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1.
Medicine (Baltimore) ; 98(38): e17185, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567961

RESUMO

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures.


Assuntos
Toxinas Bacterianas/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Pneumonia Necrosante/microbiologia , Estudos Retrospectivos , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia
2.
Acta Chir Orthop Traumatol Cech ; 86(4): 276-280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31524589

RESUMO

PURPOSE OF THE STUDY Septic arthritis is an infection of joints caused by a pathogenic microorganism. Septic arthritis has a mortality rate of 11-40% when it's not treated properly. The mortality rate with methicillin-sensitive Staphylococcus aureus (MSSA)is 5-7%, while the rate with methicillin-resistant Staphylococcus aureus (MRSA)is 13-20%. The aim of this study is to evaluate the effects of intraarticular vancomycin and teicoplanin on joint cartilage in in vivo settings and its utility in routine MRSA treatment. MATERIALS AND METHODS In our study, 35 male Sprague-Dawley rats aged 28 days were used. Rats were obtained from the Regenerative and Restorative Medicine Research Center (REMER) of Istanbul Medipol University. Rats were randomly divided into 5 groups each containing 7 rats. Joint injections were administered with isoflurane analgesia every day at 6 am. Three rats (15 rats) from each group were sacrified in seventh day and evaluated immunohistologically to evaluate acute healing in articular cartilage. All remaining rats were sacrificed on day 28 and their knees were evaluated by immunohistochemical examination. RESULTS In our study, there were no complications in any rat during injection and the study period. Hematoxylin eosin (H & E) histological staining for evaluating cartilage healing and healing levels did not show statistically significant differences between the groups at first week (p > 0.05). Matrix metalloproteinase-13 (MMP-13) staining did not show any statistically significant difference between the groups. (p > 0.05). DISCUSSION MRSAseptic arthritis, diagnosed for the first time in 1960, has recently been responsible for 6-22% of all septic arthritis and is increasing day by day. The use of systemic vancomycin or teicoplanin is the first-line treatment method in MRSA septic arthritis. Serum levels reach the desired level, especially with intravenous infusion dose. On the other hand, it has been shown that intraarticular concentration does not reach a sufficient level in studies conducted. The use of intraarticular antibiotics during treatment can lead to more effective and early disease control by turning this negative situation into favor of the patient. As a result, intraarticular vancomycin and teicoplanin maximale tolerable and maintenance doses can be safely used beside surgery and intravenous antibiotics to increase efficacy of treatment, reduction of recurrence rates and reduction of mortality in MRSAseptic arthritis. CONCLUSIONS Intraarticular vancomycin and teicoplanin maximale tolerable and maintenance doses can be safely used beside surgery and intravenous antibiotics to increase efficacy of treatment, reduction of recurrence rates and reduction of mortality in MRSA septic arthritis. Key words:arthritis, infectious; methicillin-resistant Staphylococcus aureus; mortality.


Assuntos
Antibacterianos/administração & dosagem , Artrite Infecciosa/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Teicoplanina/administração & dosagem , Vancomicina/administração & dosagem , Animais , Artrite Infecciosa/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Modelos Animais de Doenças , Membro Posterior/efeitos dos fármacos , Membro Posterior/microbiologia , Injeções Intra-Articulares , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/patologia , Cicatrização/efeitos dos fármacos
3.
PLoS Pathog ; 15(6): e1007877, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31226163

RESUMO

Rapid bone destruction often leads to permanent joint dysfunction in patients with septic arthritis, which is mainly caused by Staphylococcus aureus (S. aureus). Staphylococcal cell wall components are known to induce joint inflammation and bone destruction. Here, we show that a single intra-articular injection of S. aureus lipoproteins (Lpps) into mouse knee joints induced chronic destructive macroscopic arthritis through TLR2. Arthritis was characterized by rapid infiltration of neutrophils and monocytes. The arthritogenic effect was mediated mainly by macrophages/monocytes and partially via TNF-α but not by neutrophils. Surprisingly, a S. aureus mutant lacking Lpp diacylglyceryl transferase (lgt) caused more severe joint inflammation, which coincided with higher bacterial loads of the lgt mutant in local joints than those of its parental strain. Coinjection of pathogenic S. aureus LS-1 with staphylococcal Lpps into mouse knee joints caused improved bacterial elimination and diminished bone erosion. The protective effect of the Lpps was mediated by their lipid moiety and was fully dependent on TLR2 and neutrophils. The blocking of CXCR2 on neutrophils resulted in total abrogation of the protective effect of the Lpps. Our data demonstrate that S. aureus Lpps elicit innate immune responses, resulting in a double-edged effect. On the one hand, staphylococcal Lpps boost septic arthritis. On the other hand, Lpps act as adjuvants and activate innate immunity, which could be useful for combating infections with multiple drug-resistant strains.


Assuntos
Artrite/imunologia , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Neutrófilos/imunologia , Staphylococcus aureus/imunologia , Animais , Artrite/genética , Artrite/microbiologia , Artrite/patologia , Proteínas de Bactérias/genética , Feminino , Lipoproteínas/genética , Camundongos , Neutrófilos/patologia , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/imunologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
4.
Microbiol Immunol ; 63(3-4): 147-150, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31037765

RESUMO

It is not known how Leptospira react to wound or a cut infected with microbes, such as pathogenic Staphylococcus, or their common habitat on oral or nasal mucosal membranes. In the present study, Staphylococcus aureus MTCC-737 showed strong co-aggregation with leptospiral strains (>75%, visual score of + 4) in vitro. All tested strains of Leptospira were able to form biofilm with S. aureus. Scanning electron microscopy analysis revealed intertwined networks of attached cells of L. interrogans and S. aureus, thus providing evidence of a matrix-like structure. This phenomenon may have implications in Leptospira infection, which occurs via cuts and wounds of the skin.


Assuntos
Biofilmes/crescimento & desenvolvimento , Leptospira interrogans/crescimento & desenvolvimento , Interações Microbianas/fisiologia , Dermatopatias Bacterianas/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Coinfecção/microbiologia , Coinfecção/patologia , Leptospirose/microbiologia , Leptospirose/patologia , Microscopia Eletrônica de Varredura , Dermatopatias Bacterianas/patologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia
5.
PLoS Pathog ; 15(5): e1007803, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31112582

RESUMO

Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are known as causative agents of emetic food poisoning. We previously demonstrated that SEA binds with submucosal mast cells and evokes mast cell degranulation in a small emetic house musk shrew model. Notably, primates have been recognized as the standard model for emetic assays and analysis of SE emetic activity. However, the mechanism involved in SEA-induced vomiting in primates has not yet been elucidated. In the present study, we established common marmosets as an emetic animal model. Common marmosets were administered classical SEs, including SEA, SEB and SEC, and exhibited multiple vomiting responses. However, a non-emetic staphylococcal superantigen, toxic shock syndrome toxin-1, did not induce emesis in these monkeys. These results indicated that the common marmoset is a useful animal model for assessing the emesis-inducing activity of SEs. Furthermore, histological analysis uncovered that SEA bound with submucosal mast cells and induced mast cell degranulation. Additionally, ex vivo and in vivo pharmacological results showed that SEA-induced histamine release plays a critical role in the vomiting response in common marmosets. The present results suggested that 5-hydroxytryptamine also plays an important role in the transmission of emetic stimulation on the afferent vagus nerve or central nervous system. We conclude that SEA induces histamine release from submucosal mast cells in the gastrointestinal tract and that histamine contributes to the SEA-induced vomiting reflex via the serotonergic nerve and/or other vagus nerve.


Assuntos
Eméticos/toxicidade , Enterotoxinas/toxicidade , Liberação de Histamina/efeitos dos fármacos , Mastócitos/metabolismo , Intoxicação Alimentar Estafilocócica/etiologia , Staphylococcus/patogenicidade , Vômito/induzido quimicamente , Animais , Callithrix , Modelos Animais de Doenças , Intestinos/efeitos dos fármacos , Intestinos/patologia , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Reflexo , Intoxicação Alimentar Estafilocócica/metabolismo , Intoxicação Alimentar Estafilocócica/patologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Vômito/microbiologia
6.
PLoS Pathog ; 15(5): e1007800, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31116795

RESUMO

Staphylococcus aureus is a leading cause of endovascular infections. This bacterial pathogen uses a diverse array of surface adhesins to clump in blood and adhere to vessel walls, leading to endothelial damage, development of intravascular vegetations and secondary infectious foci, and overall disease progression. In this work, we describe a novel strategy used by S. aureus to control adhesion and clumping through activity of the ArlRS two-component regulatory system, and its downstream effector MgrA. Utilizing a combination of in vitro cellular assays, and single-cell atomic force microscopy, we demonstrated that inactivation of this ArlRS-MgrA cascade inhibits S. aureus adhesion to a vast array of relevant host molecules (fibrinogen, fibronectin, von Willebrand factor, collagen), its clumping with fibrinogen, and its attachment to human endothelial cells and vascular structures. This impact on S. aureus adhesion was apparent in low shear environments, and in physiological levels of shear stress, as well as in vivo in mouse models. These effects were likely mediated by the de-repression of giant surface proteins Ebh, SraP, and SasG, caused by inactivation of the ArlRS-MgrA cascade. In our in vitro assays, these giant proteins collectively shielded the function of other surface adhesins and impaired their binding to cognate ligands. Finally, we demonstrated that the ArlRS-MgrA regulatory cascade is a druggable target through the identification of a small-molecule inhibitor of ArlRS signaling. Our findings suggest a novel approach for the pharmacological treatment and prevention of S. aureus endovascular infections through targeting the ArlRS-MgrA regulatory system.


Assuntos
Aderência Bacteriana , Proteínas de Bactérias/metabolismo , Endotélio Vascular/microbiologia , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Animais , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Fibrinogênio/genética , Fibrinogênio/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia
7.
Emerg Microbes Infect ; 8(1): 707-716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119985

RESUMO

Staphylococcus aureus (S. aureus) is one of the most serious human pathogens. α-Hemolysin (Hla) secreted by S. aureus is a key toxin for various infections. We herein report that Honokiol, a natural plant polyphenol, inhibits the secretion and hemolytic activity of staphylococcal Hla with concomitant growth inhibition of S. aureus and protection of S. aureus-mediated cell injury within subinhibitory concentrations. In parallel, Honokiol attenuates the staphylococcal Hla-induced inflammatory response by inhibiting NLRP3 inflammasome activation in vitro and in vivo. Consequently, the biologically active forms of the inflammatory cytokines IL-1ß and IL-18 are reduced significantly in response to Honokiol in mice infected with S. aureus. Experimentally, we confirm that Honokiol binds to monomeric Hla with a modest affinity without impairing its oligomerization. Based on molecular docking analyses in silico, we make a theoretical discovery that Honokiol is located outside of the triangular region of monomeric Hla. The binding model restricts the function of the residues related to membrane channel formation, which leads to the functional disruption of the assembled membrane channel. This research creates a new paradigm for developing therapeutic agents against staphylococcal Hla-mediated infections.


Assuntos
Toxinas Bacterianas/metabolismo , Compostos de Bifenilo/administração & dosagem , Proteínas Hemolisinas/metabolismo , Inflamassomos/antagonistas & inibidores , Lignanas/administração & dosagem , Receptores de Superfície Celular/antagonistas & inibidores , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Células A549 , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Toxinas Bacterianas/toxicidade , Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas Hemolisinas/toxicidade , Histocitoquímica , Humanos , Lignanas/metabolismo , Lignanas/farmacologia , Fígado/patologia , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Ligação Proteica , Infecções Estafilocócicas/patologia , Staphylococcus aureus/metabolismo , Resultado do Tratamento
8.
PLoS Negl Trop Dis ; 13(5): e0007247, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31107882

RESUMO

Cutaneous leishmaniasis (CL) is a parasitic disease causing chronic, ulcerating skin lesions. Most humans infected with the causative Leishmania protozoa are asymptomatic. Leishmania spp. are usually introduced by sand flies into the dermis of mammalian hosts in the presence of bacteria from either the host skin, sand fly gut or both. We hypothesized that bacteria at the dermal inoculation site of Leishmania major will influence the severity of infection that ensues. A C57BL/6 mouse ear model of single or coinfection with Leishmania major, Staphylococcus aureus, or both showed that single pathogen infections caused localized lesions that peaked after 2-3 days for S. aureus and 3 weeks for L. major infection, but that coinfection produced lesions that were two-fold larger than single infection throughout 4 weeks after coinfection. Coinfection increased S. aureus burdens over 7 days, whereas L. major burdens (3, 7, 28 days) were the same in singly and coinfected ears. Inflammatory lesions throughout the first 4 weeks of coinfection had more neutrophils than did singly infected lesions, and the recruited neutrophils from early (day 1) lesions had similar phagocytic and NADPH oxidase capacities. However, most neutrophils were apoptotic, and transcription of immunomodulatory genes that promote efferocytosis was not upregulated, suggesting that the increased numbers of neutrophils may, in part, reflect defective clearance and resolution of the inflammatory response. In addition, the presence of more IL-17A-producing γδ and non-γδ T cells in early lesions (1-7 days), and L. major antigen-responsive Th17 cells after 28 days of coinfection, with a corresponding increase in IL-1ß, may recruit more naïve neutrophils into the inflammatory site. Neutralization studies suggest that IL-17A contributed to an enhanced inflammatory response, whereas IL-1ß has an important role in controlling bacterial replication. Taken together, these data suggest that coinfection of L. major infection with S. aureus exacerbates disease, both by promoting more inflammation and neutrophil recruitment and by increasing neutrophil apoptosis and delaying resolution of the inflammatory response. These data illustrate the profound impact that coinfecting microorganisms can exert on inflammatory lesion pathology and host adaptive immune responses.


Assuntos
Coinfecção/imunologia , Interleucina-17/imunologia , Leishmania major/fisiologia , Leishmaniose Cutânea/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/fisiologia , Animais , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/patologia , Feminino , Humanos , Interleucina-17/genética , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Leishmania major/genética , Leishmania major/isolamento & purificação , Leishmaniose Cutânea/genética , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Células Th17/imunologia
9.
Prev Vet Med ; 167: 16-23, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31027715

RESUMO

The purpose of this study was to improve the diagnostic recommendations for Staphylococcus aureus and Streptococcus agalactiae control using bacterial culture (BC), polymerase chain reaction (PCR) and somatic cell count (SCC) as diagnostic methods. The study was carried out in three steps: firstly, diagnostic test patterns for naturally infected quarters with Staph. aureus (24 quarters) and Strep. agalactiae (16 quarters) were created by sampling the quarters each day for 21 days and analysing the daily quarter milk samples using BC, PCR and SCC. Secondly, 30 mastitis experts were asked to group and describe the diagnostic test patterns and to establish a diagnosis for each group. The experts' statements regarding the groups they established were subsequently examined using qualitative content analysis to assign "infection types" to the statements. Lastly, the test performance was estimated for BC, PCR and SCC using generalised logistic regression models with the interpreted statements as a reference for infection. The experts mainly identified the Staph. aureus quarter-patterns as persistent infections, while some had more dynamic patterns. Strep. agalactiae quarter-patterns mainly involved persistent infection, yet some appeared hard to diagnose and were assigned to almost all different infection types, while experts did not agree on the interpretation. Estimates of Se for detection of Staph. aureus infection were 95.9% [93.7; 97.3] for BC, 99.5% [98.3; 99.8] for PCR, and 96.1% [94.0; 97.5] for SCC. The corresponding Sp estimates were 74.5% [65.7; 81.7], 66% [57.2; 73.8] and 43.7% [36.2; 51.5] for BC, PCR and SCC, respectively. The Se estimates of BC and PCR for Strep. agalactiae infection were 100% [83.5; 100] and 99.9% [99.6; 100], respectively, whereas the Se of SCC detecting Strep. agalactiae infection was only 34.3% [26.4; 43.3]. This indicated that Strep. agalactiae-positive BC and PCR test results were more important than SCC results to the experts when diagnosing a quarter as infected. The Sp estimates of BC, PCR and SCC for Strep. agalactiae infection were 99% [72.8; 100], 97.7% [62.1; 99.9], and 65.7% [56.7; 73.7], respectively. We conclude that PCR and BC are highly sensitive in the detection of persistent and new infections as defined by the experts, although the Se was not always 100%. An accepted lower Sp suggests that experts place less emphasis on false-positive results. We recommend that efforts are made to develop consistent terminology to characterise intramammary infections over time so that the course of infection can be taken into account at diagnosis.


Assuntos
Mastite Bovina/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae , Animais , Bovinos , Testes Diagnósticos de Rotina/veterinária , Feminino , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/diagnóstico , Mastite Bovina/patologia , Sensibilidade e Especificidade , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia
10.
Eur Cell Mater ; 37: 265-276, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30957870

RESUMO

Periprosthetic infection in total knee arthroplasty is a difficult-to-treat complication. Current implant revision procedures use non-degradable, antibiotic-loaded bone cement for local antimicrobial delivery. As a permanent foreign body, antibiotic-loaded bone cement is susceptible to bacterial colonisation after antibiotic release. In this first step, of a multi-study approach, an infection prevention model assessed a resorbable, antibiotic-eluting bone-void filler for preventing infection in a large animal model. Four groups of sheep were utilised to monitor antibiotic-eluting bone-void filler-induced osteoconductivity, infection prevention, and implant resorption. Explanted bone and surrounding tissues were evaluated using quantitative microbiology, backscattered electron microscopy, bone mineral apposition, and Sanderson's staining at the 12-week endpoint. Control groups received commercially available bone-void filler, implanted into a surgically created defect on the right medial femoral condyle. Experimental groups received six antibiotic-eluting bone-void filler devices placed into identically sized defects. One control and one experimental group tested osteoconductivity. An additional control and experimental group were each inoculated with 5 × 105 colony forming units/mL Staphylococcus aureus during implant placement for bactericidal effects. Osteoconductivity was confirmed for both antibiotic-eluting bone-void filler and commercially available bone-void filler. The experimental group inoculated with S. aureus showed no detectable bacteria at the study's 12-week endpoint, while infection controls required euthanasia 6-11 d post-inoculation due to infection. This large animal study validated this antibiotic-eluting bone-void filler as osteoconductive, in situ degradable, and bactericidal. All groups, except the infection control, exhibited bone formation comparable to commercial filler ProOsteon®500R.


Assuntos
Antibacterianos , Cimentos para Ossos , Regeneração Óssea/efeitos dos fármacos , Fêmur/metabolismo , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/metabolismo , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Cimentos para Ossos/química , Cimentos para Ossos/farmacocinética , Cimentos para Ossos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Fêmur/microbiologia , Fêmur/patologia , Ovinos , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia
11.
Nat Commun ; 10(1): 1149, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30850614

RESUMO

Treatment failure in biofilm-associated bacterial infections is an important healthcare issue. In vitro studies and mouse models suggest that bacteria enter a slow-growing/non-growing state that results in transient tolerance to antibiotics in the absence of a specific resistance mechanism. However, little clinical confirmation of antibiotic tolerant bacteria in patients exists. In this study we investigate a Staphylococcus epidermidis pacemaker-associated endocarditis, in a patient who developed a break-through bacteremia despite taking antibiotics to which the S. epidermidis isolate is fully susceptible in vitro. Characterization of the clinical S. epidermidis isolates reveals in-host evolution over the 16-week infection period, resulting in increased antibiotic tolerance of the entire population due to a prolonged lag time until growth resumption and a reduced growth rate. Furthermore, we observe adaptation towards an increased biofilm formation capacity and genetic diversification of the S. epidermidis isolates within the patient.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Resistência a Múltiplos Medicamentos/genética , Endocardite/microbiologia , Interações Hospedeiro-Patógeno/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/genética , Adulto , Bacteriemia/tratamento farmacológico , Bacteriemia/patologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Tolerância a Medicamentos/genética , Endocardite/tratamento farmacológico , Endocardite/patologia , Evolução Molecular , Fluoroquinolonas/farmacologia , Glicopeptídeos/farmacologia , Humanos , Mutação INDEL , Masculino , Testes de Sensibilidade Microbiana , Marca-Passo Artificial/microbiologia , Peptídeos Cíclicos/farmacologia , Filogenia , Polimorfismo de Nucleotídeo Único , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/crescimento & desenvolvimento , Staphylococcus epidermidis/isolamento & purificação , beta-Lactamas/farmacologia
12.
Infect Immun ; 87(5)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30833335

RESUMO

Numerous factors have, to date, been identified as playing a role in the regulation of Agr activity in Staphylococcus aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigated the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mroQ mutant, we observed a drastic reduction in proteolysis, hemolysis, and pigmentation that was fully complementable. This appears to result from diminished agr activity, as transcriptional analysis revealed significant decreases in expression of both RNAII and RNAIII in the mroQ mutant. Such effects appear to be direct, rather than indirect, as known agr effectors demonstrated limited alterations in their activity upon mroQ disruption. A comparison of RNA sequencing data sets for both mroQ and agr mutants revealed a profound overlap in their regulomes, with the majority of factors affected being known virulence determinants. Importantly, the preponderance of alterations in expression were more striking in the agr mutant, indicating that MroQ is necessary, but not sufficient, for Agr function. Mechanism profiling revealed that putative residues for metalloprotease activity within MroQ are required for its Agr-controlling effect; however, this was not wielded at the level of AgrD processing. Virulence assessment demonstrated that both mroQ and agr mutants exhibited increased formation of renal abscesses but decreased skin abscess formation alongside diminished dermonecrosis. Collectively, we present the characterization of a novel agr effector in S. aureus which would appear to be a direct regulator, potentially functioning via interaction with the AgrC histidine kinase.


Assuntos
Proteínas de Bactérias/imunologia , Regulação Bacteriana da Expressão Gênica/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/imunologia , Fatores de Transcrição/imunologia , Fatores de Virulência/imunologia , Animais , Proteínas de Bactérias/genética , Feminino , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Camundongos , Modelos Animais , Infecções Estafilocócicas/genética , Staphylococcus aureus/genética , Fatores de Transcrição/genética , Fatores de Virulência/genética
13.
ACS Appl Mater Interfaces ; 11(13): 12298-12307, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30855125

RESUMO

Craniotomy involves the removal of a skull fragment to access the brain, such as during tumor or epilepsy surgery, which is immediately replaced intraoperatively. The infection incidence after craniotomy ranges from 0.8 to 3%, with approximately half caused by Staphylococcus aureus ( S. aureus). To mitigate infectious complications following craniotomy, we engineered a three-dimensional (3D) bioprinted bone scaffold to harness the potent antibacterial activity of macrophages (MΦs) together with antibiotics using a mouse S. aureus craniotomy-associated biofilm model that establishes a persistent infection on the bone flap, subcutaneous galea, and brain. The 3D scaffold contained rifampin and daptomycin printed in a composite slurry, with viable MΦs incorporated into a hydrogel-based bioink, which was assessed for both the treatment and prevention of craniotomy-associated infections in the mouse model. For the treatment paradigm, the bone flap was removed at day 7 post infection after a mature biofilm had formed and was replaced with a 3D printed antibiotic scaffold, with or without MΦ incorporation. Bacterial burdens in the galea and brain were reduced by at least 100-fold at early time points, which was potentiated by bioprinting viable MΦs into the 3D antibiotic scaffold. We also examined a prevention paradigm, where the scaffolds were placed at the time of surgery and challenged with S. aureus one day later at the surgical site. Interestingly, unlike the treatment paradigm, the incorporation of viable MΦs into the 3D antibiotic scaffold did not enhance bacterial clearance compared to that of antibiotic alone. With further refinement, our 3D bioprinted scaffold represents a potential treatment modality, as it delivers therapeutic antibiotic levels more rapidly than systemic administration, based on its proximity to the infection site. In addition, the incorporation of viable MΦs into the 3D scaffold is an important advance, which demonstrated an improved therapeutic benefit for the treatment of established biofilms that represent the most clinically challenging scenario.


Assuntos
Antibacterianos , Craniotomia , Macrófagos , Impressão Tridimensional , Infecções Estafilocócicas , Staphylococcus aureus/fisiologia , Infecção dos Ferimentos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Feminino , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia , Infecção dos Ferimentos/metabolismo , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/terapia
14.
PLoS One ; 14(3): e0213590, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870491

RESUMO

Cerament (Bonesupport Holding, Lund, Sweden) is a bioresorbable synthetic bone substitute consisting of calcium sulfate and hydroxyapatite which is successfully used as a bone graft in bone defects or in delayed and non-unions after fractures. Besides, calcium sulfate/ hydroxyapatite (CAS/HA) could have, attributed to its composition and osteoinductive properties, have great importance in the treatment of bone infections with critical size defects (CSD). Aim of the study was to evaluate the effects of antibiotic infused CAS/HA on inflammation and bone healing in an implant-associated osteitis mice model. In a standardized murine model, the left femur of 72 BALB/c mice were osteotomized, generating a CSD (2,5 mm) with stabilization through a 6-hole titanium locking plate. Osteitis has been induced through inoculation of Staphylococcus aureus (SA) into the fracture gap. To analyze the effect of CAS/HA, following groups were generated with either CAS/HA, CAS/HA with gentamycin (CAS/ HA-G) or CAS/HA with vancomycin (CAS/HA-V) insets placed into the osteotomy. Debridément and lavages were progressed on day 7 and 42 to determine the local bacterial growth and the immune reaction. Fracture healing was quantified on day 7 and 42 by x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of Interleukin (IL)- 6 and polymorphonuclear neutrophils (PMN) in lavage samples. Osteitis induced higher IL-6 and PMN-levels in the lavage samples on day 7. Both parameters showed a reduction in all groups on day 42. CAS/HA-V revealed a significant reduction of CFU and PMNs in lavage samples on day 42. A positive effect on bone healing could only be shown in non-infected mice. Whereas, application of mere CAS/HA in infected mice did show tendencies of bone destruction and lysis, independent of impregnation with antibiotics or not. Thus, application of CAS/HA in acute implant-associated infections is not recommended. In non-infectious environments or after infect-convalescence CAS/HA could albeit serve as a suggestive tool in trauma and orthopedic surgery.


Assuntos
Antibacterianos/farmacologia , Placas Ósseas , Sulfato de Cálcio/farmacologia , Durapatita/farmacologia , Fraturas do Fêmur/terapia , Osteíte/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Animais , Antibacterianos/química , Sulfato de Cálcio/química , Modelos Animais de Doenças , Durapatita/química , Feminino , Fraturas do Fêmur/metabolismo , Fraturas do Fêmur/microbiologia , Fraturas do Fêmur/patologia , Consolidação da Fratura/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Osteíte/etiologia , Osteíte/metabolismo , Osteíte/patologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia
15.
Neurol Res ; 41(5): 399-412, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30707086

RESUMO

OBJECTIVE: Ischaemic brain lesions and brain abscesses are frequent in both human and animal cases of septic embolic stroke. However, existing models of brain infection do not reflect central aspects of septic embolic stroke. Our aim was to compare septic and non-septic embolic stroke in order to identify gene expressions, inflammatory mediators and brain damage in a rat model. METHODS: We created precisely located focal brain infarcts in a rat model of Staphylococcus aureus infected embolic stroke. To cause septic embolic stroke we used a fibrin-rich embolus with bacteria, while every rat in the control group received a non-infected embolus. 64 rats were randomized to receive sham-surgery, sterile embolic stroke or septic embolic stroke. All groups were compared for brain pathology, mortality, gene expressions and inflammatory mediators using histology and reverse transcription quantitative real-time PCR. RESULTS: Although infarct volumes did not differ, septic embolic stroke caused higher mortality than sterile embolic stroke (p=  0.002). Brain abscesses were observed only in the septic group. Approximately 400-500 fold increases were observed for Orm1 and Cxcl2 respectively (1.00E-08 < p < 1.92E-07) in the septic group compared to the sterile group, and these were the most dramatically regulated genes in septic embolic stroke compared to sterile embolic stroke. CONCLUSIONS: Septic embolic stroke caused brain abscesses, increased mortality and upregulated Orm1 and Cxcl2 gene expressions compared to non-infected embolic stroke. The dramatic Orm1 increase observed in the septic group is unprecedented and suggests a significant biological role of Orm1 during septic neuroinflammation.


Assuntos
Quimiocina CXCL2/metabolismo , Embolia Intracraniana/metabolismo , Orosomucoide/metabolismo , Sepse/metabolismo , Infecções Estafilocócicas/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Abscesso Encefálico/metabolismo , Abscesso Encefálico/patologia , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Embolia Intracraniana/patologia , Masculino , Distribuição Aleatória , Ratos Sprague-Dawley , Sepse/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus , Acidente Vascular Cerebral/patologia , Regulação para Cima
16.
Cell Prolif ; 52(2): e12565, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30729611

RESUMO

OBJECTIVES: The lung-gut axis is known to be involved in the pathogenesis of Staphylococcus aureus pneumonia. However, the underlying mechanisms remain unclear. We examined the role of pulmonary mast cells (MCs) in the regulation of the lung-gut axis during S. aureus pneumonia. MATERIALS AND METHODS: We created a mouse model of S. aureus pneumonia using MC-deficient mice (KitW-sh/W-sh ) and examined the level of inflammation, bacterial burden, expression of cathelicidin-related antimicrobial peptide (CRAMP) and composition of the gut microbiota. We further evaluated anti-bacterial immunity by administering bone marrow MCs (BMMCs) or CRAMP into the lungs of KitW-sh/W-sh mice. RESULTS: After S. aureus challenge, the MC-deficient mice, compared with wild-type (WT) mice, displayed attenuated lung inflammation, decreased expression of CRAMP, higher bacterial lung load and disturbance of the intestinal microbiota. Adoptive transfer of BMMCs into the lung effectively reconstituted the host defence against S. aureus in KitW-sh/W-sh mice, thus resulting in recovery of S. aureus pneumonia-induced intestinal dysfunction. Similarly, exogenous administration of CRAMP significantly enhanced anti-bacterial immunity in the lungs of MC-deficient mice. CONCLUSIONS: This study provides evidence for the involvement of MCs in the regulation of the lung-gut axis during S. aureus pneumonia.


Assuntos
Microbioma Gastrointestinal , Inflamação/imunologia , Pulmão/imunologia , Mastócitos/imunologia , Pneumonia/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Modelos Animais de Doenças , Inflamação/microbiologia , Inflamação/patologia , Pulmão/microbiologia , Pulmão/patologia , Mastócitos/microbiologia , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/microbiologia , Pneumonia/patologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia
17.
Microbiol Spectr ; 7(1)2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30737913

RESUMO

Sortases cleave short peptide motif sequences at the C-terminal end of secreted surface protein precursors and either attach these polypeptides to the peptidoglycan of Gram-positive bacteria or promote their assembly into pilus structures that are also attached to peptidoglycan. Sortase A, the enzyme first identified in the human pathogen Staphylococcus aureus, binds LPXTG motif sorting signals, cleaves between threonine (T) and glycine (G) residues, and forms an acyl enzyme between its active-site cysteine thiol and the carboxyl group of threonine (T). Sortase A acyl enzyme is relieved by the nucleophilic attack of the cross bridge amino group within lipid II, thereby generating surface protein linked to peptidoglycan precursor. Such products are subsequently incorporated into the cell wall envelope by enzymes of the peptidoglycan synthesis pathway. Surface proteins linked to peptidoglycan may be released from the bacterial envelope to diffuse into host tissues and fulfill specific biological functions. S. aureus sortase A is essential for host colonization and for the pathogenesis of invasive diseases. Staphylococcal sortase-anchored surface proteins fulfill key functions during the infectious process, and vaccine-induced antibodies targeting surface proteins may provide protection against S. aureus. Alternatively, small-molecule inhibitors of sortase may be useful agents for the prevention of S. aureus colonization and invasive disease.


Assuntos
Aminoaciltransferases/imunologia , Aminoaciltransferases/metabolismo , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/imunologia , Cisteína Endopeptidases/metabolismo , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Peptidoglicano/metabolismo , Vacinas Antiestafilocócicas/imunologia , Staphylococcus aureus/patogenicidade , Anticorpos Antibacterianos/imunologia , Humanos , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/imunologia
18.
Infect Immun ; 87(5)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804099

RESUMO

Influenza kills 30,000 to 40,000 people each year in the United States and causes 10 times as many hospitalizations. A common complication of influenza is bacterial superinfection, which exacerbates morbidity and mortality from the viral illness. Recently, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as the dominant pathogen found in bacterial superinfection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial superinfection. Current therapy for influenza/bacterial superinfection consists of treating the underlying influenza infection and adding various antibiotics, which are increasingly rendered ineffective by rising bacterial multidrug resistance. Several groups have recently proposed the use of the antiviral cytokine interferon lambda (IFN-λ) as a therapeutic for influenza, as administration of pegylated IFN-λ improves lung function and survival during influenza by reducing the overabundance of neutrophils in the lung. However, our data suggest that therapeutic IFN-λ impairs bacterial clearance during influenza superinfection. Specifically, mice treated with an adenoviral vector to overexpress IFN-λ during influenza infection exhibited increased bacterial burdens upon superinfection with either MRSA or S. pneumoniae Surprisingly, adhesion molecule expression, antimicrobial peptide production, and reactive oxygen species activity were not altered by IFN-λ treatment. However, neutrophil uptake of MRSA and S. pneumoniae was significantly reduced upon IFN-λ treatment during influenza superinfection in vivo Together, these data support the theory that IFN-λ decreases neutrophil motility and function in the influenza-infected lung, which increases the bacterial burden during superinfection. Thus, we believe that caution should be exercised in the possible future use of IFN-λ as therapy for influenza.


Assuntos
Antivirais/uso terapêutico , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Interferons/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Superinfecção/tratamento farmacológico , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/patologia , Superinfecção/etiologia , Estados Unidos
19.
MBio ; 10(1)2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808698

RESUMO

Manganese (Mn) is an essential micronutrient critical for the pathogenesis of Staphylococcus aureus, a significant cause of human morbidity and mortality. Paradoxically, excess Mn is toxic; therefore, maintenance of intracellular Mn homeostasis is required for survival. Here we describe a Mn exporter in S. aureus, MntE, which is a member of the cation diffusion facilitator (CDF) protein family and conserved among Gram-positive pathogens. Upregulation of mntE transcription in response to excess Mn is dependent on the presence of MntR, a transcriptional repressor of the mntABC Mn uptake system. Inactivation of mntE or mntR leads to reduced growth in media supplemented with Mn, demonstrating MntE is required for detoxification of excess Mn. Inactivation of mntE results in elevated levels of intracellular Mn, but reduced intracellular iron (Fe) levels, supporting the hypothesis that MntE functions as a Mn efflux pump and Mn efflux influences Fe homeostasis. Strains inactivated for mntE are more sensitive to the oxidants NaOCl and paraquat, indicating Mn homeostasis is critical for resisting oxidative stress. Furthermore, mntE and mntR are required for full virulence of S. aureus during infection, suggesting S. aureus experiences Mn toxicity in vivo Combined, these data support a model in which MntR controls Mn homeostasis by balancing transcriptional repression of mntABC and induction of mntE, both of which are critical for S. aureus pathogenesis. Thus, Mn efflux contributes to bacterial survival and virulence during infection, establishing MntE as a potential antimicrobial target and expanding our understanding of Mn homeostasis.IMPORTANCE Manganese (Mn) is generally viewed as a critical nutrient that is beneficial to pathogenic bacteria due to its function as an enzymatic cofactor and its capability of acting as an antioxidant; yet paradoxically, high concentrations of this transition metal can be toxic. In this work, we demonstrate Staphylococcus aureus utilizes the cation diffusion facilitator (CDF) family protein MntE to alleviate Mn toxicity through efflux of excess Mn. Inactivation of mntE leads to a significant reduction in S. aureus resistance to oxidative stress and S. aureus -mediated mortality within a mouse model of systemic infection. These results highlight the importance of MntE-mediated Mn detoxification in intracellular Mn homeostasis, resistance to oxidative stress, and S. aureus virulence. Therefore, this establishes MntE as a potential target for development of anti-S. aureus therapeutics.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Manganês/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Animais , Proteínas de Transporte de Cátions/genética , Modelos Animais de Doenças , Regulação Bacteriana da Expressão Gênica , Homeostase , Ferro/metabolismo , Manganês/toxicidade , Camundongos Endogâmicos BALB C , Viabilidade Microbiana , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Genética , Virulência/efeitos dos fármacos
20.
MBio ; 10(1)2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723124

RESUMO

Small RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria in general and in Gram-positive bacteria in particular. In the major human pathogen Staphylococcus aureus, hundreds of sRNAs have been identified; however, only a few have been characterized in detail. In this study, we investigate the role of the sRNA Teg41 in S. aureus virulence. We demonstrate that Teg41, an sRNA divergently transcribed from the locus that encodes the cytolytic alpha phenol-soluble modulin (αPSM) peptides, plays a critical role in αPSM production. Overproduction of Teg41 leads to an increase in αPSM levels and a corresponding increase in hemolytic activity from S. aureus cells and cell-free culture supernatants. To identify regions of Teg41 important for its function, we performed an in silico RNA-RNA interaction analysis which predicted an interaction between the 3' end of Teg41 and the αPSM transcript. Deleting a 24-nucleotide region from the S. aureus genome, corresponding to the 3' end of Teg41, led to a 10-fold reduction in αPSM-dependent hemolytic activity and attenuation of virulence in a murine abscess model of infection. Restoration of hemolytic activity in the Teg41Δ3' strain was possible by expressing full-length Teg41 in trans Restoration of hemolytic activity was also possible by expressing the 3' end of Teg41, suggesting that this region of Teg41 is necessary and sufficient for αPSM-dependent hemolysis. Our results show that Teg41 is positively influencing αPSM production, demonstrating for the first time regulation of the αPSM peptides by an sRNA in S. aureus IMPORTANCE The alpha phenol-soluble modulins (αPSMs) are among the most potent toxins produced by Staphylococcus aureus Their biological role during infection has been studied in detail; however, the way they are produced by the bacterial cell is not well understood. In this work, we identify a small RNA molecule called Teg41 that plays an important role in αPSM production by S. aureus Teg41 positively influences αPSM production. The importance of Teg41 is highlighted by the fact that a strain containing a deletion in the 3' end of Teg41 produces significantly less αPSMs and is attenuated for virulence in a mouse abscess model of infection. As the search for new therapeutic strategies to combat S. aureus infection proceeds, Teg41 may represent a novel target.


Assuntos
Toxinas Bacterianas/biossíntese , Regulação Bacteriana da Expressão Gênica , RNA Bacteriano/metabolismo , Pequeno RNA não Traduzido/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/genética , Fatores de Virulência/biossíntese , Abscesso/microbiologia , Abscesso/patologia , Animais , Modelos Animais de Doenças , Teste de Complementação Genética , Hemólise , Humanos , Camundongos , Deleção de Sequência , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Virulência
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