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Cryptosporidium parvum Subtilisin-Like Serine Protease (SUB1) Is Crucial for Parasite Egress from Host Cells.
Nava, Samantha; White, A Clinton; Castellanos-González, Alejandro.
Affiliation
  • Nava S; Infectious Diseases Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
  • White AC; Infectious Diseases Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA acwhite@utmb.edu.
  • Castellanos-González A; Infectious Diseases Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Infect Immun ; 87(5)2019 03.
Article in En | MEDLINE | ID: mdl-30782859
ABSTRACT
Despite the severity and global burden of Cryptosporidium infection, treatments are less than optimal, and there is no effective vaccine. Egress from host cells is a key process for the completion of the life cycle of apicomplexan parasites. For Plasmodium species, subtilisin-like serine protease (SUB1) is a key mediator of egress. For Toxoplasma species, calcium-dependent protein kinases (CDPKs) are critical. In this study, we characterized Cryptosporidium SUB1 expression and evaluated its effect using an infection model. We found increased expression between 12 and 20 h after in vitro infection, prior to egress. We induced silencing of SUB1 (ΔSUB1) mRNA using SUB1 single-stranded antisense RNA coupled with human Argonaute 2. Silencing of SUB1 mRNA expression did not affect parasite viability, excystation, or invasion of target cells. However, knockdown led to a 95% decrease in the proportion of released merozoites in vitro (P < 0.0001). In contrast, silencing of CDPK5 had no effect on egress. Overall, our results indicate that SUB1 is a key mediator of Cryptosporidium egress and suggest that interruption of the life cycle at this stage may effectively inhibit the propagation of infection.
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Full text: 1 Database: MEDLINE Main subject: Oocytes / Subtilisins / Cryptosporidium parvum / Cryptosporidiosis / Host-Parasite Interactions Limits: Humans Language: En Journal: Infect Immun Year: 2019 Type: Article Affiliation country: United States

Full text: 1 Database: MEDLINE Main subject: Oocytes / Subtilisins / Cryptosporidium parvum / Cryptosporidiosis / Host-Parasite Interactions Limits: Humans Language: En Journal: Infect Immun Year: 2019 Type: Article Affiliation country: United States