Background: Colistin is regarded as the final option for treating Gram-negative bacteria that are resistant to several drugs. A common resistance mechanism for colistin in Klebsiella pneumoniae is mgrB gene inactivation. Inactivation of mgrB activates the PhoPQ which upregulates the PmrAB leading to resistance by lipopolysaccharide modification. Colistin resistance has been reported in Klebsiella pneumoniae, still, studies related to molecular mechanisms of this resistance are lacking.
Aim: Role of mgrB in colistin resistance
Methods: In this study, eight colistin-resistant clinical Klebsiella pneumoniae were selected, and performed broth microdilution followed by Rapid polymyxin NP test for screening of colistin resistance. PCR was performed for different types of mcr genes. MgrB was amplified and sequenced. Quantitative real-time PCR was performed for mgrB, PmrA, PmrB, PhoP, and PhoQ genes. Further, clonal analysis by ERIC PCR was done.
Results: Colistin MIC of 4μg/ml has been shown by the isolates. No mcr gene was detected. Positive amplification for the mgrB gene was found in all the isolates. Sequence analysis of the mgrB gene found no mutation however, higher expression in the mgrB, PmrA, PmrB, PhoP, and PhoQ genes of all the eight colistin-resistant isolates could be observed when the isolates were exposed to colistin and Mg2+ pressure. Clonal analysis exhibited seven different haplotypes of Klebsiella pneumoniae.
Conclusion: This study provides firsthand knowledge about molecular mechanisms of colistin resistance in Klebsiella pneumoniae in this geographical area. Enhancement in mgrB expression in the presence of colistin and Mg2+ pressure regardless of any mutation has a remarkable impact in the context of colistin resistance mechanisms in clinical Klebsiella pneumoniae.
Key words: Colistin resistance, Klebsiella pneumoniae, mgrB, PhoPQ, PmrAB
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