The Experts below are selected from a list of 1374 Experts worldwide ranked by ideXlab platform
David E. Heinrichs - One of the best experts on this subject based on the ideXlab platform.
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Requirement of Staphylococcus aureus ATP-Binding Cassette-ATPase FhuC for Iron-Restricted Growth and Evidence that It Functions with More than One Iron Transporter
Journal of bacteriology, 2006Co-Authors: Craig D. Speziali, James A. Henderson, Suzanne E. Dale, Enrique D. Vinés, David E. HeinrichsAbstract:In Staphylococcus aureus, fhuCBG encodes an ATP-binding cassette (ABC) transporter that is required for the transport of iron(III)-hydroxamates; mutation of either fhuB or fhuG eliminates transport. In this paper, we describe construction and characterization of an S. aureus fhuCBG deletion strain. The delta fhuCBG::ermC mutation not only resulted in a strain that was incapable of growth on iron(III)-hydroxamates as a sole source of iron but also resulted in a strain which had a profound growth defect in iron-restricted laboratory media. The growth defect was not a result of the inability to transport iron(III)-hydroxamates since S. aureus fhuG::Tn917 and S. aureus fhuD1::Km fhuD2::Tet mutants, which are also unable to transport iron(III)-hydroxamates, do not have similar iron-restricted growth defects. Complementation experiments demonstrated that the growth defect of the delta fhuCBG::ermC mutant was the result of the inability to express FhuC and that this was the result of an inability to transport iron complexed to the S. aureus siderophore staphylobactin. Transport of iron(III)-staphylobactin is dependent upon SirA (binding protein), SirB (permease), and SirC (permease). S. aureus expressing FhuC with a Walker A K42N mutation could not utilize iron(III)-hydroxamates or iron(III)-staphylobactin as a sole source of iron, supporting the conclusion that FhuC, as expected, functions with FhuB, FhuG, and FhuD1 or FhuD2 to transport iron(III)-hydroxamates and is the "genetically unlinked" ABC-ATPase that functions with SirA, SirB, and SirC to transport iron(III)-staphylobactin. Finally, we demonstrated that the delta fhuCBG::ermC strain had decreased virulence in a murine Kidney Abscess model.
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The yjeQ gene is required for virulence of Staphylococcus aureus.
Infection and immunity, 2006Co-Authors: Tracey L. Campbell, James A. Henderson, David E. Heinrichs, Eric D. BrownAbstract:Gene products required for in vivo growth and survival of Staphylococcus aureus and other pathogens represent new targets for antimicrobial chemotherapy. In this study we created a Staphylococcus aureus yjeQ deletion strain and tested its virulence using a mouse Kidney Abscess infection model. The yjeQ deletion strain was compromised for growth in vitro and severely attenuated for virulence. We concluded that yjeQ is an attractive and novel new drug target.
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Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore.
Infection and immunity, 2004Co-Authors: Suzanne E. Dale, Amanda Doherty-kirby, Gilles A. Lajoie, David E. HeinrichsAbstract:Molecular determinants underlying the production of siderophores in the human and animal pathogen Staphylococcus aureus and the contribution of siderophore production to the virulence of this bacterium have, until now, remained undefined. Here, we show that S. aureus strains RN6390 and Newman produce siderophore when the cells are starved for iron. We further identified and characterized a nine-gene, iron-regulated operon, designated sbn and situated between sirABC and galE on the S. aureus chromosome, that is involved in the production of a siderophore. Mutation of the sbnE gene, in both RN6390 and Newman, eliminates the ability of these strains to produce a siderophore under iron-limited growth conditions, while introduction of multicopy sbnE into sbnE mutants complemented the inability of the mutants to produce the siderophore. sbnE mutants, in both the RN6390 and Newman backgrounds, displayed a drastic growth deficiency, compared to the wild type, in iron-restricted growth medium, whereas no such deficiency was observed during growth in iron-replete medium. Complemented mutants showed a restored ability to grow under iron restriction. We further showed that an sbnE mutant was compromised in a murine Kidney Abscess model of S. aureus infection, illustrating the importance of siderophore production to the pathogenicity of S. aureus. sbn genes were present in all S. aureus strains tested (and all S. aureus genome sequences) but were undetectable in any of the 13 coagulase-negative staphylococci tested, including Staphylococcus epidermidis.
Nancy E Freitag - One of the best experts on this subject based on the ideXlab platform.
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Propofol Sedation Exacerbates Kidney Pathology and Dissemination of Bacteria during Staphylococcus aureus Bloodstream Infections.
Infection and immunity, 2017Co-Authors: Lavanya Visvabharathy, Nancy E FreitagAbstract:Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for large numbers of postsurgical nosocomial infections across the United States and worldwide. Propofol anesthesia is widely used in surgery and in intensive care units, and recent evidence indicates that even brief exposure to propofol can substantially increase host susceptibility to microbial infection. Here, we delineate the impact of propofol sedation on MRSA bloodstream infections in mice in the presence and absence of prophylactic antibiotic treatment. Consistent with previous reports, brief periods of anesthesia with propofol were sufficient to significantly increase bacterial burdens and Kidney pathology in mice infected with MRSA. Propofol exposure increased neutrophilic infiltrates into the Kidney and enhanced bacterial dissemination throughout Kidney tissue. Propofol sedation reduced populations of effector phagocytes and mature dendritic cells within the Kidney and led to the apparent expansion of myeloid-derived suppressor cell-like populations. When propofol was coadministered with vancomycin prophylaxis, it dramatically increased Kidney Abscess formation and bacterial dissemination throughout Kidney tissue at early times post-S. aureus infection compared to antibiotic-treated but nonsedated animals. Taken together, our data indicate that short-term sedation with propofol significantly increases the severity of bloodstream MRSA infection, even when administered in conjunction with vancomycin prophylaxis.
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propofol increases host susceptibility to microbial infection by reducing subpopulations of mature immune effector cells at sites of infection
PLOS ONE, 2015Co-Authors: Lavanya Visvabharathy, Bobbi Xayarath, Guy L Weinberg, Rebecca A Shilling, Nancy E FreitagAbstract:Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse Kidney Abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation.
Suzanne E. Dale - One of the best experts on this subject based on the ideXlab platform.
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Requirement of Staphylococcus aureus ATP-Binding Cassette-ATPase FhuC for Iron-Restricted Growth and Evidence that It Functions with More than One Iron Transporter
Journal of bacteriology, 2006Co-Authors: Craig D. Speziali, James A. Henderson, Suzanne E. Dale, Enrique D. Vinés, David E. HeinrichsAbstract:In Staphylococcus aureus, fhuCBG encodes an ATP-binding cassette (ABC) transporter that is required for the transport of iron(III)-hydroxamates; mutation of either fhuB or fhuG eliminates transport. In this paper, we describe construction and characterization of an S. aureus fhuCBG deletion strain. The delta fhuCBG::ermC mutation not only resulted in a strain that was incapable of growth on iron(III)-hydroxamates as a sole source of iron but also resulted in a strain which had a profound growth defect in iron-restricted laboratory media. The growth defect was not a result of the inability to transport iron(III)-hydroxamates since S. aureus fhuG::Tn917 and S. aureus fhuD1::Km fhuD2::Tet mutants, which are also unable to transport iron(III)-hydroxamates, do not have similar iron-restricted growth defects. Complementation experiments demonstrated that the growth defect of the delta fhuCBG::ermC mutant was the result of the inability to express FhuC and that this was the result of an inability to transport iron complexed to the S. aureus siderophore staphylobactin. Transport of iron(III)-staphylobactin is dependent upon SirA (binding protein), SirB (permease), and SirC (permease). S. aureus expressing FhuC with a Walker A K42N mutation could not utilize iron(III)-hydroxamates or iron(III)-staphylobactin as a sole source of iron, supporting the conclusion that FhuC, as expected, functions with FhuB, FhuG, and FhuD1 or FhuD2 to transport iron(III)-hydroxamates and is the "genetically unlinked" ABC-ATPase that functions with SirA, SirB, and SirC to transport iron(III)-staphylobactin. Finally, we demonstrated that the delta fhuCBG::ermC strain had decreased virulence in a murine Kidney Abscess model.
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Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore.
Infection and immunity, 2004Co-Authors: Suzanne E. Dale, Amanda Doherty-kirby, Gilles A. Lajoie, David E. HeinrichsAbstract:Molecular determinants underlying the production of siderophores in the human and animal pathogen Staphylococcus aureus and the contribution of siderophore production to the virulence of this bacterium have, until now, remained undefined. Here, we show that S. aureus strains RN6390 and Newman produce siderophore when the cells are starved for iron. We further identified and characterized a nine-gene, iron-regulated operon, designated sbn and situated between sirABC and galE on the S. aureus chromosome, that is involved in the production of a siderophore. Mutation of the sbnE gene, in both RN6390 and Newman, eliminates the ability of these strains to produce a siderophore under iron-limited growth conditions, while introduction of multicopy sbnE into sbnE mutants complemented the inability of the mutants to produce the siderophore. sbnE mutants, in both the RN6390 and Newman backgrounds, displayed a drastic growth deficiency, compared to the wild type, in iron-restricted growth medium, whereas no such deficiency was observed during growth in iron-replete medium. Complemented mutants showed a restored ability to grow under iron restriction. We further showed that an sbnE mutant was compromised in a murine Kidney Abscess model of S. aureus infection, illustrating the importance of siderophore production to the pathogenicity of S. aureus. sbn genes were present in all S. aureus strains tested (and all S. aureus genome sequences) but were undetectable in any of the 13 coagulase-negative staphylococci tested, including Staphylococcus epidermidis.
Carl L. Heifetz - One of the best experts on this subject based on the ideXlab platform.
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Comparative therapeutic efficacy of clinafloxacin in a Pseudomonas aeruginosa mouse renal Abscess model.
Journal of Antimicrobial Chemotherapy, 1998Co-Authors: Martin A. Shapiro, Josephine C. Sesnie, T M Desaty, Timothy J. Griffin, Carl L. HeifetzAbstract:A deep-seated Pseudomonas aeruginosa mouse Kidney Abscess model was used to compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, with that of clinically relevant standard drugs. Following 50 mg/kg oral doses, twice daily for five consecutive days, clinafloxacin produced a 4 log decrease in mean bacterial count, the greatest decrease of all drugs tested. The same dosage regimen resulted in complete bacterial eradication in 88% of the Kidneys. No other compound produced total bacterial clearance in 50% of the Kidneys at the highest dose tested.
Patrick M. Schlievert - One of the best experts on this subject based on the ideXlab platform.
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Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury
mBio, 2013Co-Authors: Wilmara Salgado-pabón, Laura M. Breshears, Adam R. Spaulding, Joseph A. Merriman, Christopher S. Stach, Alexander R. Horswill, Marnie L. Peterson, Patrick M. SchlievertAbstract:ABSTRACT Infective endocarditis and Kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and Kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and Kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and Kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. IMPORTANCE The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763–1771, 2007). Among these infections are sepsis, infective endocarditis, and acute Kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and Kidney Abscess formation. We demonstrate that superantigens are critical in the causation of all three infections. We show that their association results from both superantigenicity and direct toxic effects on endothelial cells, the latter likely contributing to delayed endothelium healing. Our studies contribute significantly to understanding the development of these illnesses and are expected to lead to development of important therapies to treat such illnesses.
