Outer Membrane Vesicles as a Potential Pathway for Antibiotic Resistance Transfer between Cyanobacteria and Bacteria

Abstract

Abstract Antibiotic resistance genes (ARGs) have profoundly exacerbated environmental risks to public health, evolving into a pressing ecological dilemma. Distinct from traditional pathways, outer membrane vesicles (OMVs) are emerging as important vectors for horizontal gene transfer (HGT) in aquatic environments, yet their role in inter-phylum ARG dissemination remains unclear. In this study, we demonstrate that OMVs mediate bidirectional HGT of ARGs between the cyanobacterium Synechocystis sp. PCC 6803 and Escherichia coli DH5α. Co-incubation experiments confirmed that OMVs derived from either strain could associate with the other, accompanied by successful functional expression of transferred resistance genes. In simulated aquatic environmental conditions, OMVs supplementation increased HGT frequency by 1.49–2.27 folds compared to the control group on day 5. Metagenomic analysis further revealed that OMVs carrying resistance genes induced subtle shifts in coastal microbial community composition. Our findings establish OMVs as mobile genetic packages that enable ARGs exchange between cyanobacteria and heterotrophic bacteria, highlighting a previously overlooked pathway for environmental dissemination of ARGs and providing a theoretical basis for mitigating antibiotic resistance risks in aquatic ecosystems.