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 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.
Engelberg-Kulka
Hanna
H
Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. hanita@cc.huji.ac.il
Sat
Boaz
B
Reches
Myriam
M
Amitai
Shahar
S
Hazan
Ronen
R
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
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