Polymyxins resistance : an overview of molecular mechanisms and genetic determinants

Abstract

Emergence of antimicrobial resistant bacteria is a majorworldwide public health issue. During the past decades, the misuse/overuse of antibiotics accelerated the development and dissemination of antimicrobial resistance, especially in multidrug-resistant Gram-negative bacilli (MDR-GN). Under this scenario, old drugs have been reconsidered. Since most available therapeutical options may fail in the treatment of some infections caused by MDR-GN, the polymyxins have arisen at the frontline of combating these highly resistant bacteria. As a consequence, resistance to polymyxins is growing in different geographical regions, compromising even more the treatment of infections caused by MDR-GN. These bacteria employ several strategies to protect themselves against polymyxins, such as mechanisms associated with changes in chromosomal genes, including lipopolysaccharide (LPS) modifications, overproduction of capsules, expression of efflux systems and enzymatic antibiotic inactivation. Worryingly, mechanisms related to plasmid-located genes have also been identified: the mobile colistin resistance gene (mcr), which threatens to increase the dissemination of resistance to polymyxins. The knowledge about mechanisms behind polymyxins resistance are useful to understand the epidemiology of this phenotype and to control the dissemination. For this purpose, this review aimed to discuss and update the main mechanisms involved in resistance to polymyxins.