The MCR-1 colistin resistance: A new challenge to global public health

Abstract

Antibiotic resistance is becoming a global public health priority. The emergence of the notorious super-bugs that can produce the New Delhi β -lactamase 1 (NDM-1) had ever pushed us on the cusp of post-antibiotic era. The expression of NDM-1 (and its variants like NDM-5) allows the gut microbiota to gain the robust resistance to both extended spectrum β -lactamases (ESBL) and carbapenems, the two types of antibiotics extensively used for treatment of the multidrug- resistant bacteria. Colistin, referred to polymyxin E, belongs to a family of cationic polypeptide antibiotics, and acts as a final line of refuge against fatal infections by gram-negative pathogens with pan-drug resistance. Unfortunately, it seems likely that this last-resort antibiotics has been defied greatly by the appearance of colistin resistance. To the best of knowledge, three types of chemical modifications of the lipid A have been associated with the bacterial colistin resistance. Generally, the lipid A anchor of lipid polysaccharide (LPS) can be modified with amine-containing substitutes including (i) addition of phosphoethanolamine to 4′-phosphate position of sugar; (ii) modification of sugar with amino-arabinose at the 4′-phosphate position; and (iii) glycine (and/or diglycine) modification at 3′-linked secondary acyl chain. Consequently, the alteration of the LPS-lipid A moiety reduces the net negative charge of the bacterial outer-membrane, which in turn attenuates the binding of the cationic antimicrobial peptide colistin to bacterial surface. Thus, it is very true that divergent metabolic mechanisms are involved into bacterial colistin resistance. Very recently, a new mobilized colistin resistance gene ( mcr-1 ) is reported by a research group in China. The transferability of the MCR-1 by gene horizontal transfer enables a variety of bacteria to be tolerant with the antibiotic polymyxin, a last line of resort against multi-drug resistant enterobacteria. The global dissemination of the MCR-1 might pose a great challenge to the public health, implying the arrival of “post-antibiotics” era. It thus seems reasonable that the emergence of the MCR-1 colistin resistance attracted promptly extensive concerns worldwide. In this brief review, we concentrate on global epidemiology of the mcr-1 gene, diversified mcr-1 -bearing plasmids, complicated genetic content of the mcr-1 , and biochemical mechanism for the MCR-1. This review might allow us to better understand the MCR-1 colistin resistance, providing a clue to design strategies against the mcr-1 -harbouring super-bug.