دورية أكاديمية
The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites.
| العنوان: | The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites. |
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| المؤلفون: | Silveira ACA; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Uombe NPI; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Velikkakam T; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Borges BC; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Teixeira TL; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil., de Almeida VF; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Torres JDA; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Pereira CL; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., de Souza G; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Teixeira SC; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Servato JPS; Faculdade de Odontologia, Universidade de Uberaba, Uberaba, Minas Gerais, Brazil., Silva MJB; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Mineo TWP; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Ribas RM; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil., Mortara RA; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil., da Silveira JF; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil., da Silva CV; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil. |
| المصدر: | Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2024 Jun 26; Vol. 14, pp. 1412345. Date of Electronic Publication: 2024 Jun 26 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101585359 Publication Model: eCollection Cited Medium: Internet ISSN: 2235-2988 (Electronic) Linking ISSN: 22352988 NLM ISO Abbreviation: Front Cell Infect Microbiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media SA |
| مواضيع طبية MeSH: | Trypanosoma cruzi*/genetics , Trypanosoma cruzi*/pathogenicity , Trypanosoma cruzi*/physiology , Trypanosoma cruzi*/metabolism , Chagas Disease*/parasitology , Mice, Inbred BALB C* , Protozoan Proteins*/genetics , Protozoan Proteins*/metabolism , Disease Models, Animal*, Animals ; Mice ; Cell Line ; Virulence ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Humans ; Host-Parasite Interactions ; Gene Knockout Techniques ; Parasitemia |
| مستخلص: | P21 is a protein secreted by all forms of Trypanosoma cruzi ( T. cruzi ) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21 -/- ) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21 -/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21 -/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21 -/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21 -/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Silveira, Uombe, Velikkakam, Borges, Teixeira, de Almeida, Torres, Pereira, de Souza, Teixeira, Servato, Silva, Mineo, Ribas, Mortara, da Silveira and da Silva.) |
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| فهرسة مساهمة: | Keywords: CRISPR/Cas9; Trypanosoma cruzi; cell invasion; intracellular multiplication; parasite-host interaction; virulence |
| المشرفين على المادة: | 0 (Protozoan Proteins) 0 (Cyclin-Dependent Kinase Inhibitor p21) |
| تواريخ الأحداث: | Date Created: 20240711 Date Completed: 20240711 Latest Revision: 20240712 |
| رمز التحديث: | 20240712 |
| مُعرف محوري في PubMed: | PMC11233463 |
| DOI: | 10.3389/fcimb.2024.1412345 |
| PMID: | 38988814 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2235-2988 |
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| DOI: | 10.3389/fcimb.2024.1412345 |