دورية أكاديمية
Methylthioadenosine suppresses Salmonella virulence
| العنوان: | Methylthioadenosine suppresses Salmonella virulence |
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| المؤلفون: | Bourgeois, JS, Zhou, D, Thurston, TLM, Gilchrist, JJ, Ko, DC |
| المساهمون: | Wellcome Trust |
| بيانات النشر: | American Society for Microbiology |
| سنة النشر: | 2018 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, SPI-1, Salmonella, flagellar motility, inflammation, metJ, metabolism, methionine salvage, methylthioadenosine, virulence regulation, ENTERICA SEROVAR TYPHIMURIUM, STATE ANALOG INHIBITORS, SAH/MTA NUCLEOSIDASE INHIBITORS, STRUCTURE-BASED DESIGN, ESCHERICHIA-COLI, GENE-EXPRESSION, INVASION GENES, 5'-METHYLTHIOADENOSINE PHOSPHORYLASE, ANTIMICROBIAL ACTIVITY, MACROPHAGE APOPTOSIS, 06 Biological Sciences, 11 Medical And Health Sciences, 07 Agricultural And Veterinary Sciences, Microbiology |
| جغرافية الموضوع: | United States |
| الوصف: | In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously we showed transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) in serum during systemic Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. Here we explored the functional consequences of increased MTA concentrations on S. Typhimurium virulence. We found that MTA-but not other related metabolites involved in polyamine synthesis and methionine salvage-reduced motility, host cell pyroptosis, and cellular invasion. Further, we developed a genetic model of increased bacterial endogenous MTA production by knocking out the master repressor of the methionine regulon, metJ Like MTA-treated S. Typhimurium, the ΔmetJ mutant displayed reduced motility, host cell pyroptosis, and invasion. These phenotypic effects of MTA correlated with suppression of flagellar and Salmonella pathogenicity island-1 (SPI-1) networks. ΔmetJ S. Typhimurium had reduced virulence in oral and intraperitoneal infection of C57BL/6J mice, independently of the effects of MTA on SPI-1. Finally, ΔmetJ bacteria induced a less severe inflammatory cytokine response in a mouse sepsis model. Together, these data indicate that exposure of S. Typhimurium to MTA or disruption of the bacterial methionine metabolism pathway suppresses S. Typhimurium virulence. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0019-9567 |
| العلاقة: | Infection and Immunity; http://hdl.handle.net/10044/1/62765Test; https://dx.doi.org/10.1128/IAI.00429-18Test; 097816/Z/11/B |
| DOI: | 10.1128/IAI.00429-18 |
| الإتاحة: | https://doi.org/10.1128/IAI.00429-18Test http://hdl.handle.net/10044/1/62765Test |
| حقوق: | © 2018 Bourgeois et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0Test/). |
| رقم الانضمام: | edsbas.1FA63ED1 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00199567 |
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| DOI: | 10.1128/IAI.00429-18 |