# Genomic survey uncovers the emergence of a multidrug-resistant dominant lineage in Proteus mirabilis populations

## TL;DR

A global genomic study reveals a multidrug-resistant Proteus mirabilis lineage that has spread widely and is linked to antibiotic resistance genes and adaptive traits.

## Contribution

Identification of a dominant multidrug-resistant P. mirabilis lineage with global spread and adaptive traits linked to agn43.

## Key findings

- Cluster-1 lineage carries high-prevalence carbapenemase genes blaKPC-2 and blaIMP-27.
- Cluster-1 diversified into China- and USA-associated subclades with distinct resistance genes.
- agn43 deletion reduces biofilm formation, heat tolerance, and swarming motility.

## Abstract

Proteus mirabilis, a Gram-negative bacterium renowned for its distinctive swarming motility, is a major causative agent of catheter-associated urinary tract infections (CAUTIs) and nosocomial complications. While advances in sequencing technologies have generated extensive genomic data, critical gaps persist in understanding the global population structure and evolutionary drivers of antimicrobial resistance in this pathogen. To address this knowledge gap, we performed a phylogenomic analysis of 1,142 P. mirabilis genomes spanning 34 countries and 16 ecological niches. Our investigation identified a dominant multidrug-resistant lineage (Cluster-1) carrying significantly elevated antimicrobial resistance gene burdens, including high-prevalence carbapenemase genes blaKPC-2 and blaIMP-27. Bayesian evolutionary dating traced the most recent common ancestor of Cluster-1 to approximately 1910, with subsequent expansion linked to acquisition of the autotransporter gene agn43 within the PmGRI1 genomic island. Notably, Cluster-1 diversified into two clinically significant subclades: a China-associated branch carrying blaKPC-2 and a USA-associated branch harboring blaIMP-27. Functional characterization revealed that agn43 deletion caused significant attenuation in biofilm formation, heat stress tolerance, and swarming motility. Our findings delineate the emergence of a globally disseminated P. mirabilis clone, highlighting the synergistic role of antimicrobial resistance and agn43-mediated adaptive traits in its epidemiological success.