Overexpression of Efflux Pumps Mediate Pan Resistance of <i>Klebsiella pneumoniae</i> Sequence Type 11

Abstract

A clinically isolated pan-resistant Klebsiella pneumoniae strain (ST11), KPN142 was subjected to whole-genome sequencing. Genomic sequence of KPN142 showed that limited antibiotic resistances (β-lactams [ bla shv-11 ], sulfonamides [ sul1 and dfrA22 ], bacitracin [ bacA ], tetracycline [ tet34 ], aminoglycosides [ ksgA , kdpE , aph(3)Ia , aac(3)III , and ant(3)Ia ], and chloramphenicol [ catA1 ]) were mediated by enzymes, and efflux pumps contributed most to pan resistance. Five types of multidrug resistance efflux pump families were identified, including the resistance nodulation division superfamily (AcrAB-TolC, AcrD, MdtABC, and KexD), the ATP-binding cascade superfamily (MacAB), the small multidrug resistance family (KpnEF), the multidrug and toxic compound extrusion family (KdeA), and the major facilitator superfamily (EmrAB). There was an AcrAB-TolC efflux pump system, and inhibitory regulatory gene acrR and ramR of system carried deletion mutation, which lead to overexpression of AcrAB-TolC efflux pump, and in turn plays key role in the pan resistance of KPN142. Moreover, we did not find mgrb , a suppressor in the expression of phoPQ , overexpression of which may confer the resistance of KPN142 to colistin B. In addition, K. pneumoniae KPN142 carries IS1, IS3, and IntI1 , which means that KPN142 is able to transfer drug-resistance genes. Of note, we detected the overexpression of acrB , ramA , phoP , and phoQ by real-time quantitative reverse transcription–polymerase chain reaction, and carbonyl cyanide chlorophenylhydrazone was able to reverse the resistance patterns of K. pneumoniae KPN142. In conclusion, we consider that the overexpression of AcrAB-TolC efflux pump mediates the resistance to most common clinical antimicrobial agents, and the overexpression of phoPQ mediates the resistance to colistin B in K. pneumoniae KPN142.

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