Abstract
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes substantial skin and soft tissue infections annually in the United States and expresses numerous virulence factors, including a family of toxins known as the staphylococcal superantigen-like (SSL) proteins. Many of the SSL protein structures have been determined and implicated in immune system avoidance, but the full scope that these proteins play in different infection contexts remains unknown and continues to warrant investigation. Analysis of ssl gene regulation may provide valuable information related to the function of these proteins. To determine the transcriptional regulation of the ssl1 gene of CA-MRSA strain MW2, an ssl1 promoter::lux fusion was constructed and transformed into S. aureus strains RN6390 and Newman. Resulting strains were grown in a defined minimal medium (DSM) broth and nutrient-rich brain-heart infusion (BHI) broth and expression was determined by luminescence. Transcription of ssl1 was up-regulated and occurred earlier during growth in DSM broth compared to BHI broth suggesting expression is regulated by nutrient availability. RN6390 and Newman strains containing the ssl1::lux fusion were also used to analyze regulation in vivo using a mouse abscess model of infection. A marked increase in ssl1 transcription occurred early during infection, suggesting SSL1 is important during early stages of infection, perhaps to avoid the immune system.
Highlights
IntroductionStaphylococcus aureus is one of the most clinically significant human pathogens and is responsible for a wide variety of infections, ranging from skin and soft tissue infections (e.g., boils, furuncles, etc.) to more invasive diseases (e.g., bacteremia, endocarditis, pneumonia, toxic shock syndrome, and necrotizing fasciitis) [1]
Staphylococcus aureus is one of the most clinically significant human pathogens and is responsible for a wide variety of infections, ranging from skin and soft tissue infections to more invasive diseases [1]
We demonstrate that ssl1 expression occurs early in a murine abscess model of infection, consistent with the hypothesis that the staphylococcal superantigen-like (SSL) proteins are important for immune avoidance
Summary
Staphylococcus aureus is one of the most clinically significant human pathogens and is responsible for a wide variety of infections, ranging from skin and soft tissue infections (e.g., boils, furuncles, etc.) to more invasive diseases (e.g., bacteremia, endocarditis, pneumonia, toxic shock syndrome, and necrotizing fasciitis) [1]. The disease-causing ability of CA-MRSA can be attributed to an impressive list of virulence factors Many of these factors are shared with all S. aureus strains and include lipases, nucleases, proteases, hyaluronidase, collagenase, exfoliative toxins, leukocidins, and four hemolysins [4]. Along with these virulence factors, CA-MRSA strains have been shown to carry various novel putative toxin genes, including staphylococcal enterotoxin homologues (seg, sel, sec, and sek2), bsa (a bacteriocin), cna, ear, and lpl10 [5,6]. Most of these novel toxins have yet to be fully characterized but may represent a repertoire of factors necessary for the disease-causing capability of MRSA in the community
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