Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish
IntroductionMetabolic reprogramming potentiates host protection against antibiotic-sensitive or -resistant bacteria. However, it remains unclear whether a single reprogramming metabolite is effective enough to combat both antibiotic-sensitive and -resistant bacteria. This knowledge is key for implem...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277281/full |
| _version_ | 1827795754054320128 |
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| author | Jiao Xiang Min-yi Li Hui Li Hui Li Hui Li Hui Li |
| author_facet | Jiao Xiang Min-yi Li Hui Li Hui Li Hui Li Hui Li |
| author_sort | Jiao Xiang |
| collection | DOAJ |
| description | IntroductionMetabolic reprogramming potentiates host protection against antibiotic-sensitive or -resistant bacteria. However, it remains unclear whether a single reprogramming metabolite is effective enough to combat both antibiotic-sensitive and -resistant bacteria. This knowledge is key for implementing an antibiotic-free approach.MethodsThe reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistant Edwardsiella tarda and to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite.ResultsAspartate was identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. Exogenous aspartate protects zebrafish against infection caused by tetracycline-sensitive and -resistant E. tarda. Mechanistically, exogenous aspartate promotes nitric oxide (NO) biosynthesis. NO is a well-documented factor of promoting innate immunity against bacteria, but whether it can play a role in eliminating both tetracycline-sensitive and -resistant E. tarda is unknown. Thus, in this study, aspartate was replaced with sodium nitroprusside to provide NO, which led to similar aspartate-induced protection against tetracycline-sensitive and -resistant E. tarda.DiscussionThese findings support the conclusion that aspartate plays an important protective role through NO against both types of E. tarda. Importantly, we found that tetracycline-sensitive and -resistant E. tarda are sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens. |
| first_indexed | 2024-03-11T18:54:57Z |
| format | Article |
| id | doaj.art-ce0bba08f5ef4cbf86a5421af757c9e7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T18:54:57Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ce0bba08f5ef4cbf86a5421af757c9e72023-10-11T06:54:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12772811277281Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafishJiao Xiang0Min-yi Li1Hui Li2Hui Li3Hui Li4Hui Li5State Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaLaboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, ChinaGuangdong Province Key Laboratory for Pharmaceutical Functional Genes, Sun Yat-sen University, Guangzhou, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou, ChinaIntroductionMetabolic reprogramming potentiates host protection against antibiotic-sensitive or -resistant bacteria. However, it remains unclear whether a single reprogramming metabolite is effective enough to combat both antibiotic-sensitive and -resistant bacteria. This knowledge is key for implementing an antibiotic-free approach.MethodsThe reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistant Edwardsiella tarda and to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite.ResultsAspartate was identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. Exogenous aspartate protects zebrafish against infection caused by tetracycline-sensitive and -resistant E. tarda. Mechanistically, exogenous aspartate promotes nitric oxide (NO) biosynthesis. NO is a well-documented factor of promoting innate immunity against bacteria, but whether it can play a role in eliminating both tetracycline-sensitive and -resistant E. tarda is unknown. Thus, in this study, aspartate was replaced with sodium nitroprusside to provide NO, which led to similar aspartate-induced protection against tetracycline-sensitive and -resistant E. tarda.DiscussionThese findings support the conclusion that aspartate plays an important protective role through NO against both types of E. tarda. Importantly, we found that tetracycline-sensitive and -resistant E. tarda are sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277281/fullEdwardsiella tardaaspartatenitric oxidereprogramming metabolomeantibiotic-free approachzebrafish |
| spellingShingle | Jiao Xiang Min-yi Li Hui Li Hui Li Hui Li Hui Li Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish Frontiers in Immunology Edwardsiella tarda aspartate nitric oxide reprogramming metabolome antibiotic-free approach zebrafish |
| title | Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish |
| title_full | Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish |
| title_fullStr | Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish |
| title_full_unstemmed | Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish |
| title_short | Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant Edwardsiella tarda in zebrafish |
| title_sort | aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic sensitive and resistant edwardsiella tarda in zebrafish |
| topic | Edwardsiella tarda aspartate nitric oxide reprogramming metabolome antibiotic-free approach zebrafish |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277281/full |
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