The Klebsiella pneumoniae carbapenemase (KPC) β-Lactamase Has Evolved in Response to Ceftazidime Avibactam
In: Antibiotics, Jg. 13 (2023-12-01), Heft 1, S. 40
Online
academicJournal
Zugriff:
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.
Titel: |
The Klebsiella pneumoniae carbapenemase (KPC) β-Lactamase Has Evolved in Response to Ceftazidime Avibactam
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Autor/in / Beteiligte Person: | Garsevanyan, Sona ; Barlow, Miriam |
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Zeitschrift: | Antibiotics, Jg. 13 (2023-12-01), Heft 1, S. 40 |
Veröffentlichung: | MDPI AG, 2023 |
Medientyp: | academicJournal |
ISSN: | 2079-6382 (print) |
DOI: | 10.3390/antibiotics13010040 |
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