MICROBIOLOGY: Designed to Penetrate

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Science  26 Jul 2002:
Vol. 297, Issue 5581, pp. 481b
DOI: 10.1126/science.297.5581.481b

One factor contributing to the innate resistance of bacteria to some antibiotics is membrane permeability. The general diffusion porin, OmpF, governs the influx of various molecules, including beta-lactam antibiotics, through the outer bacterial membrane. In the periplasmic space, these antibiotics inhibit bacterial cell wall synthesis. Nestorovich et al. put pure, intact, and functional E. coli OmpF in artificial lipid bilayers and showed that a current between the chambers made by the bilayer was interrupted when ampicillin was added. Earlier observations on OmpF by Simonet et al. showed that mutations in the third beta-sheet loop of OmpF, which penetrates the channel of the porin, result in resistance to ampicillin—the drug of choice for E. coli disease. Nestorovich's structural modeling studies show that the zwitterionic ampicillin “docks” at the midway constriction made by loop 3, because of the complementary electrostatic charges in the walls of the pore, thus blocking current flow. In some unknown way, the docking helps to speed up the transport of the antibiotic into the periplasmic space. Now the bilayer-OmpF system can be used in high-throughput screening devices to help predict the antibiotic potency of synthetic beta-lactam molecules. — CA

Proc. Natl. Acad. Sci. U.S.A. 99, 9789 (2002); Antimicrob. Agents Chemother. 44, 311 (2000).

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