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Search: authors:"Arnold S. Bayer"

17 papers found.
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MgrA Activates Expression of Capsule Genes, but Not the α-Toxin Gene in Experimental Staphylococcus aureus Endocarditis

Background. Staphylococcus aureus produces numerous virulence factors but little is known about their in vivo regulation during an infection. Methods. The production of capsule and α-toxin, and the expression of their respective genes, cap5 and hla, were analyzed by comparing CYL11481 (derivative of Newman) and its isogenic regulatory mutants in vitro. The temporal expression of ...

Reduced Susceptibility to Host-Defense Cationic Peptides and Daptomycin Coemerge in Methicillin-Resistant Staphylococcus aureus From Daptomycin-Naive Bacteremic Patients

Background. We hypothesized that, for methicillin-resistant Staphylococcus aureus (MRSA), in vitro daptomycin susceptibility could be influenced by exposures to endogenous host defense peptides (HDPs) prior to clinical exposure to daptomycin. Methods. Two endovascular HDPs were used: thrombin-induced platelet microbicidal protein (tPMP) and human neutrophil defensin-1 (hNP-1) from ...

Factors Influencing Time to Vancomycin-Induced Clearance of Nonendocarditis Methicillin-Resistant Staphylococcus aureus Bacteremia: Role of Platelet Microbicidal Protein Killing and agr Genotypes

Background. Vancomycin susceptibility, the accessory gene global regulator (agr) genotype and function, staphylococcal cassette chromosome (SCC) mec type, and susceptibility to cationic thrombin-induced platelet microbicidal protein 1 (tPMP-1) have been individually predictive of duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This investigation evaluated ...

Disparity in the In Vitro versus In Vivo Regulation of Fibronectin-Binding Proteins by 2 Global Regulators, saeRS and sigB, in Staphylococcus aureus

Fibronectin-binding protein A plays an important role in Staphylococcus aureus endovascular infections. We characterized the sigB-saeRS-fnbA expression network with fibronectin binding in vitro and in an experimental infective endocarditis (IE) model using parental strains RN6390 and SH1000 and their respective isogenic saeRS mutants. In contrast to the in vitro data, there was no ...

Role of mgrA and sarA in Methicillin-Resistant Staphylococcus aureus Autolysis and Resistance to Cell Wall-Active Antibiotics

Background. We have previously shown the importance of mgrA and sarA in controlling autolysis of Staphylococcus aureus, with MgrA and SarA both being negative regulators of murein hydrolases.Methods. In this study, we analyzed the effects of mgrA and sarA on antibiotic-mediated lysis in vitro and on the responses to cell wall-active antibiotic therapy in an experimental ...

Virulence of Endemic Nonpigmented Northern Australian Staphylococcus aureus Clone (Clonal Complex 75, S. argenteus) Is Not Augmented by Staphyloxanthin

Staphylococcus aureus clonal complex 75 (herein referred to as S. argenteus) lacks the carotenoid pigment operon, crtOPQMN, responsible for production of the putative virulence factor, staphyloxanthin. Although a common cause of community-onset skin infections among Indigenous populations in northern Australia, this clone is infrequently isolated from hospital-based patients with ...

Enhanced Expression of dltABCD Is Associated with the Development of Daptomycin Nonsusceptibility in a Clinical Endocarditis Isolate of Staphylococcus aureus

Using isogenic clinical bloodstream Staphylococcus aureus strains from a patient with relapsing endocarditis, we investigated the transcriptional profiles of the mprF and dlt genes in the context of cell-surface charge and daptomycin nonsusceptibility. As in prior studies, a point mutation within mprF was observed in the daptomycin-nonsusceptible strain. However, neither the ...

Phenotypic and Genotypic Characteristics of Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia In Vitro and in an Experimental Endocarditis Model

Background. Persistent MRSA bacteremia (PB) represents an important subset of Staphylococcus aureus infections and correlates with poor clinical outcomes. Methods. We profiled relevant in vitro phenotypic and genotypic characteristics of MRSA isolates from 39 persons with bacteremia (21 had PB and 18 had resolving bacteremia [RB]). We also compared the intrinsic virulence and ...

Regulation of Staphylococcus aureus α-Toxin Gene (hla) Expression by agr, sarA and sae In Vitro and in Experimental Infective Endocarditis

BackgroundThe Staphylococcus aureus global regulators—agr, sarA and sae—coordinately control α-toxin gene (hla) expression in vitro. However, their relative in vivo contributions to hla expression, particularly in endovascular infections, have not been defined MethodsA plasmid-based hla-promoter:green fluorescent protein reporter system was constructed in 2 genetically related S. ...

Inhibition of Intracellular Macromolecular Synthesis in Staphylococcus aureus by Thrombin-Induced Platelet Microbicidal Proteins

Thrombin-induced platelet microbicidal proteins (tPMP-1 and tPMP-2) are believed to initiate their staphylocidal effects via cytoplasmic membrane perturbation. The aim of the present study was to investigate the role of subsequent inhibition of macromolecular synthesis in the staphylocidal mechanisms of tPMP-1 and tPMP-2 in an isogenic tPMP-susceptible and -resistant strain pair ...

Lack of Wall Teichoic Acids in Staphylococcus aureus Leads to Reduced Interactions with Endothelial Cells and to Attenuated Virulence in a Rabbit Model of Endocarditis

Wall teichoic acids (WTAs) are major surface components of gram-positive bacteria that have recently been shown to play a key role in nasal colonization by Staphylococcus aureus. In the present study, we assessed the impact that WTAs have on endovascular infections by using a WTA-deficient S. aureus mutant (ΔtagO). There were no significant differences detected between the isogenic ...

Staphylococcus aureus menD and hemB Mutants Are as Infective as the Parent Strains, but the Menadione Biosynthetic Mutant Persists within the Kidney

Small colony variants (SCVs) of Staphylococcus aureus were generated via mutations in menD or hemB yielding menadione and hemin auxotrophs, respectively, and studied in the rabbit endocarditis model. No differences in the 95% infectious dose occurred between strains with regard to seeding heart valves (∼106 cfu) or other target organs. No differences were observed between the ...

Activation and Transcriptional Interaction between agr RNAII and RNAIII in Staphylococcus aureus In Vitro and in an Experimental Endocarditis Model

This study compared the promoter activation profiles of the 2 major transcripts of the Staphylococcus aureus global regulon, agr (RNAII and RNAIII). In vitro, RNAIII activation temporally followed RNAII activation and was absent in agr mutants. In experimental endocarditis, maximal RNAII activation in vegetations occurred early, followed by progressive increases in RNAIII ...

The Oxygen- and Iron-Dependent Sigma Factor pvdS of Pseudomonas aevuginosa Is an Important Virulence Factor in Experimental Infective Endocarditis

In Pseudomonas aeruginosa, pvdS, a key oxygen (O2)-dependent locus, regulates expression of a number of virulence genes, including toxA (which encodes exotoxin A production). To define the in vivo role of differing O2 tensions on pseudomonal virulence, 2 knockout mutants, ΔpvdS and ΔtoxA, were compared with their parental strain, PA01, in rabbit aortic and tricuspid endocarditis ...

Persistent Bacteremia Due to Methicillin-Resistant Staphylococcus aureus Infection Is Associated with agr Dysfunction and Low-Level In Vitro Resistance to Thrombin-Induced Platelet Microbicidal Protein

Background. The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution. Methods. Pulsed-field gel electrophoresis (PFGE) ...

In Vitro Resistance to Thrombin-Induced Platelet Microbicidal Protein in Isolates of Staphylococcus aureus from Endocarditis Patients Correlates with an Intravascular Device Source

Platelet microbicidal proteins (PMPs) are small antimicrobial peptides secreted by mammalian platelets. In vitro resistance of Staphylococcus aureus strains to PMPs correlates with more extensive disease in experimental infective endocarditis (IE). To determine whether this same relationship exists in human S. aureus IE, we evaluated the in vitro PMP susceptibility phenotype of ...