australia, methicillin-resistant SAB associated mortality remains high (20.1%) and was significantly higher than methicillin-sensitive SAB associated mortality (13%) (P< 0.0001). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin sensitive S. aureus remains rare. However, in addition to the ß-lactams, approximately 50% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 20% were resistant to co-trimoxazole, tetracycline and gentamicin. Linezolid, daptomycin and teicoplanin resistance was detected in a small number of S. aureus isolates. Resistance to vancomycin was not detected. Resistance was largely attributable to 2 healthcare associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has now become the predominant healthcare associated clone in Australia. Approximately 60% of methicillin-resistant SAB were due to community associated clones. Although polyclonal, almost 50% of community associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and

  8. Nonviable Staphylococcus aureus and its peptidoglycan stimulate macrophage recruitment, angiogenesis, fibroplasia, and collagen accumulation in wounded rats.

    PubMed

    Kilcullen, J K; Ly, Q P; Chang, T H; Levenson, S M; Steinberg, J J

    1998-01-01

    We have previously shown that local application at the time of operation of Staphylococcus aureus, nonviable S. aureus, its cell wall, or S. aureus peptidoglycan accelerates wound healing. We hypothesized that this effect is due to both direct and indirect mechanisms, among which is an increase in the inflammatory response to wounding, resulting in an increase in macrophages, angiogenesis, and fibroblasts. Twenty-seven Sprague-Dawley male rats were anesthetized, and two 7-cm paravertebral skin incisions were made. Four polyvinyl alcohol sponges, two on each side, containing either 100 microliter of isotonic saline or 0.5 mg of nonviable S. aureus or S. aureus peptidoglycan in 100-microliter saline were implanted subcutaneously. Nonviable S. aureus or S. aureus peptidoglycan (860 microgram/cm incision) in 200-microliter saline were inoculated into the incisions at closure. The rats ate a commercial rat chow and drank tap water ad libitum throughout. After days 3 and 7 postwounding, rats were euthanized, and tissues were examined for immunohistochemical features of reparative tissue using ED-1, Factor VIII, and vimentin antibodies, markers for monocyte/macrophages, endothelial cells, and mesenchymal cells (including fibroblasts), respectively. Incisions treated with nonviable S. aureus or S. aureus peptidoglycan showed more macrophages along and deep in the wound tract 7 days postoperatively. Nonviable S. aureus or S. aureus peptidoglycan-treated sponges were surrounded and penetrated by much larger capsules of reparative tissue than saline-treated sponges at both 3 and 7 days. Neutrophil influx was much greater in nonviable S. aureus or S. aureus peptidoglycan-treated sponges, especially in central regions, and there were many more ED-1-stained macrophages in distinct geographic locations, specifically, the more peripheral-cortical areas. Some clustering of macrophages occurred around areas of invasion by reparative tissue into the surrounding subcutaneous fat and

  9. Glucose Augments Killing Efficiency of Daptomycin Challenged Staphylococcus aureus Persisters.

    PubMed

    Prax, Marcel; Mechler, Lukas; Weidenmaier, Christopher; Bertram, Ralph

    2016-01-01

    Treatment of Staphylococcus aureus in stationary growth phase with high doses of the antibiotic daptomycin (DAP) eradicates the vast majority of the culture and leaves persister cells behind. Despite resting in a drug-tolerant and dormant state, persister cells exhibit metabolic activity which might be exploited for their elimination. We here report that the addition of glucose to S. aureus persisters treated with DAP increased killing by up to five-fold within one hour. This glucose-DAP effect also occurred with strains less sensitive to the drug. The underlying mechanism is independent of the proton motive force and was not observed with non-metabolizable 2-deoxy-glucose. Our results are consistent with two hypotheses on the glucose-DAP interplay. The first is based upon glucose-induced carbohydrate transport proteins that may influence DAP and the second suggests that glucose may trigger the release or activity of cell-lytic proteins to augment DAP's mode of action. PMID:26960193

  10. Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice.

    PubMed

    Lambrechts, Saskia A G; Demidova, Tatiana N; Aalders, Maurice C G; Hasan, Tayyaba; Hamblin, Michael R

    2005-07-01

    The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence. PMID:15986057

  11. Multidrug Efflux Pumps in Staphylococcus aureus: an Update

    PubMed Central

    Costa, Sofia Santos; Viveiros, Miguel; Amaral, Leonard; Couto, Isabel

    2013-01-01

    The emergence of infections caused by multi- or pan-resistant bacteria in the hospital or in the community settings is an increasing health concern. Albeit there is no single resistance mechanism behind multiresistance, multidrug efflux pumps, proteins that cells use to detoxify from noxious compounds, seem to play a key role in the emergence of these multidrug resistant (MDR) bacteria. During the last decades, experimental data has established their contribution to low level resistance to antimicrobials in bacteria and their potential role in the appearance of MDR phenotypes, by the extrusion of multiple, unrelated compounds. Recent studies suggest that efflux pumps may be used by the cell as a first-line defense mechanism, avoiding the drug to reach lethal concentrations, until a stable, more efficient alteration occurs, that allows survival in the presence of that agent. In this paper we review the current knowledge on MDR efflux pumps and their intricate regulatory network in Staphylococcus aureus, a major pathogen, responsible from mild to life-threatening infections. Particular emphasis will be given to the potential role that S. aureus MDR efflux pumps, either chromosomal or plasmid-encoded, have on resistance towards different antimicrobial agents and on the selection of drug - resistant strains. We will also discuss the many questions that still remain on the role of each specific efflux pump and the need to establish appropriate methodological approaches to address all these questions. PMID:23569469

  12. Excreted Cytoplasmic Proteins Contribute to Pathogenicity in Staphylococcus aureus.

    PubMed

    Ebner, Patrick; Rinker, Janina; Nguyen, Minh Thu; Popella, Peter; Nega, Mulugeta; Luqman, Arif; Schittek, Birgit; Di Marco, Moreno; Stevanovic, Stefan; Götz, Friedrich

    2016-06-01

    Excretion of cytoplasmic proteins in pro- and eukaryotes, also referred to as "nonclassical protein export," is a well-known phenomenon. However, comparatively little is known about the role of the excreted proteins in relation to pathogenicity. Here, the impact of two excreted glycolytic enzymes, aldolase (FbaA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on pathogenicity was investigated in Staphylococcus aureus Both enzymes bound to certain host matrix proteins and enhanced adherence of the bacterial cells to host cells but caused a decrease in host cell invasion. FbaA and GAPDH also bound to the cell surfaces of staphylococcal cells by interaction with the major autolysin, Atl, that is involved in host cell internalization. Surprisingly, FbaA showed high cytotoxicity to both MonoMac 6 (MM6) and HaCaT cells, while GAPDH was cytotoxic only for MM6 cells. Finally, the contribution of external FbaA and GAPDH to S. aureus pathogenicity was confirmed in an insect infection model. PMID:27001537

  13. MOLECULAR CHARACTERIZATION OF STAPHYLOCOCCUS AUREUS STRAINS ISOLATED FROM INFECTIVE ENDOCARDITIS.

    PubMed

    Oprea, Mihaela; Patriche, David Sebastian; Străuţ, Monica; Antohe, Felicia

    2014-01-01

    Infective endocarditis (IE) is an infection of the heart endothelium and valves and is frequently a consequence of a sanguine flow turbulence and injury of endocardium. Recent studies revealed an increase of Staphylococcus aureus strains involved in IE, but no evident correlations between the genetic background of this bacterium and IE involvement of certain strains have been found yet. In this study we analyzed the virulence profile, including adhesins, exotoxins, superantigens and biofilm determinants, along with agr type detection, for S. aureus strains isolated from IE, versus non-IE originating strains. We performed also bacterial typing (SCCmec typing, spa-typing and MLST typing), in order to compare our strains with international databases repositories. Although the study was carried out on a reduced number of isolates, our observations confirm the previous works, showing that no major differences were observed between the genetic backgrounds of the two groups of strains analyzed. Notably, the added value of this study was optimization of two new multiplex PCR protocols, and the enrichment of international databases with three new spa-types, three new MLST alleles and four new MLST sequence types. PMID:26201122

  14. Expression and crystallization of DsbA from Staphylococcus aureus

    SciTech Connect

    Heras, B. Kurz, M.; Jarrott, R.; Byriel, K. A.; Jones, A.; Thöny-Meyer, L.; Martin, J. L.

    2007-11-01

    Free-interface diffusion crystallization chips were used to identify crystallization conditions for S. aureus DsbA, representing the first Gram-positive DsbA to be crystallized. Native and selenomethionine-derivative crystals diffracted to 2.1 and 2.4 Å resolution, respectively. Bacterial Dsb proteins catalyse the in vivo formation of disulfide bonds, a critical step in the stability and activity of many proteins. Most studies on Dsb proteins have focused on Gram-negative bacteria and thus the process of oxidative folding in Gram-positive bacteria is poorly understood. To help elucidate this process in Gram-positive bacteria, DsbA from Staphylococcus aureus (SaDsbA) has been focused on. Here, the expression, purification, crystallization and preliminary diffraction analysis of SaDsbA are reported. SaDsbA crystals diffract to a resolution limit of 2.1 Å and belong to the hexagonal space group P6{sub 5} or P6{sub 1}, with unit-cell parameters a = b = 72.1, c = 92.1 Å and one molecule in the asymmetric unit (64% solvent content)

  15. Haem Recognition By a Staphylococcus Aureus NEAT Domain

    SciTech Connect

    Grigg, J.C.; Vermeiren, C.; Heinrichs, D.E.; Murphy, M.E.P.

    2009-06-01

    Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains.

  16. Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus.

    PubMed

    Khodaverdian, Varandt; Pesho, Michelle; Truitt, Barbara; Bollinger, Lucy; Patel, Parita; Nithianantham, Stanley; Yu, Guanping; Delaney, Elizabeth; Jankowsky, Eckhard; Shoham, Menachem

    2013-08-01

    Antivirulence agents inhibit the production of disease-causing virulence factors but are neither bacteriostatic nor bactericidal. Antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA) strain USA300, the most widespread community-associated MRSA strain in the United States, were discovered by virtual screening against the response regulator AgrA, which acts as a transcription factor for the expression of several of the most prominent S. aureus toxins and virulence factors involved in pathogenesis. Virtual screening was followed by similarity searches in the databases of commercial vendors. The small-molecule compounds discovered inhibit the production of the toxins alpha-hemolysin and phenol-soluble modulin α in a dose-dependent manner without inhibiting bacterial growth. These antivirulence agents are small-molecule biaryl compounds in which the aromatic rings either are fused or are separated by a short linker. One of these compounds is the FDA-approved nonsteroidal anti-inflammatory drug diflunisal. This represents a new use for an old drug. Antivirulence agents might be useful in prophylaxis and as adjuvants in antibiotic therapy for MRSA infections. PMID:23689713

  17. Staphylococcus aureus infections: transmission within households and the community

    PubMed Central

    Knox, Justin; Uhlemann, Anne-Catrin; Lowy, Franklin D.

    2015-01-01

    Staphylococcus aureus , both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites including schools and daycare facilities play a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to play an important role in facilitating transmission. The integration of research tools including whole genome sequencing, mathematical modeling and social network analysis have provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus. PMID:25864883

  18. Susceptibility of Staphylococcus aureus biofilms to reactive discharge gases

    PubMed Central

    Traba, Christian; Liang, Jun F.

    2011-01-01

    Formation of bacterial biofilms at solid-liquid interfaces creates numerous problems in both industrial and biomedical sciences. In this study, the susceptibility of Staphylococcus aureus biofilms to discharge gas generated from plasma was tested. It was found that despite distinct chemical/physical properties, discharge gases from oxygen, nitrogen, and argon demonstrated very potent and almost the same anti-biofilm activity. The bacterial cells in S. aureus biofilms were killed (>99.9%) by discharge gas within minutes of exposure. Under optimal experimental conditions, no bacteria and biofilm re-growth from discharge gas treated biofilms was found. Further studies revealed that the anti-biofilm activity of the discharge gas occurred by two distinct mechanisms: 1) killing bacteria in biofilms by causing severe cell membrane damage, and 2) damaging the extracellular polymeric matrix in the architecture of the biofilm to release biofilm from the surface of the solid substratum . Information gathered from this study provides an insight into the anti-biofilm mechanisms of plasma and confirms the applications of discharge gas in the treatment of biofilms and biofilm related bacterial infections. PMID:21774615

  19. Glucose Augments Killing Efficiency of Daptomycin Challenged Staphylococcus aureus Persisters

    PubMed Central

    Prax, Marcel; Mechler, Lukas; Weidenmaier, Christopher; Bertram, Ralph

    2016-01-01

    Treatment of Staphylococcus aureus in stationary growth phase with high doses of the antibiotic daptomycin (DAP) eradicates the vast majority of the culture and leaves persister cells behind. Despite resting in a drug-tolerant and dormant state, persister cells exhibit metabolic activity which might be exploited for their elimination. We here report that the addition of glucose to S. aureus persisters treated with DAP increased killing by up to five-fold within one hour. This glucose-DAP effect also occurred with strains less sensitive to the drug. The underlying mechanism is independent of the proton motive force and was not observed with non-metabolizable 2-deoxy-glucose. Our results are consistent with two hypotheses on the glucose-DAP interplay. The first is based upon glucose-induced carbohydrate transport proteins that may influence DAP and the second suggests that glucose may trigger the release or activity of cell-lytic proteins to augment DAP’s mode of action. PMID:26960193

  20. Antimicrobial activity of essential oils against Staphylococcus aureus biofilms.

    PubMed

    Vázquez-Sánchez, Daniel; Cabo, Marta L; Rodríguez-Herrera, Juan J

    2015-12-01

    The present study was aimed to evaluate the potential of essential oils to remove the foodborne pathogen Staphylococcus aureus from food-processing facilities. The effectiveness of 19 essential oils against planktonic cells of S. aureus was firstly assessed by minimal inhibitory concentration. Planktonic cells showed a wide variability in resistance to essential oils, with thyme oil as the most effective, followed by lemongrass oil and then vetiver oil. The eight essential oils most effective against planktonic cells were subsequently tested against 48-h-old biofilms formed on stainless steel. All essential oils reduced significantly (p < 0.01) the number of viable biofilm cells, but none of them could remove biofilms completely. Thyme and patchouli oils were the most effective, but high concentrations were needed to achieve logarithmic reductions over 4 log CFU/cm(2) after 30 min exposure. Alternatively, the use of sub-lethal doses of thyme oil allowed to slow down biofilm formation and to enhance the efficiency of thyme oil and benzalkonium chloride against biofilms. However, some cellular adaptation to thyme oil was detected. Therefore, essential oil-based treatments should be based on the rotation and combination of different essential oils or with other biocides to prevent the emergence of antimicrobial-resistant strains. PMID:25280938

  1. The mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus.

    PubMed

    Lee, Young-Seob; Han, Sin-Hee; Lee, Su-Hwan; Kim, Young-Guk; Park, Chung-Berm; Kang, Ok-Hwa; Keum, Joon-Ho; Kim, Sung-Bae; Mun, Su-Hyun; Seo, Yun-Soo; Myung, Noh-Yil; Kwon, Dong-Yeul

    2012-08-01

    Tetrandrine (TET) is a bis-benzylisoquinoline alkaloid derived from the radix of Stephania tetrandra S. Moore. TET performs a wide spectrum of biological activities. The radix of S. tetrandrae has been used traditionally in Asia, including Korea, to treat congestive circulatory disorders and inflammatory diseases. The aim of this study was to examine the mechanism of antibacterial activity of tetrandrine against Staphylococcus aureus. The mechanism was investigated by studying the effects of TET in combination with detergent or membrane potential un-couplers. In addition, the direct involvement of peptidoglycan (PGN) was assessed in titration assays. TET activity against S. aureus was 125-250 μg/mL, and the minimum inhibitory concentration (MIC) of the two reference strains was 250 μg/mL. The OD(600) of each suspension treated with a combination of ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl) aminomethane (TRIS), and Triton X-100 (TX) with TET (0.25×MIC) had been reduced from 43% to 96%. Additional structure-function studies on the antibacterial activity of TET in combination with other agents may lead to the discovery of more effective antibacterial agents. PMID:22845553

  2. Converting a Staphylococcus aureus toxin into effective cyclic pseudopeptide antibiotics.

    PubMed

    Solecki, Olivia; Mosbah, Amor; Baudy Floc'h, Michèle; Felden, Brice

    2015-03-19

    Staphylococcus aureus produces peptide toxins that it uses to respond to environmental cues. We previously characterized PepA1, a peptide toxin from S. aureus, that induces lytic cell death of both bacterial and host cells. That led us to suggest that PepA1 has an antibacterial activity. Here, we demonstrate that exogenously provided PepA1 has activity against both Gram-positive and Gram-negative bacteria. We also see that PepA1 is significantly hemolytic, thus limiting its use as an antibacterial agent. To overcome these limitations, we converted PepA1 into nonhemolytic derivatives. Our most promising derivative is a cyclic heptapseudopeptide with inconsequential toxicity to human cells, enhanced stability in human sera, and sharp antibacterial activity. Mechanistically, linear and helical PepA1 derivatives form pores at the bacterial and erythrocyte surfaces, while the cyclic peptide induces bacterial envelope reorganization, with insignificant action on the erythrocytes. Our work demonstrates that bacterial toxins might be an attractive starting point for antibacterial drug development. PMID:25728268

  3. Staphylococcus aureus infections: transmission within households and the community.

    PubMed

    Knox, Justin; Uhlemann, Anne-Catrin; Lowy, Franklin D

    2015-07-01

    Staphylococcus aureus, both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites, including schools and daycare facilities, have a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to have an important role in facilitating transmission. The integration of research tools, including whole-genome sequencing (WGS), mathematical modeling, and social network analysis, has provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus. PMID:25864883

  4. Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

    PubMed Central

    Das, Sudip; Lindemann, Claudia; Young, Bernadette C.; Muller, Julius; Österreich, Babett; Ternette, Nicola; Winkler, Ann-Cathrin; Paprotka, Kerstin; Reinhardt, Richard; Allen, Elizabeth; Flaxman, Amy; Yamaguchi, Yuko; Rollier, Christine S.; van Diemen, Pauline; Blättner, Sebastian; Remmele, Christian W.; Selle, Martina; Dittrich, Marcus; Müller, Tobias; Vogel, Jörg; Ohlsen, Knut; Crook, Derrick W.; Massey, Ruth; Wilson, Daniel J.; Rudel, Thomas; Wyllie, David H.; Fraunholz, Martin J.

    2016-01-01

    Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection. PMID:27185949

  5. Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation.

    PubMed

    Das, Sudip; Lindemann, Claudia; Young, Bernadette C; Muller, Julius; Österreich, Babett; Ternette, Nicola; Winkler, Ann-Cathrin; Paprotka, Kerstin; Reinhardt, Richard; Förstner, Konrad U; Allen, Elizabeth; Flaxman, Amy; Yamaguchi, Yuko; Rollier, Christine S; van Diemen, Pauline; Blättner, Sebastian; Remmele, Christian W; Selle, Martina; Dittrich, Marcus; Müller, Tobias; Vogel, Jörg; Ohlsen, Knut; Crook, Derrick W; Massey, Ruth; Wilson, Daniel J; Rudel, Thomas; Wyllie, David H; Fraunholz, Martin J

    2016-05-31

    Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection. PMID:27185949

  6. Association of recurrent furunculosis with Panton-Valentine leukocidin and the genetic background of Staphylococcus aureus.

    PubMed

    Masiuk, Helena; Kopron, Katarzyna; Grumann, Dorothee; Goerke, Christiane; Kolata, Julia; Jursa-Kulesza, Joanna; Giedrys-Kalemba, Stefania; Bröker, Barbara M; Holtfreter, Silva

    2010-05-01

    Staphylococcus aureus is a major cause of skin and soft tissue infections, such as furuncles, carbuncles, and abscesses, but it also frequently colonizes the human skin and mucosa without causing clinical symptoms. Panton-Valentine leukocidin (PVL) is a pore-forming toxin that has been associated with soft tissue infections and necrotizing pneumonia. We have compared the genotypes, virulence gene repertoires, and phage patterns of 74 furunculosis isolates with those of 108 control strains from healthy nasal carriers. The large majority of furunculosis strains were methicillin sensitive. Clonal cluster (CC) 121 (CC121) and CC22 accounted for 70% of the furunculosis strains but for only 8% of the nasal isolates. The PVL-encoding genes luk-PV were detected in 85% of furunculosis strains, while their prevalence among colonizing S. aureus strains was below 1%. luk-PV genes were distributed over several lineages (CCs 5, 8, 22, 30, and 121 and sequence type 59). Even within the same lineages, luk-PV-positive phages characterized furunculosis strains, while their luk-PV-negative variants were frequent among nasal strains. The very tight epidemiological linkage between luk-PV and furunculosis, which could be separated from the genetic background of the S. aureus strain as well as from the gene makeup of the luk-PV-transducing phage, lends support to the notion of an important role for PVL in human furunculosis. These results make a case for the determination of luk-PV in recurrent soft tissue infections with methicillin-sensitive as well as methicillin-resistant S. aureus. PMID:20200289

  7. Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

    PubMed

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. PMID:25897961

  8. Colostrum Hexasaccharide, a Novel Staphylococcus aureus Quorum-Sensing Inhibitor

    PubMed Central

    Srivastava, A.; Deepak, D.; Singh, B. R.

    2015-01-01

    The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in Staphylococcus aureus. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase high-performance liquid chromatography evaporative light-scattering detection (RP-HPLC-ELSD), 1H and 13C nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). Antibiofilm activity of CHS against S. aureus and its possible interference with bacterial QS systems were determined. The inhibition and eradication potentials of the biofilms were studied by microscopic analyses and quantified by 96-well-microtiter-plate assays. Also, the ability of CHS to interfere in bacterial QS by degrading acyl-homoserine lactones (AHLs), one of the most studied signal molecules for Gram-negative bacteria, was evaluated. The results revealed that CHS exhibited promising inhibitory activities against QS-regulated secretion of VFs, including spreading ability, hemolysis, protease, and lipase activities, when applied at a rate of 5 mg/ml. The results of biofilm experiments indicated that CHS is a strong inhibitor of biofilm formation and also has the ability to eradicate it. The potential of CHS to interfere with bacterial QS systems was also examined by degradation of AHLs. Furthermore, it was documented that CHS decreased antibiotic resistance in S. aureus. The results thus give a lead that mare colostrum can be a promising source for isolating a next-generation antibacterial. PMID:25645850

  9. A pig model of acute Staphylococcus aureus induced pyemia

    PubMed Central

    Nielsen, Ole L; Iburg, Tine; Aalbaek, Bent; Leifsson, Páll S; Agerholm, Jørgen S; Heegaard, Peter; Boye, Mette; Simon, Sofie; Jensen, Kristine B; Christensen, Sophie; Melsen, Karin; Bak, Anne K; Backman, Elín R; Jørgensen, Mia H; Groegler, Désirée K; Jensen, Asger L; Kjelgaard-Hansen, Mads; Jensen, Henrik E

    2009-01-01

    Background Sepsis caused by Staphylococcus aureus constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with S. aureus, with the aim of mimicking human sepsis and pyemia. Methods The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological and histological examinations of different organs were performed 4, 5 or 6 h after inoculation. Results Clearance of bacteria from the blood was completed within the first 2 h in some of the pigs and the highest bacterial load was recorded in the lungs as compared to the spleen, liver and bones. This probably was a consequence of both the intravenous route of inoculation and the presence of pulmonary intravascular macrophages. Inoculation of bacteria induced formation of acute microabscesses in the lungs, spleen and liver, but not in the kidneys or bones. No generalized inflammatory response was recorded, i.e. IL-6 was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study. Conclusion This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of S. aureus isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock. PMID:19327150

  10. Mobilization of Genomic Islands of Staphylococcus aureus by Temperate Bacteriophage

    PubMed Central

    Moon, Bo Youn; Park, Joo Youn; Robinson, D. Ashley; Thomas, Jonathan C.; Park, Yong Ho; Thornton, Justin A.; Seo, Keun Seok

    2016-01-01

    The virulence of Staphylococcus aureus, in both human and animal hosts, is largely influenced by the acquisition of mobile genetic elements (MGEs). Most S. aureus strains carry a variety of MGEs, including three genomic islands (νSaα, νSaβ, νSaγ) that are diverse in virulence gene content but conserved within strain lineages. Although the mobilization of pathogenicity islands, phages and plasmids has been well studied, the mobilization of genomic islands is poorly understood. We previously demonstrated the mobilization of νSaβ by the adjacent temperate bacteriophage ϕSaBov from strain RF122. In this study, we demonstrate that ϕSaBov mediates the mobilization of νSaα and νSaγ, which are located remotely from ϕSaBov, mostly to recipient strains belonging to ST151. Phage DNA sequence analysis revealed that chromosomal DNA excision events from RF122 were highly specific to MGEs, suggesting sequence-specific DNA excision and packaging events rather than generalized transduction by a temperate phage. Disruption of the int gene in ϕSaBov did not affect phage DNA excision, packaging, and integration events. However, disruption of the terL gene completely abolished phage DNA packing events, suggesting that the primary function of temperate phage in the transfer of genomic islands is to allow for phage DNA packaging by TerL and that transducing phage particles are the actual vehicle for transfer. These results extend our understanding of the important role of bacteriophage in the horizontal transfer and evolution of genomic islands in S. aureus. PMID:26953931

  11. Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

    PubMed Central

    Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L.; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M.; Mylonakis, Eleftherios

    2015-01-01

    Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. PMID:25897961

  12. Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry*

    PubMed Central

    Gonzalez, David J.; Okumura, Cheryl Y.; Hollands, Andrew; Kersten, Roland; Akong-Moore, Kathryn; Pence, Morgan A.; Malone, Cheryl L.; Derieux, Jaclyn; Moore, Bradley S.; Horswill, Alexander R.; Dixon, Jack E.; Dorrestein, Pieter C.; Nizet, Victor

    2012-01-01

    Staphylococcus aureus causes a wide range of human disease ranging from localized skin and soft tissue infections to potentially lethal systemic infections. S. aureus has the biosynthetic ability to generate numerous virulence factors that assist in circumventing the innate immune system during disease pathogenesis. Recent studies have uncovered a set of extracellular peptides produced by community-associated methicillin-resistant S. aureus (CA-MRSA) with homology to the phenol-soluble modulins (PSMs) from Staphylococcus epidermidis. CA-MRSA PSMs contribute to skin infection and recruit and lyse neutrophils, and truncated versions of these peptides possess antimicrobial activity. In this study, novel CA-MRSA PSM derivatives were discovered by the use of microbial imaging mass spectrometry. The novel PSM derivatives are compared with their parent full-length peptides for changes in hemolytic, cytolytic, and neutrophil-stimulating activity. A potential contribution of the major S. aureus secreted protease aureolysin in processing PSMs is demonstrated. Finally, we show that PSM processing occurs in multiple CA-MRSA strains by structural confirmation of additional novel derivatives. This work demonstrates that IMS can serve as a useful tool to go beyond genome predictions and expand our understanding of the important family of small peptide virulence factors. PMID:22371493

  13. Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

    PubMed Central

    Quave, Cassandra L.; Estévez-Carmona, Miriam; Compadre, Cesar M.; Hobby, Gerren; Hendrickson, Howard; Beenken, Karen E.; Smeltzer, Mark S.

    2012-01-01

    Background Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. Methodology/Principal Findings This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50–200 µg/mL, which were well below the concentrations required to limit bacterial growth (530–1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects. Conclusions/Significance These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections. PMID:22242149

  14. Antibiotic-specific differences in the response of Staphylococcus aureus to treatment with antimicrobials combined with manuka honey.

    PubMed

    Liu, Michael; Lu, Jing; Müller, Patrick; Turnbull, Lynne; Burke, Catherine M; Schlothauer, Ralf C; Carter, Dee A; Whitchurch, Cynthia B; Harry, Elizabeth J

    2014-01-01

    Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey synergy

  15. Prevalence of Staphylococcus aureus Colonization and Risk Factors for Infection Among Military Personnel in a Shipboard Setting.

    PubMed

    Curry, Jennifer A; Maguire, Jason D; Fraser, Jamie; Tribble, David R; Deiss, Robert G; Bryan, Coleman; Tisdale, Michele D; Crawford, Katrina; Ellis, Michael; Lalani, Tahaniyat

    2016-06-01

    Staphylococcal skin and soft tissue infections (SSTIs), especially those due to methicillin-resistant Staphylococcus aureus (MRSA) are an important public health issue for the military. Limited data exist regarding the prevalence of S. aureus colonization in the shipboard setting. We conducted a cross-sectional, observational study to determine the point prevalence of S. aureus colonization among military personnel onboard a naval vessel. Asymptomatic active duty personnel completed a survey for risk factors associated with colonization and SSTIs. Culture specimens were obtained from the anterior nares, pharynx, groin, and perirectal regions. MRSA isolates underwent testing for antimicrobial resistance, virulence factors, and pulsed-field type. 400 individuals were enrolled, 198 (49.5%) of whom were colonized with S.