Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways
Abstract Background Metabolite production is essential for the proliferation and environmental adaptation of all living organisms. In pathogenic bacteria, metabolite exchange during host infection can regulate their physiology and virulence. However, there is still much unknown about which specific...
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BMC
2025-02-01
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| Series: | BMC Microbiology |
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| Online Access: | https://doi.org/10.1186/s12866-024-03654-1 |
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| author | Ho Seok Sim Yong-Kook Kwon Hokyung Song Geum-Sook Hwang Jinki Yeom |
| author_facet | Ho Seok Sim Yong-Kook Kwon Hokyung Song Geum-Sook Hwang Jinki Yeom |
| author_sort | Ho Seok Sim |
| collection | DOAJ |
| description | Abstract Background Metabolite production is essential for the proliferation and environmental adaptation of all living organisms. In pathogenic bacteria, metabolite exchange during host infection can regulate their physiology and virulence. However, there is still much unknown about which specific metabolic pathways in pathogenic bacteria respond to changes in the environment during infections. This study examines how pathogenic bacterium Acinetobacter baumannii uses particular metabolic pathways to regulate its ability to antibiotic persistence and pathogenesis. Results To determine specific metabolic pathways in pathogenic antibiotic resistance bacteria, metabolite profiles of bacteria were constructed using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry and multivariate statistical analysis. A. baumannii generates amino acid derivative metabolites, which are precursors for fatty acid production. Comparative genomic analysis identified specific genes regulating the production of these metabolites and fatty acids in A. baumannii. Inactivation of genes involved in glutamate metabolism, gdhA, aspB, murI1, and racD, impairs antibiotic persistence, while inactivation of the hisC gene, encoding histidinol − phosphate aminotransferase enzyme in histidine metabolic pathway, increases bacterial survival inside macrophages during infections. Conclusions This study reports that A. baumannii regulates antibiotic persistence and pathogenesis through glutamate and histidine metabolic pathways, respectively. These findings suggest that specific metabolic pathways regulate bacterial pathogenesis and antibiotic persistence during infections, providing potential therapeutic targets for pathogenic bacteria. |
| format | Article |
| id | doaj-art-c3f306233bdd4be4ab6f3e647b40db75 |
| institution | DOAJ |
| issn | 1471-2180 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj-art-c3f306233bdd4be4ab6f3e647b40db752025-08-20T02:48:29ZengBMCBMC Microbiology1471-21802025-02-0125111410.1186/s12866-024-03654-1Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathwaysHo Seok Sim0Yong-Kook Kwon1Hokyung Song2Geum-Sook Hwang3Jinki Yeom4Department of Biomedical Science, College of Medicine, Seoul National UniversityIntegrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science InstituteDepartment of Environmental Engineering, Chosun UniversityIntegrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science InstituteDepartment of Biomedical Science, College of Medicine, Seoul National UniversityAbstract Background Metabolite production is essential for the proliferation and environmental adaptation of all living organisms. In pathogenic bacteria, metabolite exchange during host infection can regulate their physiology and virulence. However, there is still much unknown about which specific metabolic pathways in pathogenic bacteria respond to changes in the environment during infections. This study examines how pathogenic bacterium Acinetobacter baumannii uses particular metabolic pathways to regulate its ability to antibiotic persistence and pathogenesis. Results To determine specific metabolic pathways in pathogenic antibiotic resistance bacteria, metabolite profiles of bacteria were constructed using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry and multivariate statistical analysis. A. baumannii generates amino acid derivative metabolites, which are precursors for fatty acid production. Comparative genomic analysis identified specific genes regulating the production of these metabolites and fatty acids in A. baumannii. Inactivation of genes involved in glutamate metabolism, gdhA, aspB, murI1, and racD, impairs antibiotic persistence, while inactivation of the hisC gene, encoding histidinol − phosphate aminotransferase enzyme in histidine metabolic pathway, increases bacterial survival inside macrophages during infections. Conclusions This study reports that A. baumannii regulates antibiotic persistence and pathogenesis through glutamate and histidine metabolic pathways, respectively. These findings suggest that specific metabolic pathways regulate bacterial pathogenesis and antibiotic persistence during infections, providing potential therapeutic targets for pathogenic bacteria.https://doi.org/10.1186/s12866-024-03654-1Acinetobacter baumanniiAntibiotic persistencePathogenesisMetabolomicsMetabolic pathways |
| spellingShingle | Ho Seok Sim Yong-Kook Kwon Hokyung Song Geum-Sook Hwang Jinki Yeom Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways BMC Microbiology Acinetobacter baumannii Antibiotic persistence Pathogenesis Metabolomics Metabolic pathways |
| title | Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways |
| title_full | Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways |
| title_fullStr | Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways |
| title_full_unstemmed | Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways |
| title_short | Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways |
| title_sort | regulation of antibiotic persistence and pathogenesis in acinetobacter baumannii by glutamate and histidine metabolic pathways |
| topic | Acinetobacter baumannii Antibiotic persistence Pathogenesis Metabolomics Metabolic pathways |
| url | https://doi.org/10.1186/s12866-024-03654-1 |
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