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Trends Microbiol. 2004 Feb;12(2):66-71.

Bacterial programmed cell death systems as targets for antibiotics.

Author information

  • 1Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. hanita@cc.huji.ac.il

Abstract

Growing experimental evidence has revealed the existence of programmed cell death (PCD) systems in bacteria. Among these is the mazEF system, which is a regulable suicide module located on the chromosome of E. coli and of some other bacteria, including pathogens. Several well-known antibiotics have recently been found to cause cell death in E. coli by indirectly activating this built-in suicide module. These antibiotics belong to two groups: (i) inhibitors of transcription and/or translation; and (ii) inhibitors of folic acid metabolism resulting in thymine starvation. These data, together with the recent elucidation of the crystal structure of mazEF-directed components, hold promise for a rational chemical design of a new class of antibiotics that directly activate chromosomal suicide modules by interacting with their components. Because multi-drug resistance among bacterial pathogens is becoming more widespread, the results obtained might be useful as a basis for producing alternative drugs.

PMID:
15036322
[PubMed - indexed for MEDLINE]
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