Molecular characteristics and genetic analysis of the genes related to carbapenemase, efflux pump, and outer membrane proteins in carbapenem-resistant Klebsiella pneumoniae.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a life-threatening pathogen that has not been fully investigated on a molecular basis. Therefore, the molecular mechanisms of carbapenem resistance in CRKP collected from medical institutions in Hyogo Prefecture has been analyzed. Antimicrobial susceptibilities and the presence of carbapenemase along with epidemiological analyzes using multilocus sequence typing (MLST) have been investigated. The relative expression of efflux pump genes and mutations of ompK35 and ompK36, encoding the outer membrane porin, were also assessed for their relationship with carbapenem resistance. Most of the collected 22 CRKP isolates were non-susceptible to imipenem (68.2%), meropenem (90.9%), and ertapenem (81.8%), but all 22 strains were susceptible to colistin. Twelve strains (54.5%) were detected for carbapenemase genes such as blaIMP-6. Sequence type 37 was detected by MLST in 10 strains (45.5%). Non-carbapenemase-producing strains had high resistance rates for three carbapenems, and the main cause of resistance was ompK35 mutation. In conclusion, the main cause of resistance was imipenemase metallo-β-lactamase (IMP-6) production in carbapenemase-producing strains, and ompK35 mutation in non-carbapenemase-producing strains. Susceptibility to carbapenem did not differ in CRKP regardless of carbapenemase production, except for imipenem susceptibility. This result contributes to a more insightful understanding of the mechanisms of CRKP in Japan.