In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study
Lingjun Wen, Can Luo, Xinyi Chen, Tianyao Liu, Xianping Li,* Min Wang* Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Wang; Xian...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-09-01
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| Series: | Infection and Drug Resistance |
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| Online Access: | https://www.dovepress.com/in-vitro-activity-of-cefepimeavibactam-against-carbapenem-resistant-kl-peer-reviewed-fulltext-article-IDR |
| _version_ | 1797685531213037568 |
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| author | Wen L Luo C Chen X Liu T Li X Wang M |
| author_facet | Wen L Luo C Chen X Liu T Li X Wang M |
| author_sort | Wen L |
| collection | DOAJ |
| description | Lingjun Wen, Can Luo, Xinyi Chen, Tianyao Liu, Xianping Li,* Min Wang* Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Wang; Xianping Li, Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, People’s Republic of China, Tel +86 13298697558, Email wangmin0000@csu.edu.cn; xianpingli2017@csu.edu.cnPurpose: We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI.Patients and Methods: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI.Results: FEP/AVI (MIC50/MIC90 0.5/4-64/4 μg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC50/MIC90 4/4-128/4 μg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes (adhE, gltB, purA, ftsI and hns) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP.Conclusion: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae.Keywords: carbapenem-resistantKlebsiella pneumoniae, bacterial resistance, proteomics, metabolomics, cefepime/avibactam, ribosome |
| first_indexed | 2024-03-12T00:45:31Z |
| format | Article |
| id | doaj.art-ccd34816c0f340cc9418a347d1afcb14 |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-03-12T00:45:31Z |
| publishDate | 2023-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-ccd34816c0f340cc9418a347d1afcb142023-09-14T19:09:01ZengDove Medical PressInfection and Drug Resistance1178-69732023-09-01Volume 166061607786600In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center StudyWen LLuo CChen XLiu TLi XWang MLingjun Wen, Can Luo, Xinyi Chen, Tianyao Liu, Xianping Li,* Min Wang* Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Wang; Xianping Li, Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, People’s Republic of China, Tel +86 13298697558, Email wangmin0000@csu.edu.cn; xianpingli2017@csu.edu.cnPurpose: We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI.Patients and Methods: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI.Results: FEP/AVI (MIC50/MIC90 0.5/4-64/4 μg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC50/MIC90 4/4-128/4 μg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes (adhE, gltB, purA, ftsI and hns) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP.Conclusion: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae.Keywords: carbapenem-resistantKlebsiella pneumoniae, bacterial resistance, proteomics, metabolomics, cefepime/avibactam, ribosomehttps://www.dovepress.com/in-vitro-activity-of-cefepimeavibactam-against-carbapenem-resistant-kl-peer-reviewed-fulltext-article-IDRcarbapenem-resistant klebsiella pneumoniaebacterial resistanceproteomicsmetabolomicscefepime/avibactam；ribosome. |
| spellingShingle | Wen L Luo C Chen X Liu T Li X Wang M In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study Infection and Drug Resistance carbapenem-resistant klebsiella pneumoniae bacterial resistance proteomics metabolomics cefepime/avibactam；ribosome. |
| title | In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study |
| title_full | In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study |
| title_fullStr | In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study |
| title_full_unstemmed | In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study |
| title_short | In vitro Activity of Cefepime/Avibactam Against Carbapenem Resistant Klebsiella pneumoniae and Integrative Metabolomics-Proteomics Approach for Resistance Mechanism: A Single-Center Study |
| title_sort | in vitro activity of cefepime avibactam against carbapenem resistant klebsiella pneumoniae and integrative metabolomics proteomics approach for resistance mechanism a single center study |
| topic | carbapenem-resistant klebsiella pneumoniae bacterial resistance proteomics metabolomics cefepime/avibactam；ribosome. |
| url | https://www.dovepress.com/in-vitro-activity-of-cefepimeavibactam-against-carbapenem-resistant-kl-peer-reviewed-fulltext-article-IDR |
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