Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain

Author:

Gong Yanqiao12,Feng Yu13,Lv Xiaoju14

Affiliation:

1. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China

2. Department of Infection Control, Minda Hospital, Hubei Minzu University, Enshi 445000, China

3. Center for Pathogen Research, West China Hospital, Sichuan University, Chengdu 610041, China

4. Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu 610041, China

Abstract

This study describes KPC-204, a novel variant of Klebsiella pneumoniae carbapenemase, characterized by a Lys-Asp-Asp (KDD) amino acid insertion at Ambler position 269 deviates from KPC-2. This variant was identified in an ST11-type clinical isolate of carbapenem-resistant Klebsiella pneumoniae from China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 was located on a highly mobile IncFII/IncR plasmid within a complex genetic structure that facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204’s contribution to increased resistance to ceftazidime-avibactam. The kinetic parameters showed that KPC-204 exhibited similar affinity to KPC-2 toward ceftazidime and reduced sensitivity to avibactam. Docking simulations revealed a weaker interaction between KPC-204 and avibactam compared to KPC-2. Mating experiments demonstrated the resistance’s transmissibility. This investigation underscores the evolving diversity of KPC variants affecting ceftazidime-avibactam resistance, highlighting the necessity for continuous monitoring.

Funder

Sichuan Provincial Health Commission

Publisher

MDPI AG

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