Steroid Hormone Function Controls Non-competitive Plasmodium Development in Anopheles

Abstract

Graphical AbstractHighlights d Human malaria parasites interact non-competitively with their mosquito vectors d Mosquito hormone signaling co-regulates egg and parasite development d Parasites use host lipids for their growth via a mosquito lipid transporter d Parasites respond to mosquito metabolism with consequences for vector controlThe development of the malaria-causing parasite Plasmodium falciparum depends on its ability to exploit the sexual cycle of its mosquito host in a noncompetitive manner. SUMMARYTransmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20hydroxyecdysone (20E), remains largely unknown.Here we show that Plasmodium falciparum development is intimately but not competitively linked to processes shaping Anopheles gambiae reproduction. We unveil a 20E-mediated positive correlation between egg and oocyst numbers; impairing oogenesis by multiple 20E manipulations decreases parasite intensities. These manipulations, however, accelerate Plasmodium growth rates, allowing sporozoites to become infectious sooner. Parasites exploit mosquito lipids for faster growth, but they do so without further affecting egg development. These results suggest that P. falciparum has adopted a non-competitive evolutionary strategy of resource exploitation to optimize transmission while minimizing fitness costs to its mosquito vector. Our findings have profound implications for currently proposed control strategies aimed at suppressing mosquito populations.

Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals

“…While an additional feeding does not limit human malaria parasite numbers unlike their rodent malaria counterparts (Figures 1 and 3), when evaluating oocyst numbers we noticed stark differences in parasite growth between Plasmodium species in the surviving oocysts (Figure 4). P. falciparum oocysts are significantly larger when mosquitoes receive an additional blood- or protein-meal when compared to mosquitoes maintained on sucrose alone after the infectious bloodmeal (Figure 4A), arguing that human malaria parasites are able to utilize host resources to accelerate their growth as previously suggested (Costa et al, 2018; Werling et al, 2019). Differences in oocyst size between blood- or protein-meal were not significant (Figure 4A).…”

“…While no differences in P. berghei oocyst size were detected, P. falciparum oocysts significantly increased following additional feeding, suggesting that human malaria parasites utilize the added resources provided in a blood- or protein-meal to increase their growth. Previous work argues that the increase in lipid resources that accompany feeding are utilized by the developing oocyst for growth and sporozoite production (Costa et al, 2018; Werling et al, 2019). Moreover, an additional feeding increases the number of P. falciparum salivary gland sporozoites (Ponnudurai et al, 1989; Rosenberg and Rungsiwongse, 1991), arguing that this increased growth may enhance the potential for malaria transmission.…”

JNK signaling regulates oviposition in the malaria vectorAnopheles gambiae

“…In addition, given the importance of the JNK pathway in the An. gambiae immune response to some Plasmodium infections (Garver et al, 2013; Ramphul et al, 2015) and the centrality of 20E to mosquito physiology and parasite development (Werling et al, 2019), it will be informative to examine whether 20E signaling in other contexts (e.g. after blood feeding) also engages with the JNK pathway.…”

Exposure of Anopheles mosquitoes to trypanosomes reduces reproductive fitness and enhances susceptibility to Plasmodium

“…Vg expression decreased significantly in mosquitoes exposed to trypanosomes but was not modified by another eukaryotic microorganism, such as P. yoelii, when it was ingested alone ( Fig 3A). To strengthen this finding, we also tested the expression of another lipid transporter, the Lipophorin (Lp), another yolk protein precursor in mosquitoes [45,46], and also controlled via the 20E pathway [44]. We observed that, as for Vg expression, Lp expression is decreased 48h post trypanosome ingestion (S2A Fig).…”

“…Mosquito egg maturation induces the expression of the gene encoding for the precursor of the major yolk protein, vitellogenin (Vg) through the activation of the 20-hydroxyecdysone (20E) pathway [42][43][44]. In order to measure the effect of trypanosome ingestion on mosquito reproductive fitness, we measured expression of Vg 48h after feeding on blood with or without trypanosomes.…”