Developing a novel approach to complex evolution of antimicrobial resistance via mobile genetic elements from a persistent environmental biofilm

Author:

Mathers Amy1ORCID,Li Thomas1,He Qijun1,Narendra Sharvari1,Stoesser Nicole2ORCID,Eyre David2ORCID,Walker Sarah2,Barry Katie1,Castañeda-Barba Salvador1ORCID,Huang Fenix Wenda1,Parikh Hardik3,Kotay Shireen1,Crook Derrick2,Reidys Christian4

Affiliation:

1. University of Virginia

2. University of Oxford

3. Univeristy of Virginia

4. Uiversity of Virginia

Abstract

Abstract

Mobile genetic elements are key to the global emergence of antibiotic resistance. We successfully reconstructed the complete bacterial genome and plasmid assemblies of isolates sharing the same blaKPC carbapenemase gene to understand evolution over time in six confined hospital drain biofilms over five years. From 82 isolates we identified 14 unique strains from 10 species with 113 blaKPC−carrying plasmids across 16 distinct replicon types. To assess dynamic gene movement, we introduced the 'Composite-Sample Complex', a novel mathematical approach to using probability to capture the directional movement of antimicrobial resistance genes accounting for the co-occurrence of both plasmids and chromosomes within an isolate, and highlighting likely donors and recipients. From the validated model, we demonstrate frequent transposition events of blaKPC from plasmids to other plasmids, as well as integration into the bacterial chromosome within specific drain biofilms. We present a novel approach to estimate the directional movement of antimicrobial resistance via gene mobilization.

Publisher

Springer Science and Business Media LLC

Reference63 articles.

1. CDC. Antibiotic Resistance Threats in the United States. (Centers for Disease Control and Prevention, Atlanta, GA, 2019).

2. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis;Antimicrobial Resistance Collaborators;Lancet,2022

3. Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC;Sheppard AE;Antimicrob Agents Chemother,2016

4. The A to Z of A/C plasmids;Harmer CJ;Plasmid,2015

5. The Hospital Water Environment as a Reservoir for Carbapenem-Resistant Organisms Causing Hospital-Acquired Infections-A Systematic Review of the Literature;Gordon A;Clinical Infectious Diseases,2017

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