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A Novel Trichomonas vaginalis Surface Protein Modulates Parasite Attachment via Protein: Host Cell Proteoglycan Interaction

Molgora, Brenda M. and Rai, Anand Kumar and Sweredoski, Michael J. and Moradian, Annie and Hess, Sonja and Johnson, Patricia J. (2021) A Novel Trichomonas vaginalis Surface Protein Modulates Parasite Attachment via Protein: Host Cell Proteoglycan Interaction. mBio, 12 (1). Art. No. e03374-20. ISSN 2150-7511. PMCID PMC7885099. https://resolver.caltech.edu/CaltechAUTHORS:20210210-080709083

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Abstract

Trichomonas vaginalis is a highly prevalent, sexually transmitted parasite which adheres to mucosal epithelial cells to colonize the human urogenital tract. Despite adherence being crucial for this extracellular parasite to thrive within the host, relatively little is known about the mechanisms or key molecules involved in this process. Here, we have identified and characterized a T. vaginalis hypothetical protein, TVAG_157210 (TvAD1), as a surface protein that plays an integral role in parasite adherence to the host. Quantitative proteomics revealed TvAD1 to be ∼4-fold more abundant in parasites selected for increased adherence (MA parasites) than the isogenic parental (P) parasite line. De novo modeling suggested that TvAD1 binds N-acetylglucosamine (GlcNAc), a sugar comprising host glycosaminoglycans (GAGs). Adherence assays utilizing GAG-deficient cell lines determined that host GAGs, primarily heparan sulfate (HS), mediate adherence of MA parasites to host cells. TvAD1 knockout (KO) parasites, generated using CRISPR-Cas9, were found to be significantly reduced in host cell adherence, a phenotype that is rescued by overexpression of TvAD1 in KO parasites. In contrast, there was no significant difference in parasite adherence to GAG-deficient lines by KO parasites compared with wild-type, which is contrary to that observed for KO parasites overexpressing TvAD1. Isothermal titration calorimetric (ITC) analysis showed that TvAD1 binds to HS, indicating that TvAD1 mediates host cell adherence via HS interaction. In addition to characterizing the role of TvAD1 in parasite adherence, these studies reveal a role for host GAG molecules in T. vaginalis adherence.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1128/mbio.03374-20DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7885099/PubMed CentralArticle
ORCID:
AuthorORCID
Sweredoski, Michael J.0000-0003-0878-3831
Moradian, Annie0000-0002-0407-2031
Hess, Sonja0000-0002-5904-9816
Additional Information:© 2021 Molgora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Received 7 December 2020; Accepted 15 December 2020; Published 9 February 2021. We thank Jeffrey D. Esko for the CHO cell lines; Brian Janssen, Yi-Pei Chen, Katherine Muratore, and Fitz Gerald Diala for valuable discussions; Fernanda Santiago and Susan Lei for technical assistance; and Katherine Muratore and Shuqi Edward Wang for critical comments on the manuscript. This work was funded by NIH grants R01AI103182 and R33AI119721 to P.J.J. B.M.M. received support from NIH Ruth L. Kirschstein National Research Service awards AI007323 and GM00718 and a UCLA Eugene V. Cota-Robles fellowship.
Funders:
Funding AgencyGrant Number
NIHR01AI103182
NIHR33AI119721
NIHAI007323
NIHGM007185
UCLAUNSPECIFIED
Subject Keywords:Trichomonas vaginalis, adherence, proteomics, glycosaminoglycans, heparan sulfate, host-pathogen interactions
Issue or Number:1
PubMed Central ID:PMC7885099
Record Number:CaltechAUTHORS:20210210-080709083
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210210-080709083
Official Citation:Molgora BM, Rai AK, Sweredoski MJ, Moradian A, Hess S, Johnson PJ. 2021. A novel Trichomonas vaginalis surface protein modulates parasite attachment via protein: host cell proteoglycan interaction. mBio 12:e03374-20. https://doi.org/10.1128/mBio.03374-20
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107978
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Feb 2021 17:29
Last Modified:22 Feb 2021 21:02

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