Question

How is KPC resistance acquired? What genetic elements does it have and what resistance mechanisms do these confer?

Answer 1

KPC (Klebsiella pneumoniae Carbapenemase) or CRE (carbapenem-resistant Enterobacteriaceae) is one of the member of large family of bacteria i.e Enterobacteriaceae. Klebsiella causes infection in urinary tract and also cause pneumonia. In KPC, C denotes Carbapenemase (enzyme that are produced by the resistant KPC bacteria). KPC has ^blaKPC plasmid which confers resistance against various antibiotics.

The genetic elements of KPC are ^blaKPC plasmid and Transposon Tn440, both of which contains the gene for Carbapenemase (enzyme that are produced by the resistant KPC bacteria).

Different resistance mechanisms of KPC against Carbapenem antibiotic are :

• Efflux of carbapenem drug out of the bacterial cell by active transport.
• The lack of outer membrane proteins i.e OmpK35 and OmpK36 blocks the entry of carbapenem drug and hence develops carbapenem resistance.
• In KPC, C denotes Carbapenemase (enzyme that are produces by the resistant KPC bacteria), three categories of Carbapenemase enzyme are class A beta-lactamase, class B metallo-beta-lactamases and class D oxacillinase. All of them causes the hydrolysis of family of antibiotics called carbapenems. Carbapenems shares a common structure with penicilins and cephalosporin antibiotics.
• Finally, the production of AmpC cephalosporinases and ESBL (extended spectrum beta lactamases) causes the resistance against antibiotics.