Suppressing Glucose Transporter Gene Expression in Schistosomes Impairs Parasite Feeding and Decreases Survival in the Mammalian Host

PLoS Pathogens

Charles B. Shoemaker¹  Guilherme Oliveira²  Mariana Simoes²  Patrick J. Skelly³  Zahra Faghiri³  David Ndegwa³  Greice Krautz-Peterson³ 

[1] Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, BA, Brazil;Laboratory of Cellular and Molecular Parasitology and CEBio, Instituto René Rachou - FIOCRUZ, Belo Horizonte, MG, Brazil;Molecular Helminthology Laboratory, Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University, Cummings School of Veterinary Medicine, Grafton, Massachusetts, United States of America

关键词: Glucose;    Parasitic diseases;    Small interfering RNAs;    Schistosoma;    RNA interference;    Gene expression;    Membrane proteins;    Double str;    ed RNA;   

DOI  :  10.1371/journal.ppat.1000932

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Adult schistosomes live in the host's bloodstream where they import nutrients such as glucose across their body surface (the tegument). The parasite tegument is an unusual structure since it is enclosed not by the typical one but by two closely apposed lipid bilayers. Within the tegument two glucose importing proteins have been identified; these are schistosome glucose transporter (SGTP) 1 and 4. SGTP4 is present in the host interactive, apical tegumental membranes, while SGTP1 is found in the tegumental basal membrane (as well as in internal tissues). The SGTPs act by facilitated diffusion. To examine the importance of these proteins for the parasites, RNAi was employed to knock down expression of both SGTP genes in the schistosomula and adult worm life stages. Both qRT-PCR and western blotting analysis confirmed successful gene suppression. It was found that SGTP1 or SGTP4-suppressed parasites exhibit an impaired ability to import glucose compared to control worms. In addition, parasites with both SGTP1 and SGTP4 simultaneously suppressed showed a further reduction in capacity to import glucose compared to parasites with a single suppressed SGTP gene. Despite this debility, all suppressed parasites exhibited no phenotypic distinction compared to controls when cultured in rich medium. Following prolonged incubation in glucose-depleted medium however, significantly fewer SGTP-suppressed parasites survived. Finally, SGTP-suppressed parasites showed decreased viability in vivo following infection of experimental animals. These findings provide direct evidence for the importance of SGTP1 and SGTP4 for schistosomes in importing exogenous glucose and show that these proteins are important for normal parasite development in the mammalian host.

【 授权许可】

CC BY