Helicobacter pylori is a human gastric pathogen that is highly diverse and relies on natural transformation to acquire antimicrobial resistance (AMR) genes, adapt to the human host and promote lifelong colonisation. However, we have limited understanding of factors that influence the efficiency of H. pylori to naturally acquire DNA-encoding (AMR) and promote genetic diversity. Bacterial membrane vesicles (BMVs) have emerged as a novel mechanism used to package DNA, mediate horizontal gene transfer (HGT) and disseminate AMR within and between bacterial species. However, the contribution of BMVs to the development of AMR within H. pylori remains unknown and was examined as part of this study.
BMVs were isolated from H. pylori strains harbouring AMR genes within the genome. The size and morphology of BMVs isolated from each strain were examined by transmission electron microscopy and nanoparticle tracking analysis, and DNA associated with BMVs was quantified. Natural transformation of H. pylori isolates using BMVs isolated from H. pylori strains encoding AMR resulted in the generation of antimicrobial-resistant H. pylori transformants. In addition, BMVs showed varying strain-specific efficiency in transforming H. pylori compared to genomic DNA alone. Furthermore, the bacterial growth conditions used to generate BMVs are currently being investigated using a range of molecular and imaging techniques to determine their morphology, composition and impact on the delivery of AMR genes into recipient bacterial cells.
Collectively, these findings reveal a novel mechanism whereby H. pylori can acquire AMR mediated by BMVs. Given the abundance of BMVs in clinical and environmental settings, they link agriculture, the environment and human health and may contribute to the increased emergence of antimicrobial-resistant pathogens. Further understanding of mechanisms whereby BMVs mediate HGT will advance knowledge regarding AMR transmission within and between microbial communities, and increase our understanding of the proportion of clinically relevant AMR dissemination attributable to BMVs.