| The Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis account for the majority of hospital acquired infections and place a large burden on the health care system. Recently the nematode Caenorhabditis elegans has emerged as a simple host in which to study host pathogen interactions from both the perspective of bacterial virulence and host immunity. Under defined laboratory conditions, S. aureus and S. epidermidis infect and kill C. elegans. S. aureus causes a transient infection with intestinal accumulation that is dependent both on previously described mammalian virulence factors, as well as novel factors identified in a forward genetic screen. In contrast, S. epidermidis causes a persistent infection involving biofilm formation, which appears to protect S. epidermidis from immune effectors downstream of a C. elegans nsy-1/sek-1/pmk-1 MAP kinase cascade, a key component of the C. elegans immune response. C. elegans strains harboring mutations in the DAF-2 signaling pathway were examined and found to be resistant to pathogens. Although daf-2, age-1 , and pdk-1 mutants were both pathogen resistant and long-lived, mutations in the downstream AGC kinase components akt-1, akt-2, and sgk-1 exhibited distinct longevity and pathogen resistance behaviors. The identification of mutants in a forward genetic screen that were pathogen resistant but had normal life-spans further demonstrated that longevity and pathogen resistance are distinct processes. Thus, the development of the C. elegans-Staphylococcus model system represents an important experimental advance for better understanding pathogen-host relationships. |
