Killer yeasts exert anti-plasmodial activities against the malaria parasite Plasmodium berghei in the vector mosquito Anopheles stephensi and in mice

Abstract

Background Wickerhamomyces anomalus is a yeast associated with different insects including mosquitoes, where it is proposed to be involved in symbiotic relationships with hosts. Different symbiotic strains of W. anomalus display a killer phenotype mediated by protein toxins with broad-spectrum antimicrobial activities. In particular, a killer toxin purified from a W. anomalus strain ( Wa F17.12), previously isolated from the malaria vector mosquito Anopheles stephensi , has shown strong in vitro anti-plasmodial activity against early sporogonic stages of the murine malaria parasite Plasmodium berghei . Results Here, we provide evidence that Wa F17.12 cultures, properly stimulated to induce the expression of the killer toxin, can directly affect in vitro P. berghei early sporogonic stages, causing membrane damage and parasite death. Moreover, we demonstrated by in vivo studies that mosquito dietary supplementation with activated Wa F17.12 cells interfere with ookinete development in the midgut of An. stephensi . Besides the anti-sporogonic action of Wa F17.12, an inhibitory effect of purified Wa F17.12-killer toxin was observed on erythrocytic stages of P. berghei , with a consequent reduction of parasitaemia in mice. The preliminary safety tests on murine cell lines showed no side effects. Conclusions Our findings demonstrate the anti-plasmodial activity of Wa F17.12 against different developmental stages of P. berghei . New studies on P. falciparum are needed to evaluate the use of killer yeasts as innovative tools in the symbiotic control of malaria. Electronic supplementary material The online version of this article (10.1186/s13071-019-3587-4) contains supplementary material, which is available to authorized users.

Mosquito Mycobiota: An Overview of Non-Entomopathogenic Fungal Interactions

“…Parasite death is induced by the hydrolysis of the β-glucans located in cell-wall membranes of parasites. It was shown that yeasts could reduce the number of parasites (zygotes and ookinetes) by 65% [57]. Contrary to the observations made in vitro [56], no parasitic effect has been shown in vivo on oocysts and sporozoites.…”

“…This killing mechanism, which could protect Anopheles mosquitoes from infection by entomopathogenic fungi, is partly based on an exo-β-1,3-glucanase enzymatic activity of the toxins [56]. Due to their presence in the midgut and the exo-β-1,3-glucanase enzymatic activity of their toxins, these W. anomalus strains strongly inhibit the development of Plasmodium berghei from gametocytes to ookinetes in females [57]. Parasite death is induced by the hydrolysis of the β-glucans located in cell-wall membranes of parasites.…”

“…Contrary to the observations made in vitro [56], no parasitic effect has been shown in vivo on oocysts and sporozoites. This lack of effect could be explained by the fact that these two stages of the sporogonic phase are located outside the lumen of the midgut and therefore never come into contact with yeast toxins [57].…”

Gut microbiota is essential in PGRP-LA regulated immune protection against Plasmodium berghei infection

“…Oral administration of live or heat-inactivated bacteria isolated from mosquito midgut significantly decreases the infection rate of P. falciparum [20]. Wickerhamomyces anomalus, a yeast involved in symbiotic relationships with Anopheles, is able to directly eliminate Plasmodium through secreting killer toxin [21,22]. Another stably inherited gut commensal bacteria, Asaia, can be genetically modified and directly inhibits pathogen development by secreting antiplasmodial effectors [23].…”

Vector-focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies

“…The symbiotic yeast Wickerhamomyces anomalus strain (WaF17.12), isolated from the malaria vector mosquito Anopheles stephensi, has shown strong in-vitro anti-plasmodial activity. Mosquitoes colonized with WaF17.12 developed 65.2% fewer parasites than the control group [181]. More recently, a symbiont microsporidian (Microsporidia MB ) that colonizes An.…”