The following is a summary of the “A novel KPC-113 variant conferring carbapenem and ceftazidime-avibactam resistance in a multidrug-resistant Pseudomonas aeruginosa isolate,” published in the March 2023 issue of Clinical Microbiology and infections Disease by Yang, et al.

Their goal in conducting this research was to understand better the unique KPC-113 variant found in clinical Pseudomonas aeruginosa isolate R20-14. R20-14 had Illumina and Oxford Nanopore sequencing performed on its genomic DNA. Conjugation experiments were performed to gauge the efficiency of plasmid horizontal transfer. The MICs of various bacterial strains were determined via broth microdilution techniques. Various carbapenemase detection methods were evaluated for their ability to detect KPC-113. Using a spectrophotometer, they compared KPC-113’s kinetic parameters to those of KPC-2. Schrödinger was used to model the structure of KPC-2 and KPC-113 and to carry out molecular docking.

The multidrug-resistant strain R20-14, sequence type 3903, was resistant to carbapenems and ceftazidime-avibactam (CZA). Genomic sequencing and S1-nuclease pulsed-field gel electrophoresis identified plasmid pR20-14 carrying bla_KPC-113, which showed a high conjugation frequency and was similar to previously reported type I KPC-encoding P. aeruginosa plasmids. To make DH5 and PAO1 transformants resistant to carbapenem and CZA, the KPC-113 strain inserted a glycine residue between Ambler positions 266 and 267 in KPC-2. Observations from diagnostic tests indicated that KPC-113 functioned in a fashion analogous to that of KPC-2. 

Compared to KPC-2, KPC-113 showed decreased catalytic ability to carbapenems and ceftazidime and poor response to avibactam inhibition. KPC-113’s binding mode differed from KPC-2’s due, at least in part, to a flatter binding pocket, as predicted by the structural models. KPC-113 is a new variant of KPC that mediates resistance to carbapenems and carbapenem-like drugs. The fact that bla_KPC-113 can efficiently horizontally transfer and render both carbapenems and CZA ineffective is extremely problematic. Great measures must be taken to halt its spread in medical facilities.

Source: sciencedirect.com/science/article/abs/pii/S1198743X22005274