The RimL transacetylase provides resistance to translation inhibitor microcin C

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Microcin C (McC) is a peptide-nucleotide antibiotic produced by Escherichia coli.
• Processed McC releases a toxic aspartyl-adenylate analog inhibiting aspartyl-tRNA synthetase.
• The mccE gene product acetylates processed McC, conferring nontoxicity.

Purpose of the Study:

• To investigate the role of E. coli acetyltransferases, specifically RimL, in resistance to McC and related toxic compounds.
• To identify novel bacterial defense mechanisms against aminoacyl adenylates.

Main Methods:

• Comparative analysis of acetyltransferase activity (RimI, RimJ, RimL, YhhY) against processed McC and toxic aminoacyl adenylates.
• Assessment of antibiotic resistance in E. coli strains with altered expression of RimL and YhhY.
• Identification of natural substrates for RimL.

Main Results:

• E. coli RimL confers resistance to McC and toxic nonhydrolyzable aminoacyl adenylates by acetylating processed McC.
• Ribosomal protein L12 is identified as a natural substrate for RimL, alongside processed McC.
• Overproduced RimL also confers resistance to albomycin, an antibiotic targeting seryl-tRNA synthetase.
• E. coli YhhY detoxifies aminoacyl adenylates but not processed McC.

Conclusions:

• RimL and YhhY are crucial for bacterial defense against toxic aminoacyl nucleotides, both exogenous and endogenous.
• RimL's acetylation activity extends beyond ribosomal proteins to include processed McC, highlighting its broader protective role.
• The study reveals a novel detoxification pathway involving RimL and YhhY, expanding our understanding of bacterial antibiotic resistance.