The colistin resistance pandemic: A dual threat from plasmid-encoded mobilised colistin resistance genes and chromosomal mutations.

Abstract

Background: Colistin remains a critical last-line therapeutic option against multidrug-resistant Gram-negative infections; but its utility is threatened increasingly by the global spread resistance determinants. Resistance emerges through two principal genetic pathways: horizontal transmission of mcr genes enabling rapid interspecies dissemination, and vertical chromosomal mutations facilitating clonal expansion.

Aim: To compare plasmid-mediated and chromosomal colistin resistance mechanisms and examine their clinical significance, epidemiological implications, diagnostic challenges, and surveillance barriers within a One Health framework.

Methods: For this narrative, non-systematic review, searches were conducted in PubMed, MEDLINE, Web of Science, Scopus and African Journals Online (AJOL) to identify studies on colistin resistance, its emergence, clinical implications, and related surveillance and diagnostic barriers.

Results: Several genetic determinants influence colistin susceptibility; notably, mcr variants and chromosomal mutations in Lipid A modification genes (e.g., pmrA, pmrB and mgrB) reduce colistin binding and bactericidal activity. In African and other resource-limited settings, limited laboratory infrastructure further complicates detection and surveillance, underscoring the need for context-appropriate diagnostics and antimicrobial stewardship. Collectively, these factors pose major clinical and epidemiological concerns.

Conclusion: Although surveillance-driven stewardship may mitigate resistance trends, its effectiveness is constrained by the convergence of colistin and carbapenem resistance, increasing the risk of pan-drug-resistant infections. Rapid field-deployable diagnostics and harmonised global surveillance systems that consider the distinct evolutionary trajectories of plasmid-mediated and chromosomal resistance remain urgently needed.

What this study adds: This review highlights the contrasting evolutionary pathways of plasmid-mediated and chromosomal colistin resistance and emphasises the importance of integrated surveillance, diagnostics, and stewardship strategies within a One Health approach.