Resistance to enediyne antitumor antibiotics by CalC self-sacrifice.
Antibiotic self-resistance mechanisms, which include drug elimination, drug modification, target modification, and drug sequestration, contribute substantially to the growing problem of antibiotic resistance among pathogenic bacteria. Enediynes are among the most potent naturally occurring antibiotics, yet the mechanism of resistance to these toxins has remained a mystery. We characterize an enediyne self-resistance protein that reveals a self-sacrificing paradigm for resistance to highly reactive antibiotics, and thus another opportunity for nonpathogenic or pathogenic bacteria to evade extremely potent small molecules.
Biggins
John B
JB
Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
Onwueme
Kenolisa C
KC
Thorson
Jon S
JS
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D053281:Enediynes; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D053281:Enediynes; D008667:Metalloproteins; C055955:calicheamicin gamma(1)I; D004247:DNA; C047543:esperamicin A1