Helcococcus kunzii methyltransferase Erm(47) responsible for MLSB resistance is induced by diverse ribosome-targeting...

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Helcococcus kunzii is a Gram-positive opportunistic pathogen.
• This bacterium exhibits resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics via the erm(47) gene.
• The induction mechanism of erm(47) and its atypical expression require investigation.

Purpose of the Study:

• To elucidate the induction mechanism of the erm(47) gene in H. kunzii.
• To understand the atypical expression of erm(47) conferring resistance to MLSB antibiotics.

Main Methods:

• A resistant H. kunzii clinical isolate (UCN99) was exposed to subinhibitory concentrations of various ribosome-targeting drugs.
• Mass spectrometry (MS) was employed to determine the methylation status of H. kunzii ribosomal RNA at the MLSB binding site.
• Correlation between rRNA methylation and drug resistance was analyzed.

Main Results:

• The erm(47) gene in H. kunzii encodes a monomethyltransferase.
• Erythromycin, a macrolide, induced erm(47) expression, consistent with known erm genes.
• Surprisingly, 16-membered macrolides, lincosamides, streptogramins, ketolides, chloramphenicol, and linezolid also induced erm(47) expression, all targeting the 50S ribosomal subunit.
• Spectinomycin, a 30S subunit-targeting drug, did not induce erm(47) expression.

Conclusions:

• The erm(47) leader sequence acts as a sensitive trigger for resistance induction.
• Translation of erm(47) mRNA is initiated by MLSB compounds and other 50S ribosomal subunit-targeting drugs.
• The induction of erm(47) broadens the known mechanisms of erm gene induction.