Chromosomally encoded and plasmid-mediated polymyxins resistancein Acinetobacter baumannii: a huge public health threat

AbstractAcinetobacter baumannii is an opportunistic pathogen associated with nosocomial and community infections of great clinicalrelevance. Its ability to rapidly develop resistance to antimicrobials, especially carbapenems, has re-boosted the prescription anduse of polymyxins. However, the emergence of strains resistant to these antimicrobials is becoming a critical issue in severalregions of the world because very few of currently available antibiotics are effective in these cases. This review summarizes themost up-to-date knowledge about chromosomally encoded and plasmid-mediated polymyxins resistance in A. baumannii.Different mechanisms are employed by A. baumannii to overcome the antibacterial effects of polymyxins. Modification of theouter membrane through phosphoethanolamine addition, loss of lipopolysaccharide, symmetric rupture, metabolic changesaffecting osmoprotective amino acids, and overexpression of efflux pumps are involved in this process. Several genetic elementsmodulate these mechanisms, but only three of them have been described so far in A. baumannii clinical isolates such as mutationsin pmrCAB, lpxACD, and lpsB. Elucidation of genotypic profiles and resistance mechanisms are necessary for control and fightagainst resistance to polymyxins in A. baumannii, thereby protecting this class for future treatment.Keywords Outer membrane . Lipid A . Phosphoethanolamine transferase . Efflux pumps . Osmoprotective amino acids . mc