A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>

ABSTRACT Trichomonas vaginalis, a prevalent sexually transmitted parasite, adheres to and induces cytolysis of human mucosal epithelial cells. We have characterized a hypothetical protein, TVAG_393390, with predicted tertiary structure similar to that of mammalian cadherin proteins involved in cell-...

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Autores principales:	Yi-Pei Chen, Angelica M. Riestra, Anand Kumar Rai, Patricia J. Johnson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Trichomonas vaginalis host-pathogen interactions parasite attachment Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e008584119374662bdcc4571afe08afc
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spelling	oai:doaj.org-article:e008584119374662bdcc4571afe08afc2021-11-15T15:55:25ZA Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>10.1128/mBio.00720-192150-7511https://doaj.org/article/e008584119374662bdcc4571afe08afc2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00720-19https://doaj.org/toc/2150-7511ABSTRACT Trichomonas vaginalis, a prevalent sexually transmitted parasite, adheres to and induces cytolysis of human mucosal epithelial cells. We have characterized a hypothetical protein, TVAG_393390, with predicted tertiary structure similar to that of mammalian cadherin proteins involved in cell-cell adherence. TVAG_393390, renamed cadherin-like protein (CLP), contains a calcium-binding site at a position conserved in cadherins. CLP is surface localized, and its mRNA and protein levels are significantly upregulated upon parasite adherence to host cells. To test the roles of CLP and its calcium-binding dependency during host cell adherence, we first demonstrated that wild-type CLP (CLP) binds calcium with a high affinity, whereas the calcium-binding site mutant protein (CLP-mut) does not. CLP and CLP-mut constructs were then used to overexpress these proteins in T. vaginalis. Parasites overexpressing CLP have ∼3.5-fold greater adherence to host cells than wild-type parasites, and this increased adherence is ablated by mutating the calcium-binding site. Additionally, competition with recombinant CLP decreased parasite binding to host cells. We also found that overexpression of CLP induced parasite aggregation which was further enhanced in the presence of calcium, whereas CLP-mut overexpression did not affect aggregation. Lastly, parasites overexpressing wild-type CLP induced killing of host cells ∼2.35-fold, whereas parasites overexpressing CLP-mut did not have this effect. These analyses describe the first parasitic CLP and demonstrate a role for this protein in mediating parasite-parasite and host-parasite interactions. T. vaginalis CLP may represent convergent evolution of a parasite protein that is functionally similar to the mammalian cell adhesion protein cadherin, which contributes to parasite pathogenesis. IMPORTANCE The adherence of pathogens to host cells is critical for colonization of the host and establishing infection. Here we identify a protein with no known function that is more abundant on the surface of parasites that are better at binding host cells. To interrogate a predicted function of this protein, we utilized bioinformatic protein prediction programs which allowed us to uncover the first cadherin-like protein (CLP) found in a parasite. Cadherin proteins are conserved metazoan proteins with central roles in cell-cell adhesion, development, and tissue structure maintenance. Functional characterization of this CLP from the unicellular parasite Trichomonas vaginalis demonstrated that the protein mediates both parasite-parasite and parasite-host adherence, which leads to an enhanced killing of host cells by T. vaginalis. Our findings demonstrate the presence of CLPs in unicellular pathogens and identify a new host cell binding protein family in a human-infective parasite.Yi-Pei ChenAngelica M. RiestraAnand Kumar RaiPatricia J. JohnsonAmerican Society for MicrobiologyarticleTrichomonas vaginalishost-pathogen interactionsparasite attachmentMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Trichomonas vaginalis host-pathogen interactions parasite attachment Microbiology QR1-502
spellingShingle	Trichomonas vaginalis host-pathogen interactions parasite attachment Microbiology QR1-502 Yi-Pei Chen Angelica M. Riestra Anand Kumar Rai Patricia J. Johnson A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
description	ABSTRACT Trichomonas vaginalis, a prevalent sexually transmitted parasite, adheres to and induces cytolysis of human mucosal epithelial cells. We have characterized a hypothetical protein, TVAG_393390, with predicted tertiary structure similar to that of mammalian cadherin proteins involved in cell-cell adherence. TVAG_393390, renamed cadherin-like protein (CLP), contains a calcium-binding site at a position conserved in cadherins. CLP is surface localized, and its mRNA and protein levels are significantly upregulated upon parasite adherence to host cells. To test the roles of CLP and its calcium-binding dependency during host cell adherence, we first demonstrated that wild-type CLP (CLP) binds calcium with a high affinity, whereas the calcium-binding site mutant protein (CLP-mut) does not. CLP and CLP-mut constructs were then used to overexpress these proteins in T. vaginalis. Parasites overexpressing CLP have ∼3.5-fold greater adherence to host cells than wild-type parasites, and this increased adherence is ablated by mutating the calcium-binding site. Additionally, competition with recombinant CLP decreased parasite binding to host cells. We also found that overexpression of CLP induced parasite aggregation which was further enhanced in the presence of calcium, whereas CLP-mut overexpression did not affect aggregation. Lastly, parasites overexpressing wild-type CLP induced killing of host cells ∼2.35-fold, whereas parasites overexpressing CLP-mut did not have this effect. These analyses describe the first parasitic CLP and demonstrate a role for this protein in mediating parasite-parasite and host-parasite interactions. T. vaginalis CLP may represent convergent evolution of a parasite protein that is functionally similar to the mammalian cell adhesion protein cadherin, which contributes to parasite pathogenesis. IMPORTANCE The adherence of pathogens to host cells is critical for colonization of the host and establishing infection. Here we identify a protein with no known function that is more abundant on the surface of parasites that are better at binding host cells. To interrogate a predicted function of this protein, we utilized bioinformatic protein prediction programs which allowed us to uncover the first cadherin-like protein (CLP) found in a parasite. Cadherin proteins are conserved metazoan proteins with central roles in cell-cell adhesion, development, and tissue structure maintenance. Functional characterization of this CLP from the unicellular parasite Trichomonas vaginalis demonstrated that the protein mediates both parasite-parasite and parasite-host adherence, which leads to an enhanced killing of host cells by T. vaginalis. Our findings demonstrate the presence of CLPs in unicellular pathogens and identify a new host cell binding protein family in a human-infective parasite.
format	article
author	Yi-Pei Chen Angelica M. Riestra Anand Kumar Rai Patricia J. Johnson
author_facet	Yi-Pei Chen Angelica M. Riestra Anand Kumar Rai Patricia J. Johnson
author_sort	Yi-Pei Chen
title	A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_short	A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_full	A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_fullStr	A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_full_unstemmed	A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>
title_sort	novel cadherin-like protein mediates adherence to and killing of host cells by the parasite <named-content content-type="genus-species">trichomonas vaginalis</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e008584119374662bdcc4571afe08afc
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A Novel Cadherin-like Protein Mediates Adherence to and Killing of Host Cells by the Parasite <named-content content-type="genus-species">Trichomonas vaginalis</named-content>

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