Evidence map›Paper›PMID 41946819›Full record

ArticleCommunications biology2026

Reduced catalytic activity of KPC β-lactamase can increase ceftazidime resistance.

André Birgy, Dignite Fabrice Ngango, Murugesan Palaniappan, Shahlo O Solieva, Devin G Kelly, Zhizeng Sun, Gregory Bowman, Timothy Palzkill

Abstract read
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In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

André BirgyVerna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9462-0582
Dignite Fabrice NgangoVerna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0009-0001-3455-3338
Murugesan PalaniappanCenter for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Shahlo O SolievaDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5350-2184
Devin G KellyDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9063-4899
Zhizeng SunVerna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA.
Gregory BowmanDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2083-4892
Timothy PalzkillVerna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA. timothyp@bcm.edu.ORCID http://orcid.org/0000-0002-5267-0001

Funding

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI32956
6 · The paper itself

Abstract

β-Lactamases confer bacterial resistance by hydrolyzing β-lactam antibiotics. Klebsiella pneumoniae carbapenemases (KPCs) are a major cause of resistance to carbapenems, but combinations of β-lactams with β-lactamase inhibitors, such as ceftazidime/avibactam, initially restored activity against these enzymes. However, treatment has driven the emergence of KPC variants that evade inhibition. Here we investigate the evolutionary and mechanistic consequences of three clinically observed substitutions -D179Y, T243M and H274Y- that together convert the broad-spectrum KPC-2 enzyme into a variant specialized for ceftazidime/avibactam resistance. Using steady-state and pre-steady-state kinetic analyses with ceftazidime, cephalothin and imipenem, we show that T243M enhances cephalosporin hydrolysis, whereas H274Y modulates this effect. Introduction of D179Y decreases both k

Indexed as

Anti-Bacterial AgentsBacterial Proteinsbeta-LactamasesCeftazidimeKlebsiella pneumoniaeAzabicyclo CompoundsDrug CombinationsKineticsMicrobial Sensitivity TestsMutationThird Generation CephalosporinsAnti-Bacterial Agentsavibactam, ceftazidime drug combinationAzabicyclo CompoundsBacterial Proteinsbeta-LactamasesCeftazidimeDrug CombinationsThird Generation Cephalosporins

Identifiers

PMID41946819
PMCPMC13233964

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.