Bacterial programmed cell death systems as targets for antibiotics

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...

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Bibliographic Details
Published in:Trends in microbiology (Regular ed.) 2004-02, Vol.12 (2), p.66-71
Main Authors: Engelberg-Kulka, Hanna, Sat, Boaz, Reches, Myriam, Amitai, Shahar, Hazan, Ronen
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Apoptosis
Bacteria - drug effects
Bacterial Physiological Phenomena
Chloramphenicol - pharmacology
DNA-Binding Proteins - physiology
Endoribonucleases
Escherichia coli
Escherichia coli - drug effects
Escherichia coli - physiology
Escherichia coli Proteins - physiology
Protein Biosynthesis - drug effects
Rifampin - pharmacology
Sulfonamides - pharmacology
Thymine - metabolism
Transcription, Genetic - drug effects
Trimethoprim - pharmacology
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Summary: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.
ISSN:0966-842X
1878-4380
DOI:10.1016/j.tim.2003.12.008