Unknown

Dataset Information

0

The Klebsiella pneumoniae carbapenemase (KPC) β-Lactamase Has Evolved in Response to Ceftazidime Avibactam.


ABSTRACT: Klebsiella pneumoniae carbapenemase KPC is an important resistance gene that has disseminated globally in response to carbapenem use. It is now being implicated as a resistance determinant in Ceftazidime Avibactam (CAZ-AVI) resistance. Given that CAZ-AVI is a last-resort antibiotic, it is critical to understand how resistance to this drug is evolving. In particular, we were interested in determining the evolutionary response of KPC to CAZ-AVI consumption. Through phylogenetic reconstruction, we identified the variable sites under positive selection in the KPC gene that are correlated with Ceftazidime Avibactam (CAZ-AVI) resistance. Our approach was to use a phylogeny to identify multiple independent occurrences of mutations at variable sites and a literature review to correlate CAZ-AVI resistance with the mutations we identified. We found the following sites that are under positive selection: P104, W105, A120, R164, L169, A172, D179, V240, Y241, T243, Y264, and H274. The sites that correlate with CAZ-AVI resistance are R164, L169, A172, D179, V240, Y241, T243, and H274. Overall, we found that there is evidence of positive selection in KPC and that CAZ-AVI is the major selective pressure.

SUBMITTER: Garsevanyan S 

PROVIDER: S-EPMC10812414 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

The <i>Klebsiella pneumoniae</i> carbapenemase (KPC) β-Lactamase Has Evolved in Response to Ceftazidime Avibactam.

Garsevanyan Sona S   Barlow Miriam M  

Antibiotics (Basel, Switzerland) 20231231 1


<i>Klebsiella pneumoniae</i> carbapenemase KPC is an important resistance gene that has disseminated globally in response to carbapenem use. It is now being implicated as a resistance determinant in Ceftazidime Avibactam (CAZ-AVI) resistance. Given that CAZ-AVI is a last-resort antibiotic, it is critical to understand how resistance to this drug is evolving. In particular, we were interested in determining the evolutionary response of KPC to CAZ-AVI consumption. Through phylogenetic reconstructi  ...[more]

Similar Datasets

| S-EPMC10617341 | biostudies-literature
| S-EPMC5666153 | biostudies-literature
| S-EPMC10205629 | biostudies-literature
| S-EPMC10105652 | biostudies-literature
| S-EPMC11514958 | biostudies-literature
| S-EPMC9487638 | biostudies-literature
| S-EPMC10716778 | biostudies-literature
| S-EPMC8370223 | biostudies-literature
| S-EPMC8597731 | biostudies-literature
| S-EPMC10433922 | biostudies-literature