Pathogen-Specific Architectures of Carbapenem Resistance: Hydrolysis, Transport and Target Engagement
- 1School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China
- 2School of Health, Guangdong Institute of Arts and Sciences, 78 Jiuzhoujiang Avenue, Zhanjiang 524400, China
Abstract
Although Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are all classified as carbapenem-resistant, they differ in how they control antibiotic access to its targets. This narrative review concerns resistant clinical isolates. It compares β-lactamases, drug uptake and efflux, and penicillin-binding proteins (PBPs), including their implications for β-lactam treatment. We use enzyme–transport–target architecture to describe functional relationships among these components in a specified organism and drug context. Evidence from the examined systems links protein homeostasis to enzyme stability, transport alterations to drug-specific responses, and treatment to changes in resistance determinants and bacterial population composition. For example, a PBP3 substitution increased the sulbactam–durlobactam MIC eightfold in an Acinetobacter baylyi model, whereas another substitution altered purified-protein reactivity without increasing the MIC. Clinical treatment evidence is assessed separately from these mechanistic findings. The review distinguishes pathogen-focused trials, observational outcomes and in vitro activity, and relates treatment options to carbapenemase class, susceptibility and infection site. It helps explain why shared resistance determinants can produce different susceptibility profiles by linking enzyme activity, drug access and target engagement to the response to specific β-lactams.
Related
- L-histidine metabolic reprogramming is associated with imipenem-relebactam resistance in carbapenem-resistant hypervirulent Klebsiella pneumoniae
- Association of Carbapenemase Gene Profiles with Ceftazidime–avibactam Resistance in Carbapenem-Resistant Klebsiella pneumoniae
- Wastewater is Not a Reliable Proxy for Clinical Carbapenem Resistance Prevalence in E. coli
- Carbapenem Resistance Among Gram-Negative Bacteria in Bioaerosols at Biomedical Waste Disposal Site in Ahmedabad, India
- Co-Circulation of ST11-KL30 and ST11-KL64 Carbapenem-Resistant Klebsiella pneumoniae in Urumqi, Xinjiang, China: Molecular Epidemiology, Antimicrobial Resistance, and Virulence
BibTeX
@article{xiang2026pathogenspecific,
title = {{Pathogen-Specific Architectures of Carbapenem Resistance: Hydrolysis, Transport and Target Engagement}},
author = {Yitao Xiang and Weisheng Chen and Yina Xuan and Guangying Chen and Li Yu and Xiaochan Liu and Yujie Cai and Fangzhen Luo},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111568},
url = {https://www.mdpi.com/2218-273X/16/11/1568},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pathogen-Specific Architectures of Carbapenem Resistance: Hydrolysis, Transport and Target Engagement
AU - Yitao Xiang
AU - Weisheng Chen
AU - Yina Xuan
AU - Guangying Chen
AU - Li Yu
AU - Xiaochan Liu
AU - Yujie Cai
AU - Fangzhen Luo
PY - 2026
DA - 2026/10/27
JO - Biomolecules
DO - 10.3390/biom16111568
UR - https://www.mdpi.com/2218-273X/16/11/1568
AB - Although Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are all classified as carbapenem-resistant, they differ in how they control antibiotic access to its targets. This narrative review concerns resistant clinical isolates. It compares β-lactamases, drug uptake and efflux, and penicillin-binding proteins (PBPs), including their implications for β-lactam treatment. We use enzyme–transport–target architecture to describe functional relationships among these components in a specified organism and drug context. Evidence from the examined systems links protein homeostasis to enzyme stability, transport alterations to drug-specific responses, and treatment to changes in resistance determinants and bacterial population composition. For example, a PBP3 substitution increased the sulbactam–durlobactam MIC eightfold in an Acinetobacter baylyi model, whereas another substitution altered purified-protein reactivity without increasing the MIC. Clinical treatment evidence is assessed separately from these mechanistic findings. The review distinguishes pathogen-focused trials, observational outcomes and in vitro activity, and relates treatment options to carbapenemase class, susceptibility and infection site. It helps explain why shared resistance determinants can produce different susceptibility profiles by linking enzyme activity, drug access and target engagement to the response to specific β-lactams.
SN - 2218-273X
ER -