The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites
ABSTRACT The Helicobacter pylori chemoreceptor TlpA plays a role in dampening host inflammation during chronic stomach colonization. TlpA has a periplasmic dCache_1 domain, a structure that is capable of sensing many ligands; however, the only characterized TlpA signals are arginine, bicarbonate, an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2021-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01819-21 |
| _version_ | 1818834124148834304 |
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| author | Kevin S. Johnson Bassam A. Elgamoudi Freda E.-C. Jen Christopher J. Day Emily Goers Sweeney Megan L. Pryce Karen Guillemin Thomas Haselhorst Victoria Korolik Karen M. Ottemann |
| author_facet | Kevin S. Johnson Bassam A. Elgamoudi Freda E.-C. Jen Christopher J. Day Emily Goers Sweeney Megan L. Pryce Karen Guillemin Thomas Haselhorst Victoria Korolik Karen M. Ottemann |
| author_sort | Kevin S. Johnson |
| collection | DOAJ |
| description | ABSTRACT The Helicobacter pylori chemoreceptor TlpA plays a role in dampening host inflammation during chronic stomach colonization. TlpA has a periplasmic dCache_1 domain, a structure that is capable of sensing many ligands; however, the only characterized TlpA signals are arginine, bicarbonate, and acid. To increase our understanding of TlpA’s sensing profile, we screened for diverse TlpA ligands using ligand binding arrays. TlpA bound seven ligands with affinities in the low- to middle-micromolar ranges. Three of these ligands, arginine, fumarate, and cysteine, were TlpA-dependent chemoattractants, while the others elicited no response. Molecular docking experiments, site-directed point mutants, and competition surface plasmon resonance binding assays suggested that TlpA binds ligands via both the membrane-distal and -proximal dCache_1 binding pockets. Surprisingly, one of the nonactive ligands, glucosamine, acted as a chemotaxis antagonist, preventing the chemotaxis response to chemoattractant ligands, and acted to block the binding of ligands irrespective of whether they bound the membrane-distal or -proximal dCache_1 subdomains. In total, these results suggest that TlpA senses multiple attractant ligands as well as antagonist ones, an emerging theme in chemotaxis systems. IMPORTANCE Numerous chemotactic bacterial pathogens depend on the ability to sense a diverse array of signals through chemoreceptors to achieve successful colonization and virulence within their host. The signals sensed by chemoreceptors, however, are not always fully understood. This is the case for TlpA, a dCache_1 chemoreceptor of H. pylori that enables the bacterium to induce less inflammation during chronic infections. H. pylori causes a significant global disease burden, which is driven by the development of gastric inflammation. Accordingly, it is essential to understand the processes by which H. pylori modulates host inflammation. This work uncovers the signals that TlpA can sense and highlights the underappreciated ability to regulate chemotactic responses by antagonistic chemoreceptor ligands, which is an emerging theme among other chemotactic systems. |
| first_indexed | 2024-12-19T02:29:49Z |
| format | Article |
| id | doaj.art-958587dd065b4f2d967bac45ac018790 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T02:29:49Z |
| publishDate | 2021-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-958587dd065b4f2d967bac45ac0187902022-12-21T20:39:42ZengAmerican Society for MicrobiologymBio2150-75112021-08-0112410.1128/mBio.01819-21The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct SitesKevin S. Johnson0Bassam A. Elgamoudi1Freda E.-C. Jen2Christopher J. Day3Emily Goers Sweeney4Megan L. Pryce5Karen Guillemin6Thomas Haselhorst7Victoria Korolik8Karen M. Ottemann9Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USAInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, AustraliaInstitute of Molecular Biology, University of Oregon, Eugene, Oregon, USADepartment of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USAInstitute of Molecular Biology, University of Oregon, Eugene, Oregon, USAInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, AustraliaDepartment of Microbiology and Environmental Toxicology, University of California, Santa Cruz, California, USAABSTRACT The Helicobacter pylori chemoreceptor TlpA plays a role in dampening host inflammation during chronic stomach colonization. TlpA has a periplasmic dCache_1 domain, a structure that is capable of sensing many ligands; however, the only characterized TlpA signals are arginine, bicarbonate, and acid. To increase our understanding of TlpA’s sensing profile, we screened for diverse TlpA ligands using ligand binding arrays. TlpA bound seven ligands with affinities in the low- to middle-micromolar ranges. Three of these ligands, arginine, fumarate, and cysteine, were TlpA-dependent chemoattractants, while the others elicited no response. Molecular docking experiments, site-directed point mutants, and competition surface plasmon resonance binding assays suggested that TlpA binds ligands via both the membrane-distal and -proximal dCache_1 binding pockets. Surprisingly, one of the nonactive ligands, glucosamine, acted as a chemotaxis antagonist, preventing the chemotaxis response to chemoattractant ligands, and acted to block the binding of ligands irrespective of whether they bound the membrane-distal or -proximal dCache_1 subdomains. In total, these results suggest that TlpA senses multiple attractant ligands as well as antagonist ones, an emerging theme in chemotaxis systems. IMPORTANCE Numerous chemotactic bacterial pathogens depend on the ability to sense a diverse array of signals through chemoreceptors to achieve successful colonization and virulence within their host. The signals sensed by chemoreceptors, however, are not always fully understood. This is the case for TlpA, a dCache_1 chemoreceptor of H. pylori that enables the bacterium to induce less inflammation during chronic infections. H. pylori causes a significant global disease burden, which is driven by the development of gastric inflammation. Accordingly, it is essential to understand the processes by which H. pylori modulates host inflammation. This work uncovers the signals that TlpA can sense and highlights the underappreciated ability to regulate chemotactic responses by antagonistic chemoreceptor ligands, which is an emerging theme among other chemotactic systems.https://journals.asm.org/doi/10.1128/mBio.01819-21Helicobacter pylorichemotaxisligand discoverydCachesignal transductionchemoreceptor |
| spellingShingle | Kevin S. Johnson Bassam A. Elgamoudi Freda E.-C. Jen Christopher J. Day Emily Goers Sweeney Megan L. Pryce Karen Guillemin Thomas Haselhorst Victoria Korolik Karen M. Ottemann The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites mBio Helicobacter pylori chemotaxis ligand discovery dCache signal transduction chemoreceptor |
| title | The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites |
| title_full | The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites |
| title_fullStr | The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites |
| title_full_unstemmed | The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites |
| title_short | The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites |
| title_sort | dcache chemoreceptor tlpa of named content content type genus species helicobacter pylori named content binds multiple attractant and antagonistic ligands via distinct sites |
| topic | Helicobacter pylori chemotaxis ligand discovery dCache signal transduction chemoreceptor |
| url | https://journals.asm.org/doi/10.1128/mBio.01819-21 |
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