Within-host diversity of MRSA antimicrobial resistances (AMR). Within-host diversity of MRSA antimicrobial resistances (AMR)

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a risk factor for subsequent infection and the nose is the main reservoir for infecting isolates. Recent evidence suggests populations of MRSA colonizing isolates can vary genetically. The aim of this study was to measure the level of antimicrobial resistance (AMR) variability and potential mechanisms of horizontal gene transfer (HGT) in colonized patients. Methods: Nasal swabs from 38 MRSA carriers admitted to St Georges’ Hospital were plated and 20 individual colonies were each tested phenotypically for antibiotic susceptibility and genetically for lineage, carriage of 4 prophages and 3 plasmid families. Swabs were also tested for free bacteriophages and their capacity for transducing resistance genes. Results: Nine (24%) patients carried multiple phenotypic antibiogram variants, and 24 (63%) carried prophage and plasmid variants. If a single colony was selected for testing, the probability of detecting all phenotypic resistances in that patient was 87%. 64 different genetic profiles were detected, mostly in the MRSA CC22 background, with up to 8 variant but related profiles per patient. Nearly half of the patients carried detectable free bacteriophage, and phage successfully transduced resistance genes between laboratory and patient isolates in vitro. Whole genome sequencing (WGS) showed MRSA core genomes were relatively stable compared to resistances and mobile elements. Conclusion: Genetic variants of MRSA in nasal colonization populations are common and bacteriophage may play an important role in the HGT of AMR genes and other genetic elements. Accurate estimation of AMR and genetic variability has implications for diagnostics, epidemiology, antibiotic stewardship and selective pressures driving evolution of MRSA populations.