Macrolide resistance due to erm(55).

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Antimicrobial resistance (AMR) is a significant global health challenge.
• The erm(55) gene, identified in macrolide-resistant Mycobacterium chelonae, was predicted to be a ribosomal methyltransferase but its resistance role was unconfirmed.
• Three distinct alleles of erm(55) have been documented: plasmid-borne erm(55)P, transposon-associated erm(55)T, and chromosomal erm(55)C.

Purpose of the Study:

• To experimentally validate the role of the three erm(55) variants as determinants of macrolide resistance.
• To assess the degree to which each erm(55) variant reduces susceptibility to clinically relevant macrolides.
• To provide critical data for antimicrobial resistance surveillance and the development of new therapeutic strategies.

Main Methods:

• Expression of the three erm(55) alleles (erm(55)P, erm(55)T, and erm(55)C) in a macrolide-susceptible Escherichia coli strain.
• Phenotypic testing of engineered E. coli strains to determine macrolide susceptibility.
• Comparative analysis of resistance conferred by each erm(55) variant.

Main Results:

• All three erm(55) variants, when expressed in E. coli, conferred resistance to the macrolide antibiotics azithromycin and clarithromycin.
• The study demonstrated that erm(55) is a functional macrolide resistance gene.
• Each variant exhibited unique levels of reduced susceptibility to clinically relevant macrolides, highlighting functional diversity.

Conclusions:

• The erm(55) gene and its variants are confirmed determinants of macrolide resistance.
• This research provides essential experimental evidence for the role of erm(55) in antimicrobial resistance.
• Findings contribute to a better understanding of macrolide resistance mechanisms in bacteria, aiding surveillance efforts.