Genomic analysis of Proteus mirabilis: Unraveling global epidemiology and antimicrobial resistance dissemination − emerging Challenges for public health and Biosecurity

Given the escalating public health threat posed byProteus mirabilis(P. mirabilis) and its rapidly evolving drug resistance, it is imperative to elucidate its global epidemiology and resistance mechanisms through a comprehensive genomic lens. As of August 2024, 3,403 high-qualityP. mirabilisgenomes were retrieved from public databases (total 3,752), spanning 58 countries/regions, with the United States showing the highest report rate (52.51 %). Human-derived isolates, particularly from urine (34.47 %), were the primary source. A total of 239 antibiotic resistance genes (ARGs) were identified in P. mirabilis, with β-lactamase and carbapenemase genes being particularly widespread and isolates from China harboring the highest ARG counts. Globally,P. mirabilisisolates were categorized into 17 distinct clusters, with U.S. isolates showing the widest phylogenetic spread. Minimal SNP variations among isolates from different countries and hosts suggest transnational and cross-host clonal propagation. Frequent clonal transmission was also observed among diverse hosts and clinical sources.P. mirabiliscarries numerous integrative and conjugative elements (ICEs), some facilitating ARG dissemination (n = 215). Prophages, though ubiquitous, contributed minimally to ARG spread. Spearman's analysis revealed significant correlations between ARGs and insertion sequences (ISs), replicons, and ICEs. Ancestral state analysis indicated prophages were mainly acquired horizontally, while other mobile genetic elements (MGEs) were largely clonally transmitted. This study provides the first comprehensive genomic analysis ofP. mirabilis's global resistance landscape, highlighting the need to designate it as a novel antimicrobial resistance indicator and implement long-term surveillance.