Molecular mechanisms of immune evasion in Staphylococcus aureus

National Institute Of Allergy And Infectious Diseases

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Abstract

In the past year, we have focussed on mechanisms that determine the interaction of staphylococci with innate host defense. We have identified cytolytic peptides as main weapons of Staphylococcus aureus immune evasion. [unreadable] [unreadable] In our main effort in the past year, we have shifted our research interest to methicillin-resistant Staphylococcus aureus (MRSA), which remain a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings. In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room. It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. We found a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study has revealed a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA.