MgrB Alterations Mediate Colistin Resistance in Klebsiella pneumoniae Isolates from Iran

• Published in: Frontiers in microbiology Vol. 8; p. 2470
• Main Authors: Haeili, Mehri, Javani, Afsaneh, Moradi, Jale, Jafari, Zeinab, Feizabadi, Mohammad M, Babaei, Esmaeil
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18.12.2017
• Subjects: colistin resistance; Klebsiella pneumoniae; MgrB; Microbiology; PhoPQ; PmrAB; PhoPQ; colistin resistance; PmrAB; Klebsiella pneumoniae; MgrB
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2017.02470

Colistin is one of the last-resort therapeutic agents to combat multidrug-resistant Gram-negative bacteria (GNB) including . Although it happens rarely, resistance to colistin has been reported for several GNB. A total of 20 colistin resistant (col-R) and three colistin susceptible (col-S) clinical isolates of were studied to explore the underlying mechanisms of colistin resistance. The presence of plasmid encoded resistance genes, genes were examined by PCR. The nucleotide sequences of , and genes were determined. To evaluate the association between colistin resistance and upregulation of and operons, transcriptional level of the and genes encoding for lipopolysaccharide target modifying enzymes was quantified by RT-qPCR analysis. None of the plasmid encoded resistance genes were detected in the studied isolates. Inactivation of MgrB due to nonsense mutations and insertion of IS elements was observed in 15 col-R isolates (75%). IS elements (IS -like and IS -like families) most commonly targeted the coding region and in one case the promoter region of the Complementation with wild-type MgrB restored colistin susceptibility in isolates with altered . All col-R isolates lacked any genetic alterations in the , and genes and substitutions identified in the were not found to be involved in resistance conferring determined by complementation assay. Colistin resistance linked with upregulation of and operons with the and being overexpressed in 20 and 11 col-R isolates, respectively. Our results demonstrated that MgrB alterations are the major mechanisms contributing to colistin resistance in the tested isolates from Iran.