Current Update on Intrinsic and Acquired Colistin Resistance Mechanisms in Bacteria

Abstract

Colistin regained global interest as a consequence of the rising prevalence of multidrug-resistant Gram-negative Enterobacteriaceae. In parallel, colistin-resistant bacteria emerged in response to the unregulated use of this antibiotic. However, some Gram-negative species are intrinsically resistant to colistin activity, such as Neisseria meningitides, Burkholderia species, and Proteus mirabilis. Most identified colistin resistance usually involves modulation of lipid A that decreases or removes early charge-based interaction with colistin through up-regulation of multistep capsular polysaccharide expression. The membrane modifications occur by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-l-arabinose on lipid A that results in decrease in the negative charge on the bacterial surface. Therefore, electrostatic interaction between polycationic colistin and lipopolysaccharide (LPS) is halted. It has been reported that these modifications on the bacterial surface occur due to overexpression of chromosomally mediated two-component system genes (PmrAB and PhoPQ) and mutation in lipid A biosynthesis genes that result in loss of the ability to produce lipid A and consequently LPS chain, thereafter recently identified variants of plasmid-borne genes (mcr-1 to mcr-10). It was hypothesized that mcr genes derived from intrinsically resistant environmental bacteria that carried chromosomal pmrC gene, a part of the pmrCAB operon, code three proteins viz. pEtN response regulator PmrA, sensor kinase protein PmrAB, and phosphotransferase PmrC. These plasmid-borne mcr genes become a serious concern as they assist in the dissemination of colistin resistance to other pathogenic bacteria. This review presents the progress of multiple strategies of colistin resistance mechanisms in bacteria, mainly focusing on surface changes of the outer membrane LPS structure and other resistance genetic determinants. New handier and versatile methods have been discussed for rapid detection of colistin resistance determinants and the latest approaches to revert colistin resistance that include the use of new drugs, drug combinations and inhibitors. Indeed, more investigations are required to identify the exact role of different colistin resistance determinants that will aid in developing new less toxic and potent drugs to treat bacterial infections. Therefore, colistin resistance should be considered a severe medical issue requiring multisectoral research with proper surveillance and suitable monitoring systems to report the dissemination rate of these resistant genes.

Evaluating the Prevalence and the Risk Factors of Gram-Negative Multi-Drug Resistant Bacteria in Eastern Saudi Arabia

“…may complicate the picture of antibiotics resistance especially when coupled with other resistance mechanisms such as reduced membrane permeability and active efflux pumps. 7 Since majority of the former resistant genes are carried on mobile elements like plasmids and conjugative transposons, this will ease the vertical transmission of resistance across other GNB occupying the same setting. Along with their increased antibiotic resistance profile, GNB are known to produce biofilms on biotic and abiotic surfaces such as catheters and medical equipment.…”

Effective Antimicrobial Solutions for Eradicating Multi-Resistant and β-Lactamase-Producing Nosocomial Gram-Negative Pathogens

“…Alarmingly, this isolate also exhibited resistance to the polymyxin class (and every other antibacterial agent tested), where the increasing use of colistin for the treatment of carbapenem-resistant bacterial infections is selecting for resistance. In addition, the unmonitored use of this agent in the agricultural sector is considered a major driver of resistance [ 18 ], with the WHO now listing colistin as a crucial last-resort agent. Carbapenem-resistant P. aeruginosa is at the top of the WHO priority list, along with carbapenem-resistant A. baumanii , and ESBL and carbapenemase-producing Enterobacteriaceae (primarily E. coli and K. pneumoniae ), where there is an urgent and unmet need for development of new antibiotics and infection-control strategies [ 19 ].…”

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

“…Their ability to bind the lipid A component of LPS makes them precious, the last resource weapons to fight septic shock, notwithstanding their known nephrotoxicity. Resistance has emerged, however, and is spreading at an alarming pace, putting the effectiveness of these valuable therapeutics at risk [ 170 , 171 ]. Last but not least, daptomycin.…”