Colistin Resistance in Acinetobacter baumannii: Molecular Mechanisms and Epidemiology

Acinetobacter baumannii is recognized as a clinically significant pathogen causing a wide spectrum of nosocomial infections. Colistin was considered a last-resort antibiotic for the treatment of infections caused by multidrug-resistant A. baumannii. Since the reintroduction of colistin, a number of mechanisms of colistin resistance in A. baumannii have been reported, including complete loss of LPS by inactivation of the biosynthetic pathway, modifications of target LPS driven by the addition of phosphoethanolamine (PEtN) moieties to lipid A mediated by the chromosomal pmrCAB operon and eptA gene-encoded enzymes or plasmid-encoded mcr genes and efflux of colistin from the cell. In addition to resistance to colistin, widespread heteroresistance is another feature of A. baumannii that leads to colistin treatment failure. This review aims to present a critical assessment of relevant published (>50 experimental papers) up-to-date knowledge on the molecular mechanisms of colistin resistance in A. baumannii with a detailed review of implicated mutations and the global distribution of colistin-resistant strains.

Automated summary

A. baumannii is a clinically significant pathogen causing various nosocomial infections. Colistin, as a last-resort antibiotic, is used to treat multidrug-resistant A. baumannii infections. However, several mechanisms of colistin resistance in A. baumannii have been reported, including loss of LPS, modifications of target LPS, and efflux of colistin. In addition, widespread heteroresistance in A. baumannii contributes to colistin treatment failure. This review critically assesses the molecular mechanisms and global distribution of colistin-resistant strains in A. baumannii based on more than 50 experimental papers.