Bacterial programmed cell death systems as targets for antibiotics

Hanna Engelberg-Kulka*, Boaz Sat, Myriam Reches, Shahar Amitai, Ronen Hazan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


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.

Original languageAmerican English
Pages (from-to)66-71
Number of pages6
JournalTrends in Microbiology
Issue number2
StatePublished - Feb 2004

Bibliographical note

Funding Information:
We thank F.R. Warshaw-Dadon for critical reading of the manuscript. The research described here was supported by grant No. 215/99–2 from the Israel Science Foundation administrated by the Israel Academy of Science and Humanities.


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