[
International Worm Meeting,
2011]
Staphylococcus aureus (S. aureus) is a frequent colonizer of humans contributing to normal bacterial flora in nose, skin and mucosa. In addition, it is an important human pathogen causing various diseases ranging from superficial skin infections to life-threatening infections. Methicillin resistant S. aureus (MRSA) strains are rapidly spreading in the community (CA-MRSA) and is consequently becoming a more serious health threat. The capacity of S. aureus to cause this spectrum of human diseases reflects an ability to adapt to distinct microenvironments in the human body and suggests that the pathogenesis of S. aureus infection is a complex process involving a diverse array of virulence determinants that are coordinately expressed at different stages of infection. Studies have shown that virulence factors are very differently distributed among strains and are not always regulated in the same way, reflecting the ability of S. aureus to adapt and survive in different environmental niches and resist antibiotic treatment. C. elegans has previously been established as a model host for the study of S. aureus pathogenesis and CA-MRSA strains are capable of killing C. elegans[1]. We have screened thirty clinical MRSA isolates and found that in terms of pathogenicity they can be divided into separate classes. Using these classes we wish to identify new virulence markers and novel immunity pathways activated in response to S. aureus infection. We are particularly interested in evaluate virulence determinants during colonization versus infection and establishing their clinical relevance in humans. Inactivation of some S-M checkpoint proteins increase stress resistance and lifespan of C. elegans[2]. Since there may exist a potential correlation between stress response and immune function we are studying the role of checkpoint proteins to S. aureus exposure. We have identified several novel genes with potential checkpoint function which increase lifespan and thermotolerance. We find that that mutation of one of these, the transmembrane protein NDG-4, also confers resistance towards S. aureus infection. Epistasis analysis reveals that increased tolerance towards S. aureus infection is partially dependent on insulin signaling but that another unidentified component is involved as well. 1. Sifri, C.D., et al. 2003. 71(4): p. 2208-17. 2. Olsen, A., M.C. Vantipalli, and G.J. Lithgow. Science, 2006. 312(5778): p. 1381-5.