The Harvard-wide Program on Antibiotic Resistance (HPAR) represents a tightly knit set of collaborative research projects to address one of the leading public health issues in the US -- the spread of antibiotic resistant Staphylococcus aureus as a leading cause of serious infection in the community as well as in hospitals. Advanced by a cohesive, multi-disciplinary group of clinical, basic and translational scientists, the theme of this Program Project proposal is to """"""""Derive new approaches for combating MRSA infection, and limiting the development and spread of antibiotic resistance."""""""" The expertise of this team ranges from high throughput screening/follow up chemistry, biochemistry, molecular biology/genetics, and molecular pathogenesis to clinical microbiology. The investigators are all among leaders in their respective fields, and bring the perspectives and assets of institutions spanning Harvard University - Massachusetts General Hospital, Harvard Medical School, Harvard College, and Schepens Eye Research Institute - to bear. The goal of this Program Project is to capitalize on multi-disciplinary perspectives, and to take both hypothesis driven and discovery approaches, to advance a better understanding of the development (Subproject 1: Hooper) and spread (Subproject 2: Gilmore) of antibiotic resistance in S. aureus;and to identify novel compounds, targets and pathways to compromise the microbe in its interaction with the host (Subproject 3: walker;Subproject 4: Ausubel/Mylonakis [both in collaboration with Hooper and Gilmore]). The entire project is held together, with each project being leveraged by the others, by the Administrative Core (Core A), which will be led by a P1 with considerable administrative experience. The HPAR is specifically designed to synergize and leverage internal and external initiatives, including the Harvard-wide Microbial sciences Initiative and the Catalyst Clinical and Translational Science Center, and the NIAID NARSA program. ran o'"""""""". =?. 7""""""""o vii '-? FD'
Staphylococcusaureus,especiallymethicillinresistant(MRSA)strains,haveemergedasleadingcauses oflifethreateninginfectioninthehospitalandinthecommunity.WhiletheMRSAproblemisalarming, ithasbecomecriticalastheresultoftheintroductionoffrankvancomycinresistance.Therenowhave been9welldocumentedcasesoftransferofvancomycinresistancefromenterococcitoMRSAinthe US.ThisProgramProjectisdesignedtoidentifynewcompoundsforcombatingS.aureusinfectionand fortifyingthehostimmuneresponse,thatideallywillnotbecompromisedbyexistingbacterialefflux systemsoracquiredresistances. 6
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