Acquired Resistance to Colistin via Chromosomal And Plasmid-Mediated Mechanisms in Klebsiella pneumoniae

The increasing prevalence of resistance to the last-resort antibiotics carbapenems is leading to increasing difficulties in treating infections caused by multidrug-resistant carbapenem-resistant Gram-negative bacteria such as Klebsiella pneumoniae . The situation has led to the reintroduction of a drug previously discontinued for use in humans - colistin. Colistin is a cationic polypeptide which binds to the negatively charged lipid A of the lipopolysaccharide on the outer membrane of Gram-negative bacteria, causing membrane destabilization, cell leakage and death. Although colistin can be used to successfully treat infections caused by carbapenem-resistant K. pneumoniae , colistin resistance is known to be inducible during colistin treatment and can be engendered via mutations and genetic alterations in chromosomal genes involved in the regulatory network controlling chemical modifications of the lipid A moiety on the lipopolysaccharide, reducing the negative charge of lipid A and its affinity for colistin. Furthermore, the recent discovery of plasmid-mediated colistin resistance via the mcr -genes, and the potential for plasmid-mediated resistance determinants to rapidly disseminate between strains, has given rise to concerns regarding the future usefulness of colistin as a last-resort antibiotic. This review describes the known colistin resistance mechanisms in K. pneumoniae and the epidemiology of plasmid-mediated colistin resistance determinants in association to the species.