MccE provides resistance to protein synthesis inhibitor microcin C by acetylating the processed form of the antibiotic.
The heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. McC is excreted from producing cells by the MccC transporter. The residual McC that remains in the producing cell can be processed by cellular aminopeptidases with the release of a non-hydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase. Accumulation of processed McC inside producing cells should therefore lead to translation inhibition and cessation of growth. Here, we show that a product of another gene of the McC biosynthetic cluster, mccE, acetylates processed McC and converts it into a non-toxic compound. MccE also makes Escherichia coli resistant to albomycin, a Trojan horse inhibitor unrelated to McC that, upon processing, gives rise to a serine coupled to a thioxylofuranosyl pyrimidine, an inhibitor of seryl-tRNA synthetase. We speculate that MccE and related cellular acetyltransferases of the Rim family may detoxify various aminoacyl-nucleotides, either exogenous or those generated inside the cell.
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia.
Maria
M
Novikova
Teymur
T
Kazakov
Gaston H
GH
Vondenhoff
Ekaterina
E
Semenova
Jef
J
Rozenski
Anastasija
A
Metlytskaya
Inna
I
Zukher
Anton
A
Tikhonov
Arthur
A
Van Aerschot
Konstantin
K
Severinov
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001226:Aspartate-tRNA Ligase / Q000037:antagonists & inhibitors; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005291:Ferrichrome / Q000031:analogs & derivatives / Q000494:pharmacology; D005810:Multigene Family / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D029968:Escherichia coli Proteins; C020411:microcin; D005291:Ferrichrome; C052755:aspartyl adenylate; C015657:albomycin; D001224:Aspartic Acid; D000249:Adenosine Monophosphate; D000123:Acetyltransferases; D001226:Aspartate-tRNA Ligase