Antibiotic Resistance Mechanism in Pseudomonas aeruginosa

Paul Hergenrother, University of Illinois at Urbana-Champaign

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Po-Chao Wen, Muyun Lihan, Zhiyu Zhao, Archit Vasan, Nandan Haloi, Ali Rasouli, Defne Gorgun, Paul Hergenrother, Hale Hasdemir, Julio Maia

Bacterial resistance to antibiotics has long been a serious threat to the public health. Effective antibiotics for Gram-negative bacteria are especially limited due to the intrinsic resistance provided by their outer membrane (OM). The Hergenrother group has been developing novel broad-spectrum antibiotics by chemically modifying known antibiotics working against Gram-positive bacteria to improve their OM permeability among Gram-negative bacteria.  Although the approach has proven successful, the improved antibiotic compound seemed particularly weak against the Gram-negative bacterium Pseudonomas aeruginosa. This differential behavior is likely related to the fact that P. aeruginosa has a unique OM structure that is drastically different from the previously studied Escherichia coli model system, both with regard to the chemical compositions of the mem- branes and with respect to their unique OM porins that provide permeability to small molecules. The research in this proposal aims to study the effect of the chemical composition of the outermost layer of the OM to the porin accessibility of drugs, and the impact of key structural details of the P. aeruginosa porin OprD on antibiotic permeability.