From the Research
Chromosomal resistant genes, particularly MgrB, play a crucial role in antimicrobial resistance mechanisms, and their inactivation is a major mechanism of colistin resistance in Klebsiella pneumoniae and other Gram-negative bacteria, as shown in a recent study from 2024 1. The most recent and highest quality study, published in 2024, found that the disruption of the mgrB gene by the ISKpn26 insertion sequence is a primary colistin resistance mechanism in Klebsiella pneumoniae 1. When MgrB is inactivated, this leads to upregulation of the PhoP/PhoQ system, resulting in modification of lipopolysaccharide (LPS) through addition of phosphoethanolamine or 4-amino-4-deoxy-L-arabinose to lipid A, which reduces the negative charge of the bacterial outer membrane and decreases colistin binding. Other chromosomal resistance genes include pmrA/pmrB, phoP/phoQ, and crrAB two-component systems, which when mutated can also confer resistance to polymyxins. Additionally, chromosomal mutations in genes encoding drug targets (such as gyrA/parC for fluoroquinolones), drug uptake systems (porins like OmpK35/36), or efflux pump regulators can lead to resistance to various antibiotic classes. Some key points to consider when dealing with chromosomal resistant genes include:
- The role of MgrB in regulating the PhoP/PhoQ system and its impact on colistin resistance
- The importance of monitoring for colistin resistance in clinical isolates, as reported in a study from 2023 2
- The need for combination therapy, including high-dose carbapenems, aminoglycosides, tigecycline, or newer agents like ceftazidime-avibactam, depending on susceptibility testing results, as suggested by a study from 2022 3
- The emergence of mobilized colistin resistance (mcr) genes, which can spread by horizontal transfer and have chances of global dissemination, as discussed in a review from 2021 4
- The endemic nature of carbapenem and colistin resistance in certain regions, such as Greece, where a nationwide study from 2014 to 2017 found a high prevalence of colistin-resistant Klebsiella pneumoniae isolates with inactivated mgrB genes 5. Therefore, it is essential to prioritize the use of combination therapy and to monitor for colistin resistance in clinical isolates, as the emergence of chromosomal resistant genes, particularly MgrB, poses a significant threat to public health, as highlighted in the most recent study from 2024 1.