First insights into the autophagy machinery of adult Schistosoma mansoni. Issue 7 (June 2021)

• Record Type: Journal Article
• Authors: Mughal, Mudassar N.; Grevelding, Christoph G.; Haeberlein, Simone
• Is Part Of: International journal for parasitology. Volume 51:Issue 7(2021)
• Page Start: 571
• Page End: 585
• Publication Date: 2021-06
• Subjects: Schistosoma mansoni -- Autophagy -- Reproduction -- Inhibitors -- DAP1 -- LC3B; Parasitology -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; Parasitology; Periodicals; Electronic journals; 571.999
• DOI: 10.1016/j.ijpara.2020.11.011
• Languages: English
• ISSNs: 0020-7519

Abstract

Graphical abstract: Highlights: Several key autophagy genes were identified in Schistosoma mansoni, including Beclin and LC3. Dram and Dap1 showed a sex-dependent expression in male versus female worms. Dap1 transcript levels were influenced by in vitro culture conditions in female worms. Treatment with autophagy inhibitors affected parasite vitality and gonadal tissues. A search for anti-schistosomal targets within the autophagy machinery is promising. Abstract: Schistosomiasis is a disease of global importance caused by parasitic flatworms, schistosomes, which cause pathogenicity through eggs laid by the female worm inside the host's blood vessels. Maintenance of cellular homeostasis is crucial for parasites, as for other organisms, and is quite likely important for schistosome reproduction and vitality. We hypothesize a role for autophagy in these processes, an evolutionarily conserved and essential cellular degradation pathway. Here, for the first known time, we shed light on the autophagy machinery and its involvement in pairing-dependent processes, vitality and reproduction of Schistosoma mansoni . We identified autophagy genes by in silico analyses and determined the influence of in vitro culture on the transcriptional expression in male and female worms using quantitative real-time PCR. Among the identified autophagy genes were Beclin, Ambra1, Vps34, DRAM, DAP1, and LC3B, of which some showed a sex-dependent expression. Specifically, the death-associated protein DAP1 was significantly more highly expressed in females compared with males, while for the damage-regulated autophagy modulator DRAM it was the opposite. Furthermore, in-vitro culture significantly changed the transcript expression level of DAP1 in female worms. Next, worms were treated with an autophagy inducer (rapamycin) or inhibitors (bafilomycin A1, wortmannin and spautin-1) to evaluate effects on autophagy protein expression, worm vitality, and reproduction. The conversion of the key autophagy protein LC3B, a marker for autophagic activity, was increased by rapamycin and blocked by bafilomycin. All inhibitors affected worm fitness, egg production, and negatively affected the morphology of gonads and intestine. In summary, autophagy genes in S. mansoni show an interesting sex-dependent expression pattern and manipulation of autophagy in S. mansoni by inhibitors induced detrimental effects, which encourages subsequent studies to identify antischistosomal targets within the autophagy machinery.