Overexpression of Efflux Pumps Mediate Pan Resistance of Sequence Type 11.

A clinically isolated pan-resistant strain (ST11), KPN142 was subjected to whole-genome sequencing. Genomic sequence of KPN142 showed that limited antibiotic resistances (β-lactams [], sulfonamides [ and ], bacitracin [], tetracycline [], aminoglycosides [, , , , and ], and chloramphenicol []) 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 and 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 , a suppressor in the expression of , overexpression of which may confer the resistance of KPN142 to colistin B. In addition, KPN142 carries IS1, IS3, and , which means that KPN142 is able to transfer drug-resistance genes. Of note, we detected the overexpression of , , , and by real-time quantitative reverse transcription-polymerase chain reaction, and carbonyl cyanide chlorophenylhydrazone was able to reverse the resistance patterns of 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 mediates the resistance to colistin B in KPN142.