A mating-induced reproductive gene promotes Anopheles tolerance to Plasmodium falciparum infection

Perrine Marcenac, W. Robert Shaw, Evdoxia G. Kakani, Sara N. Mitchell, Adam South, Kristine Werling, Eryney Marrogi, Daniel G. Abernathy, Rakiswendé Serge Yerbanga, Roch K. Dabiré, Abdoulaye Diabaté, Thierry Lefèvre, Flaminia Catteruccia

Preprint posted on August 21, 2020

Article now published in PLOS Pathogens at

On the benefits of mating: relationships between Anopheles and Plasmodium

Selected by Mariana De Niz

Categories: cell biology, microbiology


Plasmodium transmission occurs via the infectious bite of mosquitoes of the Anopheles genus, which comprises three major subgenera: Cellia, present in Africa, the Indian sub-continent, South East Asia and Oceania; Nyssorhynchus, predominant in Central and South America, and Anopheles, which displays a wide distribution from North America to Asia. Given their long-term association with P. falciparum, an outstanding question is whether these vectors suffer fitness costs upon infection, including for instance, reduced longevity or impaired reproductive output. Previous work has suggested a discrepancy between findings in mosquitoes infected with the human-infective P. falciparum (suggesting no effect on longevity), and the rodent-infective Plasmodium berghei (suggesting reduced lifespan in females, and reduced ability to develop eggs).

In their work, Marcenac et al (1) address whether P. falciparum induces reproductive costs in Anopheles gambiae – the predominant Cellia vector in Sub-Saharan Africa. Moreover, the authors explore the mating-induced factors critical to maintaining mosquito tolerance to Plasmodium infection.

Key findings and developments

Reproductive fitness of An. gambiae and An. stephensi is not affected by P. falciparum infection. Equally, mating does not affect P. falciparum infection prevalence or infection intensity.

The authors began by analyzing the effects of infection and mating on egg development in An. gambiae and An. stephensi females. They found that virgin and mated females produced the same number of eggs, regardless of whether the bloodmeal they fed on, was infectious or not. Moreover, they found reproductive species-specific differences: the number of eggs developed in An. gambiae mated females was similar to virgins, while in An. stephensi, mating seemed to increase both, the likelihood of egg development, and the number of eggs developed.

Next, the authors analysed whether mating affects laboratory P. falciparum infections in An. gambiae and An. stephensi. Prevalence and intensity of infection were determined by counting midgut oocysts 7 days post-feeding with an infected bloodmeal. The authors determined that mating status did not affect either infection prevalence (proportion of mosquitoes infected), nor infection intensity (number of oocysts) in either of the mosquito species studied.

In the face of high intensity P. falciparum infections, MISO helps preserve reproductive fitness without affecting parasite survival

The authors had previously shown that in virgin An. gambiae, the steroid hormone 20E produced by females after blood feeding regulates the positive interaction between parasite and egg numbers. In the present work, Marcenac et al went on to investigate whether mating-induced processes regulated by sexual transfer of 20E might be important for the relationship between egg development and P. falciparum development in mated females. To investigate this, the authors performed infections in An. coluzzii mosquitoes from Burkina Faso with silenced MISO -a female reproductive gene induced by the male 20E, which influences lipid accumulation during egg development. Gametocytemia alone had no effect on the number of eggs developed by the control females; however, females with silenced MISO produced significantly fewer eggs at high gametocytemia infections relative to lower gametocytemia infections. This suggests that highly infectious P. falciparum bloodmeals reduce the reproductive fitness of females if the 20E-induced reproductive gene is depleted.

While oogenesis seemed to be affected, no differences were found in terms of infection prevalence or infection intensity in MISO-silenced females compared to controls, demonstrating that this gene does not impact parasite development. Additionally, the authors found that while control female mosquitoes had a higher chance of developing eggs as the oocyst burden increased, MISO-silenced females had a significantly reduced probability of egg development at increasingly high parasite loads.

What I like about this preprint

I liked this preprint because it adds an important piece of information to our growing knowledge on Plasmodium transmission in malaria-endemic areas. The work is very clear, and opens various potential avenues for research.



  1. Marcenac P, et al A mating-induced reproductive gene promotes Anopheles tolerance to Plasmodium falciparum infection, bioRxiv, 2020.


Posted on: 7th December 2020


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Author's response

Perrine Marcenac and Flaminia Catteruccia shared

Open questions  

1.You mention in your work that conflicting results have been found upon comparing effects on mosquito fitness upon infections with falciparum or P. berghei. What do you attribute these differences to? For instance, were these comparable laboratory infections, or infections in the wild? Do rodent Plasmodium species in general tend to show similar effects on mosquito fitness, or is this something specific to P. berghei? If so, what is this possibly attributed to?

Results showing that Plasmodium induces fitness costs in mosquitoes often used non-natural vector-parasite associations. An. gambiae, An. coluzzii, and An. stephensi do not naturally transmit mouse malarias, including P. berghei, P. yoelii nigeriensis, and P. chabaudi, whereas these species are natural vectors of P. falciparum parasites. We and others have hypothesized that Anopheles mosquitoes do not suffer fitness costs when they are infected with parasites that they naturally transmit in the wild because they have evolved molecular mechanisms to limit possible costs of infections after millions of years of co-evolution with these parasites and their ancestral forms.

2.Plasmodium berghei is generally associated with much higher parasite intensity in mosquitoes. How does this relate to your findings regarding MISO and 20E?

It is difficult to relate high-intensity, P. berghei infections from experimental models to our results with MISO and 20E, as we sought to examine mosquito fitness in natural vector-parasite interactions. We believe the relationship between MISO and fitness in the face of P. falciparum infection is likely to differ in the case of P. berghei infection, as vectors of the Cellia subgenera have co-evolved with P. falciparum and its ancestral species for millions of years, while this is not the case with P. berghei.

3.How does the division of the mosquito populations across sub-genera and different world regions affect their ability to transmit P. falciparum with or without an effect on fitness?

Our studies used a combination of natural P. falciparum isolates from Burkina Faso and a P. falciparum strain that comes from sub-Saharan African (NF54). An. gambiae and An. coluzzii are natural vectors of sub-Saharan isolates of P. falciparum, and in these infections we did not see a cost to fecundity associated with infection. While this is not something we examined in our study, it is possible that the evolution of molecular mechanisms to minimize fitness costs to infection may also be dependent on the geographic origin of the P. falciparum isolate. For example, Anopheles albimanus of the Nyssorhynchus subgenus in South America, or Anopheles atroparvus of the Anopheles subgenus in Europe, may have fitness costs associated with isolates of P. falciparum from sub-Saharan Africa but not with isolates from their region.

4.Additional to your work on mating-induced reproductive genes, do you think other factors link P.  falciparum prevalence/intensity, and fitness? For instance, do you think mosquito microbiota is relevant? Or other factors, and if so, which ones?

Previous work from our lab has shown that genes related to 20E signaling and egg development after blood feeding are important for the relationship between parasite and egg development (Werling, Shaw, Itoe et al. Cell 2019). As the mosquito midgut microbiome changes after blood feeding and has been previously shown to be important for parasite development, it is also possible it could impact the relationship between parasite and egg development.


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