Proteus mirabilis entails a switch from commensal to pathogen - Genomic insights from a blaTEM-1B-harboring novel isolate from India.

Abstract

BackgroundProteus mirabilis is an opportunistic pathogen that can shift from gut commensalism to causing severe urinary tract and bloodstream infections. The genomic basis of P. mirabilis transition from commensalism to severe infection is not well understood, especially in Indian clinical isolates. This study aimed to explore the genomic attributes of a prevalent P. mirabilis strain in India. MethodsWhole-genome sequencing (WGS) was performed on a clinical P. mirabilis isolate by using NGS. AMR genes and virulence factors were identified using ResFinder/CARD and VFDB, respectively. Sequence typing was performed with MLST. Protein-protein interactions and noncoding RNAs were analyzed using STRING, CytoHubba, and BAKTA. ResultsWGS confirmed the multidrug-resistant nature of the isolate, revealing a broad repertoire of AMR genes, including blaTEM-1B, conferring resistance to beta-lactam antibiotics. Several resistance determinants were co-localised with insertion sequences on a single contig, indicating a high potential for horizontal gene transfer. The virulome profile highlighted multiple fimbrial genes, hemolysins, and toxin-encoding loci, together supporting strong adhesion, biofilm formation, and host tissue damage. Comparative analysis revealed unique genomic signatures not present in reference isolates, including additional virulence determinants and mobile genetic elements. MLST profile of the isolate is closely related to ST-675 & ST-797, while virulence typing (vST-1157) indicated a novel profile distinct from reference ST-675 strains. Insilico protein-protein interaction of this isolate revealed a highly interconnected virulence network, with urease, fimbrial adhesins, and hemolysins emerging as central functional modules driving pathogenicity. In addition, a noncoding RNA was identified within the genomic context of the ure operon (Contig 10), suggesting a possible regulatory role in urease expression. PPI network analysis highlighted urease, fimbrial proteins, and hemolysins as central hubs contributing to pathogenicity. ConclusionsThis study presents the first genomic characterization of a multidrug-resistant P. mirabilis clinical isolate from India, designated as P. mirabilis strain Indica. The convergence of AMR genes, virulence factors, MGEs and a novel noncoding RNAs linked to urease expression highlights the emergence of a high-risk variant in India. These findings have significant implications for infection control and emphasize the need for genomic surveillance to guide therapeutic strategies and develop new interventions globally.