Research Progress in Colistin（COL）Resistance in Bacterial and Its Reversal Mechanism

doi:10.13560/j.cnki.biotech.bull.1985.2022-0384

Abstract

Abstract:

Colistin（COL）is presently considered the “last resort” of defense against human infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of COL,bacterial COL resistance is also increasing worldwide. It is extremely difficult to develop new antibacterial drugs with new targets,and combination drugs to reverse drug resistance are cost-effective strategies to combat MDR bacteria. Antibiotic adjuvants target non-essential functions of bacteria and enhance antibiotic activity,providing a cost-effective way to reverse bacterial resistance. Based on the summary of the action mechanism of COL and resistant mechanism in bacteria,this paper focuses on the reversal role of adjuvants on COL resistance in Gram-negative and its molecular mechanism are mainly discussed. More than 60 adjuvants that can reverse COL resistance have been reported to date. It has been proved that the disruption of the bacterial cell envelope,efflux pump inhibition are the expression decrease of mcr-1 gene or activity inhibition of MCR-1 protein the important mechanism of COL resistance reversal. The research status and existing problems on the reversal role of adjuvants on COL resistance and its molecular mechanism of adjuvants is analyzed,and its development trend is prospected. Screening of the efficient reversal adjuvants,dose-effect relationship of the reversal roles and in-depth mechanistic studies will be important development direction in the future.

Key words: colistin, resistance reversal, reversal mechanism, action mechanism, resistance mechanism

HU Gong-zheng, CUI Xiao-die, ZHAI Ya-jun, HE Dan-dan. Research Progress in Colistin（COL）Resistance in Bacterial and Its Reversal Mechanism[J]. Biotechnology Bulletin, 2022, 38(9): 28-34.

Figures/Tables 2

Fig. 1 General mechanism of Salmonella resistance to COL mediated by lipopolysaccharide（LPS）modification The TCS PhoQP activates the expressions of pmrD,PmrD activates PmrA,and PmrA activates cptA,pmr and arn operons. Both cptA and eptB modified the core region of LPS. The product arn replaces L-Ara4N,and the pEtN produced by mcr- gene and product pmr replaces the phosphate group in lipid A of LPS,the net charge of the OM has changed

Fig. 2 Molecular mechanism of reversing COL resistance in gram negative bacteria The reversal mechanisms related to the action mechanism of COL. a. damage the bacterial OM;b. enhances oxidative damage. The reversal mechanisms related to COL resistance mechanism;c. inhibition of mcr-1 expression;d. inhibition of MCR-1 protein;e. down regulation of TCS pmrAB expression;f. inhibition of multidrug efflux pump;g. inhibit the expression of OmpA protein;h. comprehensive reversal mechanism

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