The Role of IncC Plasmids in Antimicrobial Resistance: Implications from the Genomic Study of Providencia stuartii

NDM-1 producing Providencia stuartii isolates were identified carrying plasmid-driven carbapenemase determinants that sharply narrow therapeutic options in hospitalized patients.

Whole-genome sequencing with long-read confirmation showed that all four closely related isolates carried ~150 kb, conjugative IncC plasmids that harbored a multidrug resistance cassette including blaNDM-1, blaCTX-M-3, blaCMY-6, rmtC and multiple aminoglycoside and sulfonamide determinants. Hybrid assemblies resolved complete chromosomes and plasmids and documented nearly 100% sequence identity across the IncC backbones.

Pairwise core-genome distances between isolates were minimal (1–6 SNPs), and the four cases were recovered from a single ICU over six weeks, consistent with a small hospital cluster. The combination of a conserved plasmid backbone and tight chromosomal relatedness refines plasmid epidemiology by demonstrating a stable, transferable backbone recurring across temporally proximate cases.

IncC plasmids encode conjugative type IV secretion systems and retain tra operon elements that support intercellular transfer; the recovered plasmids showed high sequence identity and limited structural variation, consistent with preserved transfer capacity. Notably, the IncC backbones carried a broad resistome (15 resistance genes) together with small Col-type plasmids bearing qnrD variants, indicating a multi-plasmid architecture that elevates cumulative resistance. Conserved conjugative function combined with a broad resistance payload facilitates efficient cross-species movement of carbapenemase genes, reducing available treatment options and increasing outbreak potential among Gram-negative pathogens.

Surveillance that integrates chromosomal and plasmid analyses detects both clonal expansion and horizontal plasmid movement, enabling clear discrimination between strain transmission and plasmid dissemination within and between wards. Combining population-scale short-read surveillance for rapid screening with targeted long-read or hybrid assemblies for complete plasmid resolution and plasmid typing improves tracing of transmission chains, informs prioritization of control measures, and enhances allocation of infection-prevention resources.