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Lefevre, T.

Publications and source records attributed to Lefevre, T..

3 recordsLinked to original sources

Chromatin changes induced by a Plasmodium falciparum infection in Anopheles gambiae

Infection by the human malaria parasite leads to important changes in mosquito phenotypic traits related to vector competence. However, we still lack a clear understanding of the underlying mechanisms and in particular, of the epigenetic basis for these changes. We have examined genome-wide distribution maps of H3K27ac, H3K9ac, H3K9me3 and H3K4me3 by ChIP-seq and the transcriptome by RNA-seq, of midguts from Anopheles gambiae mosquitoes infected with natural isolates of the human malaria parasite Plasmodium falciparum in Burkina Faso. We report 15,916 regions containing differential histone modification enrichment, of which 8,339 locate at promoters and/or intersect with genes. The functional annotation of these regions allowed us to identify infection responsive genes showing differential enrichment in various histone modifications, such as CLIP pro-teases, anti-microbial peptides encoding genes, and genes related to melanization responses and the complement system. Further, the motif analysis of regions differentially enriched in various histone modifications predicts binding sites that might be involved in the cis-regulation of these regions such as Deaf1, Pangolin and Dorsal transcription factors (TFs). Some of these TFs are known to regulate immunity gene expression in Drosophila and are involved in the Notch and JAK/STAT signaling pathways. The analysis of malaria infection-induced chromatin changes in mosquitoes is important not only to identify regulatory elements and genes underlying mosquito responses to a P. falciparum infection but also for possible applications to the genetic manipulation of mosquitoes and to other mosquito-borne systems.

molecular biology

Field evidence for manipulation of mosquito host selection by the human malaria parasite, Plasmodium falciparum

Whether the malaria parasite Plasmodium falciparum can manipulate mosquito host choice in ways that enhance parasite transmission toward humans is unknown. We assessed the influence of P. falciparum on the blood-feeding behaviour of three of its major vectors (Anopheles coluzzii, An. gambiae and An. arabiensis) in Burkina Faso. Host preference assays using odour-baited traps revealed no effect of infection on mosquito long-range anthropophily. However, the identification of the blood meal origin of mosquitoes showed that females carrying sporozoites, the mature transmissible stage of the parasite, displayed a 24% increase in anthropophagy compared to both females harbouring oocysts, the parasite immature stage, and uninfected individuals. Using a mathematical model, we further showed that this increased anthropophagy in infectious females resulted in a > 250% increase in parasite transmission potential, everything else being equal. This important epidemiological consequence highlights the importance of vector control tools targeting infectious females.

evolutionary biology

Can malaria parasites manipulate the odour-mediated host preference of their mosquito vectors?

Malaria parasites can manipulate mosquito feeding behaviours such as motivation and avidity to feed on vertebrate hosts in ways that increase parasite transmission. However, in natural conditions, not all vertebrate blood-sources are suitable hosts for the parasite. Whether malaria parasites can manipulate mosquito host choice in ways that enhance parasite transmission toward suitable hosts and/or reduce mosquito attraction to unsuitable hosts (i.e. specific manipulation) is unknown. To address this question, we experimentally infected three species of mosquito vectors (Anopheles coluzzii, Anopheles gambiae, and Anopheles arabiensis) with wild isolates of the human malaria parasite Plasmodium falciparum, and examined the effects of immature (oocyst) and mature (sporozoite) infections on mosquito behavioural responses (activation rate and odour choice) to combinations of calf odour, human odour and outdoor air using a dual-port olfactometer. Regardless of parasite developmental stage and mosquito species, P. falciparum infection did not alter mosquito activation rate or their choice for human odours. The overall expression pattern of host choice of all three mosquito species was consistent with a high degree of anthropophily, with both infected and uninfected individuals showing higher attraction toward human odour over calf odour, human odour over outdoor air, and outdoor air over calf odour. Our results suggests that, in this system, the parasite may not be able to manipulate the early long-range behavioural steps involved in the mosquito host-feeding process, including initiation of host-seeking and host orientation. Future studies examining mosquito host-feeding behaviours at a shorter range (i.e. the \"at-host\" foraging activities) are required to test whether malaria parasites can modify their mosquito host choice to enhance transmission toward suitable hosts and/or reduce biting on unsuitable hosts.

evolutionary biology