Colistin Resistance in Acinetobacter baumannii: Molecular Mechanisms and Epidemiology

Abstract

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.

Characterization of antibiotic and disinfectant susceptibility in biofilm-forming Acinetobacter baumannii: A focus on environmental isolates

“…In contrast, in the case of clinical isolates, carbapenem-resistance had a lower, while aminoglycoside-resistance had a higher prevalence, respectively [ 24 ]. Nonetheless, colistin had largely retained its effectiveness in both isolate groups, which corresponds to other reports in the literature [ 47 ]. Phenotypic expression of efflux pumps was substantially higher in environmental isolates (48.25% vs. 27.51%), while MDR rates were similar (49.12% vs. 42.72%), although this could have been influenced by the difference in the number of isolates involved in the two studies [ 24 ].…”

Multiple heteroresistance to tigecycline and colistin in Acinetobacter baumannii isolates and its implications for combined antibiotic treatment

“…One amino acid was found in receiver domain of PmrA in FA1318-COL-RP. Amino acid substitutions in HisKA and HAMP domains of PmrB and receiver domain of PmrA have been reported to be responsible for increase of colistin MIC associated in A. baumannii [ 17 – 19 ]. Different amino acid alterations in the seven colistin-resistant subpopulations suggest that each developed independently.…”

Changes in Antibiotic Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Clinical Isolates in a Multi-Profile Hospital in Years 2017–2022 in Wroclaw, Poland

“…The first is that there is a mutation causing a complete absence of LPS and, consequently, of lipid A, which is the target site for colistin. The second, on the other hand, suggests that lipid A is present, but in a form altered by mutation of the pmrA and/or pmrB gene, which affects the lowering of colistin's affinity for LPS [47]. Increasingly, clinicians are also encountering multidrug-resistant strains, which is probably due to prior antibiotic therapy, very often inappropriately administered [48].…”