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

Abstract

A clinically isolated pan-resistant <i>Klebsiella pneumoniae</i> strain (ST11), KPN142 was subjected to whole-genome sequencing. Genomic sequence of KPN142 showed that limited antibiotic resistances (β-lactams [<i>bla_shv-11</i>], sulfonamides [<i>sul1</i> and <i>dfrA22</i>], bacitracin [<i>bacA</i>], tetracycline [<i>tet34</i>], aminoglycosides [<i>ksgA</i>, <i>kdpE</i>, <i>aph(3)Ia</i>, <i>aac(3)III</i>, and <i>ant(3)Ia</i>], and chloramphenicol [<i>catA1</i>]) 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 <i>acrR</i> and <i>ramR</i> 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 <i>mgrb</i>, a suppressor in the expression of <i>phoPQ</i>, overexpression of which may confer the resistance of KPN142 to colistin B. In addition, <i>K. pneumoniae</i> KPN142 carries IS1, IS3, and <i>IntI1</i>, which means that KPN142 is able to transfer drug-resistance genes. Of note, we detected the overexpression of <i>acrB</i>, <i>ramA</i>, <i>phoP</i>, and <i>phoQ</i> by real-time quantitative reverse transcription-polymerase chain reaction, and carbonyl cyanide chlorophenylhydrazone was able to reverse the resistance patterns of <i>K. pneumoniae</i> 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 <i>phoPQ</i> mediates the resistance to colistin B in <i>K. pneumoniae</i> KPN142.