The global prevalence, formation, and evolutionary inference of bacteria co-carrying the blaNDM and mcr resistance genes

Boqian Wang¹Kexin Li^2,3Mingliang Chen⁴Jingjing Fu^1,5Rui Zhang^1,2,3Liu Wanqiu^1,6Yuxin Wang^2,3Zhixi Peng^2,3Aimaiti Buaijier^1,3Xinru Zhao^1,3Hongbin Song²Hongguang Ren¹Xiaofeng Hu^2*

• ¹Academy of Military Medical Sciences, Beijing, China
• ²Center for Disease Control and Prevention of PLA, Beijing, China
• ³China Medical University, Shenyang, China
• ⁴Army Medical University, Chongqing, China
• ⁵Southern Medical University, Guangzhou, China
• ⁶University of South China School of Public Health, Hengyang, China

The global dissemination of bacteria harboring blaNDM and mcr genes, which confer co-resistance to carbapenem and polymyxin antibiotics, poses a catastrophic threat to public health due to the ineffectiveness of last-line antibiotics. This study integrated epidemiological and genetic analysis of 1,156 bacterial genomes from global databases and our de novo sequencing. We demonstrate that the current "human-animal-environment" transmission drives their rapid geographical expansion and dynamic succession of dominant bacterial lineages (predominantly Escherichia, Enterobacter, and Klebsiella) over time. Notably, we identified several pieces of evolutionary evidence to elucidate the genetic dynamics of co-resistant bacterial formation as well as related plasmids and chromosome fusion. Additionally, we find that both broad-host and narrow-host plasmids are closely associated with these phenomena, but possess distinct genetic functions. These findings elucidate the urgency of region-tailored surveillance, highlighting the need to target high-risk plasmid types and restrict nontherapeutic antibiotic use in agriculture to delay the "no-drug-available" crisis.