Global distribution of α/β hydrolase family macrolide esterases in Gram-positive bacteria.

ABSTRACT: Macrolide antibiotics are vital for controlling infections in humans, animals, and agriculture, yet their effectiveness is increasingly compromised by antimicrobial resistance. Macrolide esterases (MLEs) are key mediators of macrolide resistance but have only been detected in Gram-negative bacteria, with no evidence in Gram-positive species. Here, we mined over 500 000 Gram-positive genomes and identified 8707 candidate proteins. Six representative MLEs were functionally validated, conferring resistance to 16-membered macrolides and increasing minimum inhibitory concentrations (MICs) up to 16-fold in Escherichia coli and 128-fold in Bacillus subtilis. Moreover, two exhibited broad-spectrum activity against all clinically and veterinary relevant 16-membered macrolides. Temporal analysis rev

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12704417 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature