Functional Characterization of Macrolide Esterase from Cyanobacteria and Their Potential Dissemination Risk

The global dissemination of antibiotic resistance genes (ARGs) across diverse environments has emerged as a critical challenge to public health. As essential primary producers, cyanobacteria colonize extreme and heterogeneous habitats, coexisting with gut microbiota in wastewater, marine ecosystems, and reservoirs, where they may potentiate the proliferation and transmission of ARGs under antibiotic selective pressures. In this study, five macrolide esterases (NOD-1, PTE-1, LEP-1, OCA-1, and OCB-1) of cyanobacterial origin were identified through mining of local genomic repositories. These enzymes, classified as serine-dependent alpha/beta -hydrolases, were experimentally validated through antimicrobial susceptibility testing and zone of inhibition assays to inactivate specific 16-membered macrolide antibiotics. Comparative analysis of genomic regions flanking these resistance determinants revealed the presence of mobile genetic elements (MGEs) and co-localized multidrug resistance genes, strongly suggesting the likelihood of horizontal gene transfer (HGT) within cyanobacterial populations. Such genetic mobility may exacerbate antibiotic resistance dissemination in aquatic ecosystems, underscoring the ecological risks posed by cyanobacteria as reservoirs and vectors of ARGs.