Global spread of carbapenem-resistant Providencia driven by high-risk lineages and plasmid co-evolution.

چکیده اصلی

Carbapenem-resistant Providencia (CRP) is a formidable opportunistic pathogen with extensive drug resistance, posing an increasing threat to human, animal, and environmental health. However, its global genomic epidemiology and resistome-plasmidome co-evolution within a One Health context remain poorly understood. Here, we conducted a comprehensive population genomic and plasmid analysis of 1197 CRP isolates from 35 countries spanning 2012-2025. We reclassified the CRP population into nine Providencia species, identifying P. stuartii and P. rettgeri as established epidemic species alongside the rapid emergence of P. hangzhouensis and P. huashanensis. We pinpointed 2019 as a critical inflection point, marking the transition from endemic stability to rapid global epidemic expansion (80.8% isolates in 2019-2025). Ten intercontinentally disseminated high-risk sequence types (e.g., ST46, ST79), each with strict species-ST specificity, were responsible for global spread. The bla NDM-1 gene (62.4% prevalence) was the predominant carbapenem gene, exhibiting strong geographic and species specificity and mutual exclusion with other major carbapenem genes. Plasmids encoded approximately 80% of antimicrobial resistance (AMR) genes, with 78.0% of these plasmids belonging to 75 stable clusters. These clusters evolved a dual specialist-generalist strategy, with the broad-host-range cluster 72 mediating interspecies AMR transmission and cluster 7 acting as a super-vector carrying six carbapenem genes. Importantly, CRP circulated across interconnected human, animal, and environmental reservoirs, with distinct host-associated species distributions suggesting ecological niche adaptation and potential cross-host dissemination of resistance determinants. These findings demonstrate that the global expansion of CRP is driven by the combined evolution of high-risk clones and mobile genetic elements across interconnected ecological sectors, underscoring the need for integrated One Health surveillance and coordinated interventions spanning clinical, veterinary, agricultural, and environmental settings.

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