New rules for Gram-negative antibiotics

Abstract

In the fight against pathogenic bacteria, Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa are particularly challenging foes. These microbes don’t respond to many common antibiotics, and no new drug active against Gram-negative bacteria has been approved in nearly a half century. Part of the difficulty in developing such antibiotics is that molecules have a hard time slipping inside Gram-negative bacteria. The bacteria have two cell membranes, and compounds must also navigate porin protein channels to enter. A new study outlines a systematic approach to ferreting out properties compounds must have to penetrate and accumulate in Gram-negative bacteria. The authors demonstrated the power of the approach by converting an antibiotic that previously couldn’t enter Gram-negative bacteria into one that can. Paul J. Hergenrother and coworkers at the University of Illinois, Urbana-Champaign, used liquid chromatography and tandem mass spectrometry to assess the ability of compounds to ente...