Molecular evaluation of colistin resistance in Klebsiella pneumoniae strains isolated from patients in hospitals of Qom province

چکیده مقاله

Background and Objectives: Colistin is considered as one of the last antibiotic choices for addressing infections resulting from multidrug-resistant Klebsiella pneumoniae. Nevertheless, the rising resistance to colistin is emerging as a growing threat to public health. The aim of the present study was to explore the molecular mechanisms underlying resistance to colis- tin in a clinical isolate of K. pneumoniae. Materials and Methods: Colistin resistance was confirmed through antimicrobial susceptibility testing, and the sequence type was identified using Multilocus sequence typing (MLST). The molecular mechanism of colistin resistance was inves- tigated by sequence analysis of resistance-associated loci, including mgrB, pmrAB, phoPQ, crrAB, and PCR detection of plasmid-mediated mcr genes. Results: Among the studied 38 clinical K. pneumoniae isolates, one strain was colistin-resistant, which belonged to sequence type ST377. PCR results showed that the colistin resistance genes carried by plasmid (mcr-1 to mcr-4) were not present. While gene sequencing revealed wild-type pmrAB and phoPQ, the mgrB and crrA genes were found to be disrupted by inser- tion of IS elements in the promoter (position-45) and coding regions (position +365/+366), respectively. Moreover, a Q296L amino acid substitution was detected in CrrB. Conclusion: This study demonstrates that resistance to colistin in the K. pneumoniae ST377 isolate was mainly mediated by inactivation of MgrB and CrrA without the involvement of mcr plasmid genes or pmrAB or phoPQ genetic alterations. To our knowledge, no previous study has reported insertion sequence-mediated disruption of the crrA coding region in K. pneumoniae. The results highlighted the complexity of chromosomal resistance mechanisms and the importance of molecu- lar surveillance in managing colistin-resistant infections.