A Novel Chemical Biology Approach for Mapping of Polymyxin Lipopeptide Antibody Binding Epitopes
Tony Velkov, Bo Yun, Elena K Schneider, Mohammad AK Azad, Olan Dolezal, Faye C Morris, Roger L Nation, Jiping Wang, Ke Chen, Heidi H Yu, Lv Wang, Philip E Thompson, Kade D Roberts, Jian Li
ACS INFECTIOUS DISEASES | AMER CHEMICAL SOC | Published : 2016
Polymyxins B and E (i.e., colistin) are a family of naturally occurring lipopeptide antibiotics that are our last line of defense against multidrug resistant (MDR) Gram-negative pathogens. Unfortunately, nephrotoxicity is a dose-limiting factor for polymyxins that limits their clinical utility. Our recent studies demonstrate that polymyxin-induced nephrotoxicity is a result of their extensive accumulation in renal tubular cells. The design and development of safer, novel polymyxin lipopeptides is hampered by our limited understanding of their complex structure-nephrotoxicity relationships. This is the first study to employ a novel targeted chemical biology approach to map the polymyxin recog..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
J.L., T.V., RL.N., P.E.T., and K.D.R are supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI098771), and J.L. and T.V. are also supported by R01 AI111965. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. J.L. is an Australian NHMRC Senior Research Fellow. T.V. is an Australian NHMRC Industry Career Development Research Fellow.