Microarray based analysis of temperature and oxidative stress induced messenger RNA in Schistosoma mansoni

Abstract

The body's defense against schistosome infection can take many forms. For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and early oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host immune system. The most common treatment for schistosomiasis is the anti-helminthic drug praziquantel. Its effectiveness, however, is limited due to its inability to kill schistosomes 2 -4 weeks post-infection. Clearly there is a need for new antischistosomal drugs. We hypothesize that gene products expressed as part of a protective response against heat and/or oxidative stress are potential therapeutic targets for future drug development. Using a 12,166 element oligonucleotide microarray to characterize Schistosoma mansoni genes induced by heat and oxidative stress we found that 1,878 S. mansoni elements were significantly induced by heat stress. These included previously reported heat-shock genes expressing homologs of HSP40, HSP70 and HSP86. One thousand and one elements were induced by oxidative stress including those expressing homologs of superoxide dismutase, glutathione peroxidase and aldehyde dehydrogenase. Seventy-two elements were common to both stressors and could potentially be exploited in the development of novel anti-schistosomal therapeutics.

Better Understanding of Anti-Schistosomal Strategies Through Microarray Analysis

“…The study included in vitro assays of adult S. mansoni exposed to praziquantel, with subsequent microarray analysis identifying 726 up-regulated and 347 down-regulated genes. The results correlated with known oxidative-stress genes such extracellular superoxide dismutase precursor, glycerol-3-phosphate dehydrogenase, isocitrate dehydrogenase, cytochrome c oxidase subunit 2, and thioredoxin peroxidise which were all previous reported for S. mansoni [39]. Surprisingly the 1 and 3 hour in vitro exposure to praziquantel didn't modulate the expression of previously reported anti-detoxification genes including superoxide dismutase, glutathione peroxidase or glutathione transferase, a fact the authors suggest may be due to the relatively low levels of drug that was used in the study.…”

“…For example, the use of longer time courses or contrasting treatment regimes could have helped to differentiate between direct, indirect and secondary effects [40]. The use of a generalised stressor in a previous microarray study by the same group produced a large list of differential genes [39], These oxidative and temperature stress response genes of adult S. mansoni parasites [39], when compared to the praziquantel dataset produced a large overlap, indicative of indirect or secondary effects of the drug treatment. Finally, in vivo effects of praziquantel will be significantly different due to the combination of chemotherapeutic and host immunological effects on the parasite [41,42], and as such the reported in vitro assays presented here may not present the whole picture.…”

Therapeutic Effects of Allium sativum and Allium cepa in Schistosoma mansoni experimental infection

“…For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host immune system which is counteracted by the parasite antioxidant defense mechanism (ARAGON et al 2008). Due to the lack of a vaccine, patient therapy is heavily reliant on chemotherapy with praziquantel as the World Health Organization-recommended drug, but concerns over drug resistance and possible reoccurrence of infection encouraged the search for new drug leads, possibly from natural resources (ABDULLA et al 2007;ABEBE, 2008).…”

The potential role of mefloquine against Schistosoma mansoni infection by prohibition of hepatic oxidative stress in mice

“…As the infection becomes established, the parasite comes under oxidative stress generated by the host immune system which is counteracted by the parasite antioxidant defense mechanism (Aragon et al, 2008). The generation of oxygen-derived free radicals may be an initial, nonspecific defense reaction of the host toward parasitic infection.…”