دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: A Novel Trichomonas vaginalis Surface Protein Modulates Parasite Attachment via Protein:Host Cell Proteoglycan Interaction.
المؤلفون: Molgora BM; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.; Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA., Rai AK; Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA., Sweredoski MJ; Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, California, USA., Moradian A; Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, California, USA., Hess S; Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, California, USA., Johnson PJ; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA johnsonp@ucla.edu.; Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA.
المصدر: MBio [mBio] 2021 Feb 09; Vol. 12 (1). Date of Electronic Publication: 2021 Feb 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Cell Adhesion* , Host-Parasite Interactions*, Proteoglycans/*metabolism , Protozoan Proteins/*genetics , Trichomonas vaginalis/*chemistry , Trichomonas vaginalis/*physiology, Animals ; CHO Cells ; Cell Line ; Computational Biology ; Cricetulus ; Epithelial Cells/parasitology ; Proteomics ; Protozoan Proteins/metabolism ; Trichomonas vaginalis/genetics
مستخلص: 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. IMPORTANCE The ability of the sexually transmitted parasite Trichomonas vaginalis to adhere to its human host is critical for establishing and maintaining an infection. Yet how parasites adhere to host cells is poorly understood. In this study, we employed a novel adherence selection method to identify proteins involved in parasite adherence to the host. This method led to the identification of a protein, with no previously known function, that is more abundant in parasites with increased capacity to bind host cells. Bioinformatic modeling and biochemical analyses revealed that this protein binds a common component on the host cell surface proteoglycans. Subsequent creation of parasites that lack this protein directly demonstrated that the protein mediates parasite adherence via an interaction with host cell proteoglycans. These findings both demonstrate a role for this protein in T. vaginalis adherence to the host and shed light on host cell molecules that participate in parasite colonization.
(Copyright © 2021 Molgora et al.)
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معلومات مُعتمدة: R01 AI103182 United States AI NIAID NIH HHS; R33 AI119721 United States AI NIAID NIH HHS; T32 AI007323 United States AI NIAID NIH HHS; T32 GM007185 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Trichomonas vaginalis; adherence; glycosaminoglycans; heparan sulfate; host-pathogen interactions; proteomics
المشرفين على المادة: 0 (Proteoglycans)
0 (Protozoan Proteins)
تواريخ الأحداث: Date Created: 20210210 Date Completed: 20210826 Latest Revision: 20240330
رمز التحديث: 20240330
مُعرف محوري في PubMed: PMC7885099
DOI: 10.1128/mBio.03374-20
PMID: 33563826
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mBio.03374-20