This Harvard-wide Program on Antibiotic Resistance (HPAR) proposal outlines the design and function of a novel, interdisciplinary, collaborative partnership to develop and test new validated lead compounds for changing the paradigms for treatment of multidrug resistant MRSA, VRE and now VRSA infections. Although discovery and delivery of novel and promising new compounds to the development pipeline is a major overall goal, because this is an academic effort, adding to the base of scientific knowledge that underpins the development of inhibitors for these pathogens;the understanding of resistance, and development of novel new tools for studying host-pathogen interactions and multidrug resistant pathogens are also major goals. This project is being proposed by an accomplished group of scientists with extensive experience in the biochemistry of cell wall biosynthesis and use of that information to design screens and new inhibitors;the molecular biology of model host systems and the use of those systems in novel ways for screening compounds that block the ability of bacteria to harm the host;the biology and molecular genetics of biofilm formation in model systems and the use of that information to identify biofilm disrupting agents;the pathogenesis, genetics and antibiotic resistance of enterococci;and the pathogenesis, molecular biology and clinical treatment of infection caused by multidrug resistant staphylococci. This scientific expertise is complemented by administrative experience that includes service as university Vice President for Research, and President and CEO of a research institute. The goal of the HPAR Administrative Core is to create a cohesive and well functioning whole that is greater than the sum of the individual projects.
The Specific Aims of the Administrative Core are to 1) Provide program management and oversight, 2) Facilitate interactions between participants from the various components of Harvard University, 3) Provide critical infrastructure for fiscal management of the program;4) Provide connectivity to and leverage from other Harvard-wide initiatives;and 5) Provide a single point of contact and active coordination for on-going communication with NIAID and the Program Officer, and other NIAID initiatives.
MRSA infections are common, often invasive and life threating. VRE are leading causes of hospital acquired infection. VRE now have donated vancomycin resistance to MRSA, creating VRSA refractor to this last line antibiotic. The administrative core will assure the smooth operation of this PPG, and will insure that the products generated are much greater than the sum of its parts.
|Truong-Bolduc, Q C; Wang, Y; Chen, C et al. (2017) Transcriptional Regulator TetR21 Controls the Expression of the Staphylococcus aureus LmrS Efflux Pump. Antimicrob Agents Chemother 61:|
|Gwisai, Tinotenda; Hollingsworth, Nisha Rosita; Cowles, Sarah et al. (2017) Repurposing niclosamide as a versatile antimicrobial surface coating against device-associated, hospital-acquired bacterial infections. Biomed Mater 12:045010|
|Truong-Bolduc, Q C; Khan, N S; Vyas, J M et al. (2017) Tet38 Efflux Pump Affects Staphylococcus aureus Internalization by Epithelial Cells through Interaction with CD36 and Contributes to Bacterial Escape from Acidic and Nonacidic Phagolysosomes. Infect Immun 85:|
|Ibberson, Carolyn B; Stacy, Apollo; Fleming, Derek et al. (2017) Co-infecting microorganisms dramatically alter pathogen gene essentiality during polymicrobial infection. Nat Microbiol 2:17079|
|Zheng, Zhaojun; Tharmalingam, Nagendran; Liu, Qingzhong et al. (2017) Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa. Antimicrob Agents Chemother 61:|
|Saavedra, José T; Schwartzman, Julia A; Gilmore, Michael S (2017) Mapping Transposon Insertions in Bacterial Genomes by Arbitrarily Primed PCR. Curr Protoc Mol Biol 118:15.15.1-15.15.15|
|Rajagopal, Mithila; Walker, Suzanne (2017) Envelope Structures of Gram-Positive Bacteria. Curr Top Microbiol Immunol 404:1-44|
|Matano, Leigh M; Morris, Heidi G; Hesser, Anthony R et al. (2017) Antibiotic That Inhibits the ATPase Activity of an ATP-Binding Cassette Transporter by Binding to a Remote Extracellular Site. J Am Chem Soc 139:10597-10600|
|Lebreton, François; Manson, Abigail L; Saavedra, Jose T et al. (2017) Tracing the Enterococci from Paleozoic Origins to the Hospital. Cell 169:849-861.e13|
|Nakaminami, Hidemasa; Chen, Chunhui; Truong-Bolduc, Que Chi et al. (2017) Efflux Transporter of Siderophore Staphyloferrin A in Staphylococcus aureus Contributes to Bacterial Fitness in Abscesses and Epithelial Cells. Infect Immun 85:|
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