L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently
ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) can colonize the gastrointestinal tract and cause bloody diarrhea in children. Previous studies showed that its pathogenesis could be mediated by metabolites from both the host and microbiota. L-Glutamine (Gln) was found to be depleted in intestinal...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-12-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00975-23 |
| _version_ | 1797393704515796992 |
|---|---|
| author | Fang Fang Yunxin Xue Xuefang Xu Dingli Fang Weijia Liu Ying Zhong Jinping Han Yunhe Li Qian Tao Rong Lu Cong Ma Arvind Kumar Dai Wang |
| author_facet | Fang Fang Yunxin Xue Xuefang Xu Dingli Fang Weijia Liu Ying Zhong Jinping Han Yunhe Li Qian Tao Rong Lu Cong Ma Arvind Kumar Dai Wang |
| author_sort | Fang Fang |
| collection | DOAJ |
| description | ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) can colonize the gastrointestinal tract and cause bloody diarrhea in children. Previous studies showed that its pathogenesis could be mediated by metabolites from both the host and microbiota. L-Glutamine (Gln) was found to be depleted in intestinal tissues as the main energy source according to previous studies. Hence, we aimed to determine the effects of Gln on EHEC infection and its underlying mode of action. In this study, a Gln-limited signal was found to activate the type 3 secretion system (T3SS), which is crucial for EHEC infection via perturbation of central metabolism. By shifting the phosphorylation of NtrC, a key regulator in bacterial nitrogen metabolism, Gln stimulates ler transcripts in a σS-PchA-dependent manner. Our in vivo experiments further demonstrated that Gln supplementation can reduce EHEC colonization in the gastrointestinal tract by repressing T3SS. Moreover, Gln could further attenuate bacterial infection by boosting host defense, which might be dependent on multiple pathways. Besides, our experiments demonstrated that Gln did not induce Shiga-like toxin (Stx) production or cause impairment of gut flora. In conclusion, our study presented evidence that Gln could act against EHEC infection by reducing bacterial virulence and strengthening host defense. Therefore, Gln serves as a promising therapeutic agent for EHEC infection. IMPORTANCE The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic Escherichia coli (EHEC) T3SS expression via nitrogen metabolism and therefore had potential as an antivirulence agent. Our in vitro and in vivo evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly. |
| first_indexed | 2024-03-09T00:06:44Z |
| format | Article |
| id | doaj.art-eb350c9bbb484dd68d47e98cc3d032fc |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:44Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-eb350c9bbb484dd68d47e98cc3d032fc2023-12-12T13:17:18ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.00975-23L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrentlyFang Fang0Yunxin Xue1Xuefang Xu2Dingli Fang3Weijia Liu4Ying Zhong5Jinping Han6Yunhe Li7Qian Tao8Rong Lu9Cong Ma10Arvind Kumar11Dai Wang12Department of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaState Key Laboratory of Infectious Disease Prevention and Control and National Institute for Communicable Diseases Control and Prevention, Chinese Center for Disease Control and Prevention , Changping, Beijing, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Pathology, Women and Children's Hospital, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaDepartment of Nephrology, Lishan Hospital, Anshan Central Hospital , Anshan, Liaoning Province, ChinaBiomEdit , Fishers, Indiana, USADepartment of Laboratory Medicine, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Women and Children's Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedical Laboratory, School of Public Health and School of Medicine, Xiamen University , Xiamen, Fujian Province, ChinaABSTRACT Enterohemorrhagic Escherichia coli (EHEC) can colonize the gastrointestinal tract and cause bloody diarrhea in children. Previous studies showed that its pathogenesis could be mediated by metabolites from both the host and microbiota. L-Glutamine (Gln) was found to be depleted in intestinal tissues as the main energy source according to previous studies. Hence, we aimed to determine the effects of Gln on EHEC infection and its underlying mode of action. In this study, a Gln-limited signal was found to activate the type 3 secretion system (T3SS), which is crucial for EHEC infection via perturbation of central metabolism. By shifting the phosphorylation of NtrC, a key regulator in bacterial nitrogen metabolism, Gln stimulates ler transcripts in a σS-PchA-dependent manner. Our in vivo experiments further demonstrated that Gln supplementation can reduce EHEC colonization in the gastrointestinal tract by repressing T3SS. Moreover, Gln could further attenuate bacterial infection by boosting host defense, which might be dependent on multiple pathways. Besides, our experiments demonstrated that Gln did not induce Shiga-like toxin (Stx) production or cause impairment of gut flora. In conclusion, our study presented evidence that Gln could act against EHEC infection by reducing bacterial virulence and strengthening host defense. Therefore, Gln serves as a promising therapeutic agent for EHEC infection. IMPORTANCE The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic Escherichia coli (EHEC) T3SS expression via nitrogen metabolism and therefore had potential as an antivirulence agent. Our in vitro and in vivo evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly.https://journals.asm.org/doi/10.1128/spectrum.00975-23enterohemorrhagic Escherichia coliL-glutaminenitrogen metabolismtype 3 secretion systemantivirulencehost defense |
| spellingShingle | Fang Fang Yunxin Xue Xuefang Xu Dingli Fang Weijia Liu Ying Zhong Jinping Han Yunhe Li Qian Tao Rong Lu Cong Ma Arvind Kumar Dai Wang L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently Microbiology Spectrum enterohemorrhagic Escherichia coli L-glutamine nitrogen metabolism type 3 secretion system antivirulence host defense |
| title | L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently |
| title_full | L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently |
| title_fullStr | L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently |
| title_full_unstemmed | L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently |
| title_short | L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently |
| title_sort | l glutamine protects against enterohemorrhagic escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently |
| topic | enterohemorrhagic Escherichia coli L-glutamine nitrogen metabolism type 3 secretion system antivirulence host defense |
| url | https://journals.asm.org/doi/10.1128/spectrum.00975-23 |
| work_keys_str_mv | AT fangfang lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT yunxinxue lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT xuefangxu lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT dinglifang lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT weijialiu lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT yingzhong lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT jinpinghan lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT yunheli lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT qiantao lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT ronglu lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT congma lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT arvindkumar lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently AT daiwang lglutamineprotectsagainstenterohemorrhagicescherichiacoliinfectionbyinhibitingbacterialvirulenceandenhancinghostdefenseconcurrently |