title: Bacterial programmed cell death systems as targets for antibiotics.
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.
authors.affiliation: Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. hanita@cc.huji.ac.il
authors.forename: Hanna
authors.initials: H
authors.lastname: Engelberg-Kulka
authors.forename: Boaz
authors.initials: B
authors.lastname: Sat
authors.forename: Myriam
authors.initials: M
authors.lastname: Reches
authors.forename: Shahar
authors.initials: S
authors.lastname: Amitai
authors.forename: Ronen
authors.initials: R
authors.lastname: Hazan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis; D001419:Bacteria / Q000187:drug effects; D018407:Bacterial Physiological Phenomena; D002701:Chloramphenicol / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D004722:Endoribonucleases; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology; D014176:Protein Biosynthesis / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013941:Thymine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014295:Trimethoprim / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422954:MazE protein, E coli; C422955:MazF protein, E coli; D013449:Sulfonamides; D002701:Chloramphenicol; D014295:Trimethoprim; D004722:Endoribonucleases; D013941:Thymine; D012293:Rifampin