Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines
Abstract Chronic inflammation induced by Helicobacter pylori is strongly associated with gastric cancer development, which is influenced by both bacterial virulence and host genetics. The sialic acid-binding adhesin SabA and the MUC5AC-binding adhesin LabA are important H. pylori virulence factors t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24311-5 |
| _version_ | 1811304614678495232 |
|---|---|
| author | Tanvi Somiah Hanna G. Gebremariam Fanglei Zuo Ksenija Smirnova Ann-Beth Jonsson |
| author_facet | Tanvi Somiah Hanna G. Gebremariam Fanglei Zuo Ksenija Smirnova Ann-Beth Jonsson |
| author_sort | Tanvi Somiah |
| collection | DOAJ |
| description | Abstract Chronic inflammation induced by Helicobacter pylori is strongly associated with gastric cancer development, which is influenced by both bacterial virulence and host genetics. The sialic acid-binding adhesin SabA and the MUC5AC-binding adhesin LabA are important H. pylori virulence factors that facilitate adhesion of the bacterium, which is a crucial step in colonization. Lactate utilization has been reported to play a key role in the pathogenicity of different bacterial species. However, this is poorly understood in H. pylori. In this study, we investigated the effect of lactate on H. pylori adhesin gene expression and the regulation of host inflammatory cytokines. We show that the bacterial adhesins SabA and LabA were downregulated at the transcriptional level during incubation of H. pylori with lactate. Downregulation of sabA required the involvement of the two-component system ArsRS, while labA was regulated via the CheA/CheY system, indicating differences in the regulation of these genes in response to lactate. The levels of the proinflammatory cytokines TNF and IL-6 in H. pylori-stimulated macrophages were reduced when lactate was present. Interestingly, glucose did not prevent the secretion of these cytokines. Taken together, our data suggest that lactate affects H. pylori adhesin gene expression and the host response upon infection. |
| first_indexed | 2024-04-13T08:10:35Z |
| format | Article |
| id | doaj.art-963254c383a54e2c931317fbc283a7f9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T08:10:35Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-963254c383a54e2c931317fbc283a7f92022-12-22T02:55:02ZengNature PortfolioScientific Reports2045-23222022-11-0112111310.1038/s41598-022-24311-5Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokinesTanvi Somiah0Hanna G. Gebremariam1Fanglei Zuo2Ksenija Smirnova3Ann-Beth Jonsson4Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityAbstract Chronic inflammation induced by Helicobacter pylori is strongly associated with gastric cancer development, which is influenced by both bacterial virulence and host genetics. The sialic acid-binding adhesin SabA and the MUC5AC-binding adhesin LabA are important H. pylori virulence factors that facilitate adhesion of the bacterium, which is a crucial step in colonization. Lactate utilization has been reported to play a key role in the pathogenicity of different bacterial species. However, this is poorly understood in H. pylori. In this study, we investigated the effect of lactate on H. pylori adhesin gene expression and the regulation of host inflammatory cytokines. We show that the bacterial adhesins SabA and LabA were downregulated at the transcriptional level during incubation of H. pylori with lactate. Downregulation of sabA required the involvement of the two-component system ArsRS, while labA was regulated via the CheA/CheY system, indicating differences in the regulation of these genes in response to lactate. The levels of the proinflammatory cytokines TNF and IL-6 in H. pylori-stimulated macrophages were reduced when lactate was present. Interestingly, glucose did not prevent the secretion of these cytokines. Taken together, our data suggest that lactate affects H. pylori adhesin gene expression and the host response upon infection.https://doi.org/10.1038/s41598-022-24311-5 |
| spellingShingle | Tanvi Somiah Hanna G. Gebremariam Fanglei Zuo Ksenija Smirnova Ann-Beth Jonsson Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines Scientific Reports |
| title | Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines |
| title_full | Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines |
| title_fullStr | Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines |
| title_full_unstemmed | Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines |
| title_short | Lactate causes downregulation of Helicobacter pylori adhesin genes sabA and labA while dampening the production of proinflammatory cytokines |
| title_sort | lactate causes downregulation of helicobacter pylori adhesin genes saba and laba while dampening the production of proinflammatory cytokines |
| url | https://doi.org/10.1038/s41598-022-24311-5 |
| work_keys_str_mv | AT tanvisomiah lactatecausesdownregulationofhelicobacterpyloriadhesingenessabaandlabawhiledampeningtheproductionofproinflammatorycytokines AT hannaggebremariam lactatecausesdownregulationofhelicobacterpyloriadhesingenessabaandlabawhiledampeningtheproductionofproinflammatorycytokines AT fangleizuo lactatecausesdownregulationofhelicobacterpyloriadhesingenessabaandlabawhiledampeningtheproductionofproinflammatorycytokines AT ksenijasmirnova lactatecausesdownregulationofhelicobacterpyloriadhesingenessabaandlabawhiledampeningtheproductionofproinflammatorycytokines AT annbethjonsson lactatecausesdownregulationofhelicobacterpyloriadhesingenessabaandlabawhiledampeningtheproductionofproinflammatorycytokines |