Protein A is a virulence factor in Staphylococcus aureus arthritis and septic death

Palmqvist, Niklas; Foster, Timothy J.; Tarkowski, Andrzej; Josefsson, Elisabet

doi:10.1006/mpat.2002.0533

Cited by 157 publications

(107 citation statements)

References 52 publications

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“…This is consistent with our earlier report demonstrating increased expression of spa in UAMS-1 relative to RN6390 by Northern blotting . Spa production has been associated with increased virulence and modulation of the immune response (Palmqvist et al, 2002(Palmqvist et al, , 2005Gomez et al, 2004;Goodyear & Silverman, 2004). This suggests that the relative levels of spa expression may at least partially account for our previous observation that UAMS-1 is more virulent than RN6390 in our animal models of musculoskeletal infection (Blevins et al, 2003).…”

Section: Resultsmentioning

confidence: 55%

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

Cassat

Dunman

Murphy³

et al. 2006

Microbiology

146

157

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The production of Staphylococcus aureus virulence factors is under the control of complex regulatory circuits. Most studies aimed at defining these regulatory networks have focused on derivatives of the strain NCTC 8325, most notably RN6390. However, all NCTC 8325 derivatives, including RN6390, possess an 11 bp deletion in rsbU. This deletion renders NCTC 8325 derivatives naturally sigma-factor-B deficient. Recent studies have shown that RN6390 is also deficient, in comparison to clinical isolates, with respect to biofilm formation, a process which is important for both pathogenesis and antimicrobial resistance. Based on these considerations, the authors carried out genome-scale transcriptional profiling, comparing RN6390 with the virulent rsbU-positive clinical isolate UAMS-1. The results revealed significant genome-wide differences in expression patterns between RN6390 and UAMS-1, and suggested that the overall transcriptional profile of UAMS-1 is geared toward expression of factors that promote colonization and biofilm formation. In contrast, the transcriptional profile of RN6390 was heavily influenced by RNAIII expression, resulting in a phenotype characterized by increased production of exoproteins, and decreased capacity to form a biofilm. The greater influence of agr in RN6390 relative to UAMS-1 was also evident when the transcriptional profile of UAMS-1 was compared with that of its isogenic sarA and agr mutants. Specifically, the results indicate that, in contrast to NCTC 8325 derivatives, agr plays a limited role in overall regulation of gene expression in UAMS-1, when compared with sarA. Furthermore, by defining the sarA regulon in a biofilm-positive clinical isolate, and comparing the results with transcriptional profiling experiments defining biofilm-associated gene expression patterns in the same strain, the authors identified a sarA-regulated operon (alsSD) that is also induced in biofilms, and demonstrated that mutation of alsSD results in reduced capacity to form a biofilm.

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Section: Resultsmentioning

confidence: 55%

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

Cassat

Dunman

Murphy³

et al. 2006

Microbiology

146

157

View full text Add to dashboard Cite

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“…Only two strains actually failed to give a positive result, indicating that these strains were true spa-deficient strains. Although spa has been shown to be an important virulence factor in the pathogenesis of S. aureus infections (29), the two spa-deficient strains were isolated from patients with severe S. aureus-related infections, indicating that the strains were still virulent and invasive in spite of being spa deficient. Peacock et al, in their study of 334 S. aureus carriage and invasive isolates, detected the presence of spa in 90 and 94% of strains, respectively, by PCR analysis (30).…”

Section: Discussionmentioning

confidence: 93%

Non- spa -Typeable Clinical Staphylococcus aureus Strains Are Naturally Occurring Protein A Mutants

et al. 2009

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Staphylococcus aureus is a major human pathogen responsible for increasing the prevalence of communityand hospital-acquired infections. Protein A (SpA) is a key virulence factor of S. aureus and is highly conserved. Sequencing of the variable-number tandem-repeat region of SpA (spa typing) provides a rapid and reliable method for epidemiological studies. Rarely, non-spa-typeable S. aureus strains are encountered. The reason for this is not known. In this study, we characterized eight non-spa-typeable bacteremia isolates. Sequencing of the entire spa locus was successful for five strains and revealed various mutations of spa, all of which included a deletion of immunoglobulin G binding domain C, in which the upper primer for spa typing is located, while two strains were truly spa negative. This is the first report demonstrating that nontypeability of S. aureus by spa sequencing is due either to mutation or to a true deficiency of spa.

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“…It can interact with several host components (39) and is a virulence factor in septic arthritis (38). The polymorphic X region in the spa gene has proved to be sufficiently stable for typing, with discriminatory power comparable to that of phage typing, PFGE, and restriction fragment length polymorphism typing (14).…”

Section: Discussionmentioning

confidence: 99%

Molecular and Phenotypic Characteristics of Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus Isolates from Patients with Septic Arthritis

et al. 2009

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Staphylococcus aureus is one of the most common pathogens in community-and hospital-associated infections and frequently causes severe and intractable infections in osteoarticular tissues. S. aureus isolates that are resistant to methicillin (meticillin) (MRSA isolates) and intermediately resistant to vancomycin (VISA isolates) have emerged. In this report, we described two patients, one female and one male, diagnosed with septic arthritis due to S. aureus infections. A total of 13 MRSA isolates were obtained from these two patients. All but one isolate belonged to the VISA group. All seven isolates from the female patient were determined to be community associated, multilocus sequence type (MLST) 59, and staphylococcal cassette chromosome mecA (SCCmec) type IV; had direct repeat units (DRUs) of nine repeats; were spa type t437; and were susceptible to sulfa and quinolone antibiotics. The other six isolates, from the male patient, were determined to be hospital associated, MLST 239, and SCCmec type III; had DRUs of 14 repeats; were spa type t037; and were resistant to sulfa and quinolone antibiotics. All 13 MRSA isolates were in agr group I, were pvl negative, and showed no evidence of any association between vancomycin resistance and autolysis.

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Protein A is a virulence factor in Staphylococcus aureus arthritis and septic death

Cited by 157 publications

References 52 publications

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

Non- spa -Typeable Clinical Staphylococcus aureus Strains Are Naturally Occurring Protein A Mutants

Molecular and Phenotypic Characteristics of Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus Isolates from Patients with Septic Arthritis

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