Glutamine Potentiates Cefoperazone-Sulbactam against by Enhancing Cellular Uptake and ROS Production.
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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ACS infectious diseases
2026
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| author | Li, Shao-Hua Chen, Yu-Yan Fu, Huan-Zhe Lin, Hui-Yin Tao, Yuan Zhao, Xian-Liang Chen, Yue-Tao Xiang, Jiao Zeng, Ying-Yue Wang, Shi-Wen Wu, Kui-Hai Shi, Zheng-Qi Tang, Jin Huang, Xiao-Xia Wang, Xin Li, Hui Lin, Li-Rong Peng, Xuan-Xian |
| author_facet | Li, Shao-Hua Chen, Yu-Yan Fu, Huan-Zhe Lin, Hui-Yin Tao, Yuan Zhao, Xian-Liang Chen, Yue-Tao Xiang, Jiao Zeng, Ying-Yue Wang, Shi-Wen Wu, Kui-Hai Shi, Zheng-Qi Tang, Jin Huang, Xiao-Xia Wang, Xin Li, Hui Lin, Li-Rong Peng, Xuan-Xian Li, Shao-Hua Chen, Yu-Yan Fu, Huan-Zhe Lin, Hui-Yin Tao, Yuan Zhao, Xian-Liang Chen, Yue-Tao Xiang, Jiao Zeng, Ying-Yue Wang, Shi-Wen Wu, Kui-Hai Shi, Zheng-Qi Tang, Jin Huang, Xiao-Xia Wang, Xin Li, Hui Lin, Li-Rong Peng, Xuan-Xian |
| collection | PubMed - marine biology |
| contents | Glutamine Potentiates Cefoperazone-Sulbactam against by Enhancing Cellular Uptake and ROS Production. Li, Shao-Hua Chen, Yu-Yan Fu, Huan-Zhe Lin, Hui-Yin Tao, Yuan Zhao, Xian-Liang Chen, Yue-Tao Xiang, Jiao Zeng, Ying-Yue Wang, Shi-Wen Wu, Kui-Hai Shi, Zheng-Qi Tang, Jin Huang, Xiao-Xia Wang, Xin Li, Hui Lin, Li-Rong Peng, Xuan-Xian Klebsiella pneumoniae Cefoperazone Reactive Oxygen Species Animals Glutamine Sulbactam Klebsiella Infections Mice Microbial Sensitivity Tests Anti-Bacterial Agents Drug Synergism Drug Resistance, Multiple, Bacterial Humans Antibiotic-resistant poses a serious global challenge to clinical practice and public health, highlighting an urgent need for effective therapeutic strategies. This study systematically evaluated the preclinical pharmacodynamics of cefoperazone-sulbactam (SCF) in combination with glutamine against . Clinically isolated strains were classified into three groups: 56 sensitive (S-KP), 62 multidrug-resistant but carbapenem-sensitive (MDR-KP), and 195 multidrug-resistant and carbapenem-resistant (CR-KP) isolates. Compared with SCF alone, the combination with glutamine enhanced bacterial killing in 95.85% of the tested isolates. This potentiation was further confirmed by time-kill kinetic assays and a murine infection model, with results showing consistent efficacy independent of pH and calcium levels but dependent on bacterial inoculum. Moreover, glutamine delayed the increase in the minimum inhibitory concentration of SCF, extended its postantibiotic effect, and reduced the mutation frequency. Mechanistically, glutamine overcomes antibiotic resistance by reprogramming bacterial metabolism to promote cefoperazone uptake and elevate reactive oxygen species (ROS) production. Increased intracellular drug levels counteract efflux- and hydrolysis-mediated defenses, while elevated ROS acts synergistically with the antibiotic, together resulting in enhanced bactericidal activity. This study demonstrates that glutamine enhances the activity of SCF against a broad range of pathogens, supporting its potential development as an adjuvant therapy for resistant infections. |
| format | Artículo científico |
| id | pubmed_42053167 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | ACS infectious diseases |
| record_format | pubmed |
| spellingShingle | Glutamine Potentiates Cefoperazone-Sulbactam against by Enhancing Cellular Uptake and ROS Production. Li, Shao-Hua Chen, Yu-Yan Fu, Huan-Zhe Lin, Hui-Yin Tao, Yuan Zhao, Xian-Liang Chen, Yue-Tao Xiang, Jiao Zeng, Ying-Yue Wang, Shi-Wen Wu, Kui-Hai Shi, Zheng-Qi Tang, Jin Huang, Xiao-Xia Wang, Xin Li, Hui Lin, Li-Rong Peng, Xuan-Xian Klebsiella pneumoniae Cefoperazone Reactive Oxygen Species Animals Glutamine Sulbactam Klebsiella Infections Mice Microbial Sensitivity Tests Anti-Bacterial Agents Drug Synergism Drug Resistance, Multiple, Bacterial Humans Glutamine Potentiates Cefoperazone-Sulbactam against by Enhancing Cellular Uptake and ROS Production. Li, Shao-Hua Chen, Yu-Yan Fu, Huan-Zhe Lin, Hui-Yin Tao, Yuan Zhao, Xian-Liang Chen, Yue-Tao Xiang, Jiao Zeng, Ying-Yue Wang, Shi-Wen Wu, Kui-Hai Shi, Zheng-Qi Tang, Jin Huang, Xiao-Xia Wang, Xin Li, Hui Lin, Li-Rong Peng, Xuan-Xian Klebsiella pneumoniae Cefoperazone Reactive Oxygen Species Animals Glutamine Sulbactam Klebsiella Infections Mice Microbial Sensitivity Tests Anti-Bacterial Agents Drug Synergism Drug Resistance, Multiple, Bacterial Humans Antibiotic-resistant poses a serious global challenge to clinical practice and public health, highlighting an urgent need for effective therapeutic strategies. This study systematically evaluated the preclinical pharmacodynamics of cefoperazone-sulbactam (SCF) in combination with glutamine against . Clinically isolated strains were classified into three groups: 56 sensitive (S-KP), 62 multidrug-resistant but carbapenem-sensitive (MDR-KP), and 195 multidrug-resistant and carbapenem-resistant (CR-KP) isolates. Compared with SCF alone, the combination with glutamine enhanced bacterial killing in 95.85% of the tested isolates. This potentiation was further confirmed by time-kill kinetic assays and a murine infection model, with results showing consistent efficacy independent of pH and calcium levels but dependent on bacterial inoculum. Moreover, glutamine delayed the increase in the minimum inhibitory concentration of SCF, extended its postantibiotic effect, and reduced the mutation frequency. Mechanistically, glutamine overcomes antibiotic resistance by reprogramming bacterial metabolism to promote cefoperazone uptake and elevate reactive oxygen species (ROS) production. Increased intracellular drug levels counteract efflux- and hydrolysis-mediated defenses, while elevated ROS acts synergistically with the antibiotic, together resulting in enhanced bactericidal activity. This study demonstrates that glutamine enhances the activity of SCF against a broad range of pathogens, supporting its potential development as an adjuvant therapy for resistant infections. |
| title | Glutamine Potentiates Cefoperazone-Sulbactam against by Enhancing Cellular Uptake and ROS Production. |
| topic | Klebsiella pneumoniae Cefoperazone Reactive Oxygen Species Animals Glutamine Sulbactam Klebsiella Infections Mice Microbial Sensitivity Tests Anti-Bacterial Agents Drug Synergism Drug Resistance, Multiple, Bacterial Humans |
| url | https://pubmed.ncbi.nlm.nih.gov/42053167/ |