Non-competitive resource exploitation within mosquito shapes within-host malaria infectivity and virulence

Abstract

Malaria is a fatal human parasitic disease transmitted by a mosquito vector. Although the evolution of within-host malaria virulence has been the focus of many theoretical and empirical studies, the vector’s contribution to this process is not well understood. Here, we explore how within-vector resource exploitation would impact the evolution of within-host Plasmodium virulence. By combining within-vector dynamics and malaria epidemiology, we develop a mathematical model, which predicts that non-competitive parasitic resource exploitation within-vector restricts within-host parasite virulence. To validate our model, we experimentally manipulate mosquito lipid trafficking and gauge within-vector parasite development and within-host infectivity and virulence. We find that mosquito-derived lipids determine within-host parasite virulence by shaping development (quantity) and metabolic activity (quality) of transmissible sporozoites. Our findings uncover the potential impact of within-vector environment and vector control strategies on the evolution of malaria virulence.

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.…”

Plasmodiumoocysts respond with dormancy to crowding and nutritional stress

“…To date, mostly indirect evidence exists for a Plasmodium oocyst strategy to cope with nutritional stress. P. berghei oocyst size and sporozoite output are markedly reduced in Anopheles gambiae silenced for Lipophorin (Lp), the main lipid transporter of insects 4,16 , and as mentioned previously very high P. berghei infections result in reduced number of sporozoites in A. stephensi salivary glands 8 . These reports and unpublished observations we and others have made over the years led us to hypothesize that experimental infections may cause a nutritional stress to the developing oocyst, affecting sporogonic development and the measurable infection outcome.…”

“…The negative density-dependent effect on the oocyst is exacerbated in standard laboratory infections where infected mosquitoes are often not provided supplemental bloodmeals, leading to acute depletion of nutrient reserves 4–7,26 . In nature, a female mosquito acquires a bloodmeal every 2-3 days 27,28 , which helps it meet the high energy and nutrient demand for flight and reproduction.…”

“…Experimental mosquito infections with Plasmodium parasites, and microscopic enumeration of oocysts is the gold standard for evaluation of transmission reduction, whereby mosquitoes are offered an infectious bloodmeal and maintained on sugar solution until oocysts are counted 3 . Infections often lead to high oocyst loads and consequently massive proliferation of sporozoites, causing depletion of nutrients in the vector 4–7 . For example, ultra-high intensity infections of Anopheles stephensi mosquitoes with the rodent parasite P. berghei leads to reduced number of sporozoites reaching the salivary glands and high mosquito mortality compared with lower infection intensities 8 .…”