Genomic analysis of Proteus mirabilis: Unraveling global epidemiology and antimicrobial resistance dissemination − emerging challenges for public health and biosecurity
Shaqiu Zhang, Qianlong Li, Mingshu Wang, Renyong Jia, Shun Chen, Mafeng Liu, Dekang Zhu, Xinxin Zhao, Ying Wu, Qiao Yang, Juan Huang, Xumin Ou, Di Sun, Bin Tian, Yu He, Zhen Wu, Anchun Cheng
Abstract
• High antibiotic resistance in Chinese and livestock-derived P. mirabilis . • β-lactamase and carbapenemase genes widespread in P. mirabilis . • Significant clonal spread of P. mirabilis across countries and hosts. • ICEs, ISs, and plasmids are pivotal in spreading P. mirabilis resistance. • First global genomic analysis of P. mirabilis epidemic and resistance. Given the escalating public health threat posed by Proteus 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-quality P. mirabilis genomes 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. mirabilis isolates 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. mirabilis carries 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 of P. mirabilis ’s global resistance landscape, highlighting the need to designate it as a novel antimicrobial resistance indicator and implement long-term surveillance.