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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Helicobacter pylori chemotaxis ligand discovery dCache signal transduction chemoreceptor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/958587dd065b4f2d967bac45ac018790
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spelling	oai:doaj.org-article:958587dd065b4f2d967bac45ac0187902021-11-10T18:37:52ZThe dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites10.1128/mBio.01819-212150-7511https://doaj.org/article/958587dd065b4f2d967bac45ac0187902021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01819-21https://doaj.org/toc/2150-7511ABSTRACT 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.Kevin S. JohnsonBassam A. ElgamoudiFreda E.-C. JenChristopher J. DayEmily Goers SweeneyMegan L. PryceKaren GuilleminThomas HaselhorstVictoria KorolikKaren M. OttemannAmerican Society for MicrobiologyarticleHelicobacter pylorichemotaxisligand discoverydCachesignal transductionchemoreceptorMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Helicobacter pylori chemotaxis ligand discovery dCache signal transduction chemoreceptor Microbiology QR1-502
spellingShingle	Helicobacter pylori chemotaxis ligand discovery dCache signal transduction chemoreceptor Microbiology QR1-502 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
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.
format	article
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
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_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_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_sort	dcache chemoreceptor tlpa of <named-content content-type="genus-species">helicobacter pylori</named-content> binds multiple attractant and antagonistic ligands via distinct sites
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/958587dd065b4f2d967bac45ac018790
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The dCache Chemoreceptor TlpA of <named-content content-type="genus-species">Helicobacter pylori</named-content> Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites

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