From the Research
Colistin resistance mechanisms primarily involve modifications to the bacterial outer membrane, specifically through the modification of lipopolysaccharide (LPS) or complete loss of LPS, which reduces the drug's ability to bind and disrupt cell integrity, as demonstrated in a recent study published in 2022 1. The most common mechanism is modification of LPS through addition of phosphoethanolamine or 4-amino-4-deoxy-L-arabinose to lipid A, which reduces the negative charge of the bacterial membrane and decreases colistin binding. This modification is often mediated by plasmid-borne mcr genes (particularly mcr-1 through mcr-10), which can transfer horizontally between bacteria, or by chromosomal mutations in the PmrA/PmrB and PhoP/PhoQ two-component regulatory systems, as discussed in a study published in 2021 2. Other resistance mechanisms include:
- Complete loss of LPS through mutations in lipid A biosynthesis genes
- Overexpression of efflux pumps that remove colistin from bacterial cells
- Formation of protective capsules or biofilms that prevent colistin from reaching its target These resistance mechanisms are particularly concerning because colistin serves as a last-resort antibiotic for multidrug-resistant Gram-negative infections, and the emergence of colistin resistance severely limits treatment options for these dangerous pathogens, as highlighted in studies published in 2021 3, 4. Furthermore, the use of colistin in combination with other antimicrobials can lead to the selection of pmrAB mutant strains, resulting in strains with modified LPS, as shown in a study published in 2022 1. It is essential to consider these resistance mechanisms when developing treatment strategies for infections caused by multidrug-resistant Gram-negative bacteria, and to prioritize the use of the most recent and highest quality evidence, such as the study published in 2022 1, to guide clinical decision-making.