Hidden Threats: How Small Cryptic Plasmids Drive Antibiotic Resistance Evolution ?

Plasmids are autonomously replicating extrachromosomal elements that often encode traits contributing to bacterial fitness. Large low-copy-number plasmids in Enterobacteriaceae frequently carry virulence and multi-antibiotic resistance genes. However, many bacteria also harbor small cryptic plasmids without obvious beneficial functions for their hosts.

Recently, we identified a novel mechanism generating transient antibiotic resistance through transposition of resistance genes onto small cryptic plasmids, followed by an antibiotic-selected increase in plasmid copy number. This prevalent mechanism was observed across various clinical isolates and antibiotic classes.

Importantly, the high instability and fitness costs associated with such transient resistance result in a rapid reversion to antibiotic susceptibility when antibiotics are removed, a phenomenon largely overlooked in clinical settings.

Our proposed research aims to determine the prevalence, dispersal, and contributions of small cryptic plasmids in the human gut microbiome during antimicrobial treatment by leveraging metagenomic data and advanced bioinformatic tools.

Furthermore, our comprehenive investigation will address the knowledge gap regarding how small cryptic plasmids contribute to the emergence and spread of multi-drug resistance in bacterial communities. Understanding these mechanisms could guide the development of innovative antimicrobial strategies.