Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii

Abstract Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occ...

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Main Authors: Bogdan M. Benin, Trae Hillyer, Noah Aguirre, Yuk Yin Sham, Belinda Willard, Woo Shik Shin
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-81501-z
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author Bogdan M. Benin
Trae Hillyer
Noah Aguirre
Yuk Yin Sham
Belinda Willard
Woo Shik Shin
author_facet Bogdan M. Benin
Trae Hillyer
Noah Aguirre
Yuk Yin Sham
Belinda Willard
Woo Shik Shin
author_sort Bogdan M. Benin
collection DOAJ
description Abstract Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occur. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be have some predictability based on structural factors. Additionally, the identified minor isoforms also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe therefore somewhat predictable based on specific structural properties and further investigation may lead to new strategies for mitigating antibiotic resistance.
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institution Kabale University
issn 2045-2322
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publishDate 2024-12-01
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series Scientific Reports
spelling doaj-art-29fa4c864f8745a2bd61fbd8a43aabb32024-12-29T12:16:44ZengNature PortfolioScientific Reports2045-23222024-12-011411910.1038/s41598-024-81501-zCarbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumanniiBogdan M. Benin0Trae Hillyer1Noah Aguirre2Yuk Yin Sham3Belinda Willard4Woo Shik Shin5Department of Pharmaceutical Sciences, Northeast Ohio Medical UniversityDepartment of Pharmaceutical Sciences, Northeast Ohio Medical UniversityDepartment of Pharmaceutical Sciences, Northeast Ohio Medical UniversityDepartment of Integrative Biology and Physiology, University of MinnesotaProteomics and Metabolomics Core, Lerner Research Institute, Cleveland ClinicDepartment of Pharmaceutical Sciences, Northeast Ohio Medical UniversityAbstract Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occur. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be have some predictability based on structural factors. Additionally, the identified minor isoforms also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe therefore somewhat predictable based on specific structural properties and further investigation may lead to new strategies for mitigating antibiotic resistance.https://doi.org/10.1038/s41598-024-81501-z
spellingShingle Bogdan M. Benin
Trae Hillyer
Noah Aguirre
Yuk Yin Sham
Belinda Willard
Woo Shik Shin
Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii
Scientific Reports
title Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii
title_full Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii
title_fullStr Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii
title_full_unstemmed Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii
title_short Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii
title_sort carbapenem induced β lactamase isoform expression trends in acinetobacter baumannii
url https://doi.org/10.1038/s41598-024-81501-z
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