Draft genome sequencing of Proteus mirabilis strain Indica (ST286) reveals antimicrobial resistance and virulence...

Proteus mirabilis is a Gram-negative, motile bacterium that typically colonizes the human gastrointestinal tract as a commensal organism. Under favorable conditions, particularly in hospitalized or immunocompromised individuals, as an opportunistic pathogen, causing a range of infections including catheter-associated urinary tract infections, wound infections and bacteremia. Its pathogenic potential is linked to a combination of virulence traits such as urease production, swarming motility, biofilm formation and the ability to acquire antimicrobial resistance determinants, which together facilitate persistence, tissue invasion and treatment failure. In this study we aim to understand the genomic attributes of a P. mirabilis clinical isolate from India.

The bacterial isolate was recovered from a clinical sample, followed by antimicrobial susceptibility testing (AST) using standard methods. Whole-genome sequencing was performed on the Illumina platform. De novo genome assembly and annotation were conducted, followed by multilocus sequence typing (MLST), virulence sequence typing and analysis of the resistome, virulome and mobile genetic elements using established bioinformatics pipelines. In silico protein-protein interaction (PPI) network analysis was performed to identify key functional hubs associated with pathogenicity.

WGS confirmed the multidrug-resistant (MDR) phenotype of the isolate, revealing a diverse array of antimicrobial resistance genes, including blaTEM-1B. The virulome analysis identified multiple fimbrial adhesins, hemolysins and toxin-encoding genes, collectively supporting adhesion, biofilm formation and host tissue damage. Multilocus sequence typing assigned the isolate to a previously unreported sequence type, designated ST286 in the PubMLST database., Virulence sequence typing indicated the profile as vST-1157 by the PubMLST database. Protein-protein interaction network analysis identified the hemolysin genes hpmA and hpmB, along with the fimbrial operon regulator mrpA, as major hub nodes with extensive connectivity. These hubs were strongly linked to multiple interaction partners, indicating their central role in mediating host-pathogen interactions, inflammation and tissue damage.

This study provides a comprehensive genomic insight into a novel multidrug-resistant P. mirabilis strain Indica, with a unique MLST profile isolated from India. The study also reveals the presence of antimicrobial resistance and virulence associated genes. The identification of hemolysin and fimbriae-associated hub genes as central nodes within the interaction network underscores their pivotal role in driving P. mirabilis virulence and host pathogen interaction. Also underscores the importance of genomic surveillance in geographically under represented areas. These findings provide a network-level perspective on P. mirabilis pathogenic mechanisms and highlight key virulence hubs as potential targets for therapeutic intervention.