STAPHYLOCOCCUS-AUREUS GENETIC-LOCI IMPACTING GROWTH AND SURVIVAL IN MULTIPLE INFECTION ENVIRONMENTS

The Gram-positive bacterium Staphylococcus aureus infects diverse tiss ues and causes a wide spectrum of diseases, suggesting that it possess es a repertoire of distinct molecular mechanisms promoting bacterial s urvival in disparate in vivo environments. Signature-tag transposon mu tagenesis screening of a 1520-member library identified numerous S. au reus genetic loci affecting growth and survival in four complementary animal infection models including mouse abscess, bacteraemia and wound and rabbit endocarditis. Of a total of 237 in vivo attenuated mutants identified by the murine models, less than 10% showed attenuation in all three models, emphasizing the advantage of screening in diverse di sease environments. The largest gene class identified by these analyse s encoded peptide and amino acid transporters, some of which were impo rtant for S. aureus survival in all animal infection models tested. Th e identification of staphylococcal loci affecting growth, persistence and virulence in multiple tissue environments provides insight into th e complexities of human infection and on the molecular mechanisms that could be targeted by new antibacterial therapies.