Functional analysis of a novel macrolide-lincosamide resistance gene erm(57) in Cutibacterium avidum

Cutibacterium species, including Cutibacterium avidum, Cutibacterium granulosum and Cutibacterium acnes are commensal skin bacteria. The latter exacerbates acne vulgaris. In the past decades, high antimicrobial use for the treatment of acne has led to the spread of macrolide- and lincosamide-resistant, particularly clindamycin-resistant, strains. C. avidum has been reported to show higher resistance rates than C. acnes. The known mechanisms of macrolide resistance in Cutibacterium species includes either mutations in 23S rRNA encoding gene or the acquisition of methyltransferase genes, such as erm(X) and erm(50). This study analysed the resistance mechanisms of C. avidum, a commensal skin species that is occasionally isolated from acne lesions. This study focused on strains lacking known macrolide-lincosamide resistance determinants.

The antimicrobial susceptibility of 50 C. avidum strains isolated from facial acne pustules between 2013 and 2020 was evaluated by determining MIC values. Whole-genome sequencing was used to identify the putative resistance factors. The candidate gene was cloned into Escherichia coli for functional analysis, and its amino acid sequence was compared with that of previously reported Erm proteins.

Approximately 90% of C. avidum strains exhibited resistance to macrolides and clindamycin. Two of these strains lacked known resistance factors. Whole-genome sequence analysis revealed the presence of a methyltransferase-encoding gene. Introducing this gene into E. coli conferred resistance to macrolides, confirming its function. The protein with the highest similarity to Erm(38), but <79% identity, was therefore designated as Erm(57). Unlike erm(X) and erm(50), erm(57) was not transmitted horizontally.

This study identified erm(57) as a novel non-transmissible macrolide-lincosamide resistance gene in C. avidum.