Global Bibliometric and Phylogenetic Analysis of mcr-Mediated Colistin Resistance.

Abstract

The emergence and spread of mobilized colistin resistance (mcr) genes threaten the efficacy of colistin, a last-resort antibiotic used in the management of multidrug-resistant Gram-negative bacteria (GNB). This study was aimed at (1) providing a bibliometric assessment of the mcr-related research landscape and (2) conducting phylogenetic and metadata analyses of all known mcr gene variants to elucidate their relatedness and global distribution by country of origin, sample type, and harboring bacterial diversity. Bibliometric analysis was conducted following the SPAR-4-SLR methodology, where mcr-related publications were retrieved from Scopus and analyzed using diverse packages in R software, Datawrapper, the VOSviewer tool, and Biblioshiny. Genomic analysis was conducted on 116 complete mcr gene sequences retrieved from the National Center for Biotechnology Information (NCBI). A neighbor-joining phylogenetic tree was constructed to infer evolutionary relationships, and the associated metadata of sequences were analyzed. A total of 3936 mcr-related publications met the inclusion criteria. Since the discovery of mcr in 2015, research output has grown consistently through 2024, reflecting an intense global scientific mobilization and the rapid prioritization of colistin resistance given its significant public health threat. About 54.15% of studies appeared in Top Q1-Q2 journals, notably Frontiers in Microbiology and Antimicrobial Agents and Chemotherapy. The most cited work was Liu et al. (2016), with 4445 citations. China and India led in publications and collaborations, while China dominated funding. Phylogenetic analysis revealed 10 mcr variants, each clustering together. Distance analysis showed that Escherichia coli was the likely origin of mcr-1-2 and mcr-5 variants, Aeromonas of mcr-3, Moraxella of mcr-6, Klebsiella pneumoniae of mcr-7, Raoultella ornithinolytica of mcr-8, and Enterobacter cloacae of mcr-10. However, mcr-4 and mcr-9 showed multiple origins with similar branch lengths for E. coli, Salmonella, and Enterobacter. The widespread occurrence of mcr-1-10 across diverse bacterial species underscores the urgent need for an integrated, One Health surveillance approach to monitor and mitigate colistin resistance spread globally.