Genotypic, phenotypic, and in silico analysis of carbapenem-resistant Klebsiella pneumoniae

Abstract

Due to an increase in serious infections and a lack of efficient therapies, Klebsiella pneumoniae has recently gained more recognition. The production of carbapenemases is one of the most common strategies by which K. pneumoniae acquire resistance to carbapenems which is considered the last resort of antibiotics. Previously collected isolates from different clinical settings and on the basis of their genetic profile, mainly the absence and presence of single or dual carbapenemases (OXA-181, OXA-232, NDM-1, NDM-5, NDM-5+OXA-181, and NDM-1+OXA-232), mutations in porins, and efflux pumps, seven isolates (M40, M52, M39, J20, M53, M49, and M17B) were selected. Its phenotypic resistance against two carbapenem drugs (ertapenem and meropenem) was checked and we found NDM-5 followed by OXA-181 and NDM-5+OXA-181 carrying isolates showed high MIC values. Further, no significant differences were observed either in the presence of efflux pumps or mutations in porins among isolates. By molecular docking, among single amino acid differences between OXA-181 and OXA-232 and with two amino acids differences between NDM-1 and NDM-5, OXA-232 and NDM-5 showed a higher binding affinity than OXA-181 and NDM-1 with both antibiotics. It is concluded that the presence of specific carbapenemases or combinations of the same can drastically increase MIC values. The presence of NDM-5, and OXA-181, or their combinations is more fatal than NDM-1+OXA-232.