Biology subjects

Lefevre, T.

Publications and source records attributed to Lefevre, T..

18 recordsLinked to original sources

bioRxiv2026

MaRNAV-1 infection of Plasmodium vivax is associated with increased parasite transmission and host inflammatory responses

MaRNAV-1 is an RNA virus recently identified in Plasmodium vivax-infected samples, but definitive evidence that it infects the parasite and influences malaria pathogenesis remains unknown. Here, we demonstrate that MaRNAV-1 is an intracellular virus that is present in P. vivax at various stages of its life cycle, including blood, sporozoite, and liver stages. Viral prevalence varied geographically between Cambodian and Ethiopian parasites. MaRNAV-1 presence and load were positively associated with parasite transmission potential, as reflected by increased gametocyte abundance and higher oocyst prevalence and intensity in membrane feeding assays. MaRNAV-1 loads were higher in symptomatic compared to asymptomatic infections, and higher MaRNAV-1 loads were associated with elevated body temperature, independently of parasitemia. MaRNAV-1 infection elicits an antibody response and is associated with dendritic cell activation, a shift from Th2 to a Th1-driven immune response, and an increased frequency of double-negative B cells. Accordingly, MaRNAV-1-infected patients had higher concentrations of circulating cytokines, such as IFN-{gamma}, CXCL10, IL-1RA, and IL-6, independently of parasitemia. Together, these findings demonstrate that MaRNAV-1 is a genuine parasite-infecting virus associated with increased parasite transmission potential and with modulation of clinical outcomes in, and host immune response to, P. vivax infections. Our study broadens the conventional view of host-pathogen interactions in malaria by revealing complex virus-parasite-host relationships.

microbiology↗

bioRxiv2025

Systematic evaluation of single-cell multimodal data integration for comprehensive human reference atlas.

The integration of multimodal single-cell data enables comprehensive organ reference atlases, yet its impact remains largely unexplored, particularly in complex tissues. We generated a benchmarking dataset for the renal cortex by integrating 3 and 5 scRNA-seq with joint snRNA-seq and snATAC-seq, profiling 119,744 high-quality nuclei/cells from 19 donors. To align cell identities and enable consistent comparisons, we developed the interpretable machine learning tool scOMM (single-cell Omics Multimodal Mapping) and systematically assessed integration strategies. "Horizontal" integration of scRNA and snRNA-seq improved cell-type identification, while "vertical" integration of snRNA-seq and snATAC-seq had an additive effect, enhancing resolution in homogeneous populations and difficult-to-identify states. Global integration was especially effective in identifying adaptive states and rare cell types, including WFDC2-expressing Thick Ascending Limb and Norn cells, previously undetected in kidney atlases. Our work establishes a robust framework for multimodal reference atlas generation, advancing single-cell analysis and extending its applicability to diverse tissues.

genomics↗

bioRxiv2024

Evidences that host genetic background more than the environment shapes the microbiota of the snail Bulinus truncatus, an intermediate host of Schistosoma species.

Microbiota are increasingly recognized as key players in regulating host biological functions, influencing both the ecology and evolution of organisms. However, the factors shaping microbiota diversity and structure in natural environments remain underexplored, especially the relative importance of host genetics versus environmental factors. In this study, we address this gap using the freshwater snail Bulinus truncatus, an intermediate host for some human and animal Schistosoma parasites, as a model species. We developed 31 new microsatellite markers to assess the population structure of B. truncatus across 9 sites in Senegal. We then applied metabarcoding to characterize the diversity and structure of individual snail bacterial microbiota and environmental communities associated with each sampling site using environmental DNA. We also used molecular diagnostics to determine trematode infection status of B. truncatus individuals. By integrating these data through multiple regression on distance matrices (MRM) analyses, we quantified the influence of B. truncatus population genetics, spatial distribution, environmental bacterial communities, and infection status on the snails microbiota structure. Our results show that the genetic structure of B. truncatus populations, and to a lower extent geographic distribution, are the main factors explaining the snails microbiota compositions. Neither the environmental bacterial communities nor trematode infection status significantly contributed to microbiota structure. A portion of the variance in microbiota composition remains unexplained, suggesting that additional ecological or intrinsic factors might be involved. These findings provide new insights into the drivers of microbiota structure in natural populations and highlight the complexity of host-microbiota-environment interactions. Key-words: Bulinus truncatus, Microbiota, Spatial structure, Population genetics, Trematodes, Multiple regressions on distance matrices

ecology↗

bioRxiv2024

Mechanistic origin and preimplantation development of uniparental and polyploid blastomeres

Whole-genome (WG) abnormalities, such as uniparental diploidy and triploidy, cause fetal death. Occasionally, they coexist with biparental diploid cells in live births. Understanding the origin and early development of WG abnormal blastomeres is crucial for explaining the formation of androgenotes, gynogenotes, triploidy, chimerism, and mixoploidy. By haplotyping 118 blastomeres from first cleavages, we identified various mechanisms of heterogoneic divisions that lead to WG abnormal blastomeres or their coexistence with normal blastomeres in both multipolar and bipolar cleaving zygotes. After culturing the totipotent blastomeres to three preimplantation stages and performing transcriptome profiling on over 600 cells, we discovered that stress responses contribute to developmental impairment in WG abnormal cells, resulting in either cell arrest or blastocyst formation. Some first-cleavage-derived WG abnormal blastomeres can survive early development and progress to blastocysts. Their potential dominance in preimplantation embryos represents an overlooked cause of abnormal development. Haplotype based screening could further increase pregnancy rates.

genetics↗

bioRxiv2023

Impact of blood meals taken on ivermectin-treated livestock on survival and fecundity of the malaria vector Anopheles coluzzii under laboratory conditions

Treatment of livestock with endectocides such as ivermectin is viewed as a complementary vector control approach to address residual transmission of malaria. However, efficacy of this treatment may vary between animal species. Hence, our purpose was to investigate the effects of ivermectin treatments of common livestock species on life history traits of the opportunistic malaria vector Anopheles coluzzii. Sheep, goats and pigs were treated using injectable veterinary ivermectin formulation at the species-specific doses (recommended dose for all species and high dose in pig). Mosquito batches were exposed to treated and control (not injected) animals at different days after treatment. Daily mosquito mortality was recorded and fecundity assessed through the count of gravid females and the number of eggs they developed. The recommended dose of ivermectin induced a significant decrease in mosquito survival for up to 7 days after injection (DAI), with a decrease of 89.7%, 66.7%, and 48.4% in treated pigs, goats and sheep, respectively, compared to control animals. In treated pigs, the triple therapeutic dose decreased mosquito survival of 68.97% relatively to controls up to 14 DAI. The average number in gravid females Anopheles that survived after feeding on treated animals were reduced when blood-meals were taken on sheep (2.57% and 42.03% at 2 and 7 DAI), or on goats (decrease of the 28.28% and 73.64% respectively at 2 and 7 DAI). This study shows that ivermectin treatments to animals negatively impacts An. coluzzii life history traits and could reduce vector densities in areas where livestock live near humans. However, due to short-term efficacy of single dose treatments, repeated treatments and potentially increased dosages would be required to span the transmission season. The use of long-acting ivermectin formulations is discussed as a mean for extending efficacy while remaining cost effective.

systems biology↗

bioRxiv2023

Mosquito aging modulates the development, virulence and transmission potential of pathogens

Host age variation is a striking source of heterogeneity that can shape the evolution and transmission dynamic of pathogens. Compared to vertebrate systems, our understanding of the impact of host age on invertebrate-pathogen interactions remains limited. We examined the influence of mosquito age on key life-history traits driving human malaria transmission. Females of Anopheles coluzzii, a major malaria vector, belonging to three age classes (4, 8, and 12 day-old), were experimentally infected with Plasmodium falciparum field isolates. Our findings revealed reduced competence in 12-day-old mosquitoes, characterized by lower oocyst/sporozoite rates and intensities compared to younger mosquitoes. Despite shorter median longevities in older age classes, infected 12-day-old mosquitoes exhibited improved survival, suggesting that the infection might act as a fountain of youth for older mosquitoes specifically. The timing of sporozoite appearance in the salivary glands remained consistent across mosquito age classes, with an extrinsic incubation period of approximately 13 days. Integrating these results into an epidemiological model revealed a lower vectorial capacity for older mosquitoes compared to younger ones, albeit still substantial due to extended longevity in the presence of infection. Considering age heterogeneity provides valuable insights for ecological and epidemiological studies, informing targeted control strategies to mitigate pathogen transmission.

ecology↗

bioRxiv2023

The paradox of plant preference: the malaria vectors Anopheles gambiae and Anopheles coluzzii select suboptimal food sources for their survival and reproduction

Anopheles gambiae s.l. mosquitoes, the primary malaria vectors in sub-Saharan Africa, exhibit selectivity among plant species as potential food sources. However, it remains unclear if their preference aligns with optimal nutrient intake and survival. Following an extensive screening of the effects of 31 plant species on An. coluzzii in Burkina Faso, we selected three species for their contrasting effects on mosquito survival, namely Ixora coccinea, Caesalpinia pulcherrima and Combretum indicum. We assessed the sugar content of these plants and their impact on mosquito fructose-positivity, survival, and insemination rate, using Anopheles coluzzii and Anopheles gambiae, and with glucose 5% and water as controls. Plants displayed varying sugar content and differentially affected the survival, sugar intake and insemination rate of mosquitoes. All three plants were more attractive to mosquitoes than controls, with An. gambiae being more responsive than An. coluzzii. Notably, C. indicum was the most attractive but had the lowest sugar content and offered the lowest survival, insemination rate, and fructose positivity. Our findings unveil a performance-preference mismatch in An. coluzzii and An. gambiae regarding plant food sources. Several possible reasons for this negative correlation between performance and preference are discussed.

ecology↗

bioRxiv2023

An Ionic Lock Mediates Interdomain Interactions in G protein αi subunits and Determines Gαi Subtype Signaling Specificity

Highly homologous members of the Gi family, Gi1-3, have distinct tissue distributions and physiological functions, yet the functional properties of these proteins with respect to GDP/GTP binding and regulation of adenylate cyclase are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gi1 effector, however, it is poorly activated by Gi2. Here, in a proteomic proximity labeling screen we observed a strong preference for Gi1 relative to Gi2 with respect to engagement of a broad range of potential targets. We investigated the mechanistic basis for this selectivity using PRG as a representative target. Substitution of either the helical domain (HD) from Gi1 into Gi2 or substitution of a single amino acid, A230 in Gi2 to the corresponding D in Gi1, largely rescues PRG activation and interactions with other Gi targets. Molecular dynamics simulations combined with Bayesian network models revealed that in the GTP bound state, dynamic separation at the HD-Ras-like domain (RLD) interface is prevalent in Gi2 relative to Gi1 and that mutation of A230s4h3.3 to D in Gi2 stabilizes HD-RLD interactions through formation of an ionic interaction with R145HD.11 in the HD. These interactions in turn modify the conformation of Switch III. These data support a model where D229s4h3.3 in Gi1 interacts with R144HD.11 stabilizes a network of interactions between HD and RLD to promote protein target recognition. The corresponding A230 in Gi2 is unable to form the "ionic lock" to stabilize this network leading to an overall lower efficacy with respect to target interactions. This study reveals distinct mechanistic properties that could underly differential biological and physiological consequences of activation of Gi1 or Gi2 by GPCRs.

pharmacology and toxicology↗

bioRxiv2023

Multiple hosts, multiple impacts: the role of vertebrate host diversity in shaping mosquito life history and pathogen transmission

The transmission of malaria parasites from mosquito to human is largely determined by the dietary specialization of Anopheles mosquitoes to feed on humans. Few studies have explored the impact of blood meal sources on the fitness of both the parasite and the mosquito. Our study investigated the effects of 3-4 consecutive blood meals from one of four vertebrate species (human, cattle, sheep, or chicken) on several fitness traits, including mosquito feeding rate, blood meal size, susceptibility to wild isolates of Plasmodium falciparum, survival, fecundity, F1 offspring development time, and size. Our findings revealed no significant effect on parasite development. Similarly, parasite exposure had no overall effects on mosquito fitness. However, blood meal type did have a strong impact on mosquito feeding rate, survival, lifetime fecundity, and offspring size. Specifically, mosquitoes that were fed successive chicken blood meals produced fewer eggs and fewer and smaller F1 adults compared to those fed human blood. Combining our results in a theoretical model, we show a decrease in the vectorial capacity of mosquitoes fed chicken or cow blood and an increase in the capacity of those fed sheep blood compared to those fed human blood. These findings emphasize the importance of considering the diversity of blood meal sources in understanding mosquito ecology and their role in the transmission intensity of malaria parasites.

evolutionary biology↗

bioRxiv2022

Intervention reducing malaria parasite load in vector mosquitoes: no impact on Plasmodium falciparum extrinsic incubation period and the survival of Anopheles gambiae

In the fight against malaria, transmission blocking interventions (TBIs) are promising approaches to complement conventional tools. They aim to prevent the infection of the vectors and thereby reduce the subsequent exposure of a human population to infectious mosquitoes. The effectiveness of these approaches has been shown to depend on the initial intensity of infection in mosquitoes, often measured as the mean number of oocysts resulting from an infectious blood meal prior to intervention. In mosquitoes exposed to a high infection load, current TBI candidates are expected to be ineffective at completely blocking infection but will decrease parasite load and therefore, potentially also affect key parameters of vector transmission. The present study aims to investigate the consequences of changes in oocyst intensity on downstream parasite development and mosquito survival. To address this, we experimentally produced different infection intensities in Anopheles gambiae females by diluting gametocytes from natural Plasmodium falciparum isolates and used a newly developed non-destructive method based on the exploitation of mosquito sugar feeding to track parasite and mosquito life history traits throughout sporogonic development. Our results indicate that P. falciparum extrinsic incubation period (EIP) and mosquito survival did not vary with parasite density but differed significantly between parasite isolates. Our results do not identify here unintended consequences of the decrease of parasite loads in mosquitoes on the parasite incubation period or on mosquito survival, two key parameters of vectorial capacity, and hence support the transmission blocking strategies to control malaria. Author summaryIn the fight against malaria, it is recognized that the use of several complementary strategies is necessary to significantly reduce transmission and improve human health. Among these, transmission blocking strategies aim at blocking the development of the parasites within the mosquito vectors. This approach should prevent infection in most of mosquitoes feeding on infectious hosts and thus block the transmission. However, in some cases it may only reduce parasite load without fully clearing the infection. Here we identified potential risks: if reducing parasite load would reduce the incubation period of the parasite in the mosquitoes or increase the longevity of the mosquitoes, undesirable consequences may occur with an increased efficiency of these mosquitoes to transmit parasites to human. We therefore tested these hypotheses and experimentally produced different infection loads in vector mosquitoes Anopheles gambiae by using dilutions of Plasmodium falciparum isolates from naturally infected human donors. We observed that the longevity of the mosquitoes and the incubation period of the parasites were not affected by the parasite load. This is not consistent with the unintended risks that we investigated and thus strengthens the potential of transmission blocking interventions in the toolbox to combat malaria.

evolutionary biology↗

bioRxiv2021

Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these issues an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions. Significance StatementEffective control of malaria is hampered by resistance to vector-targeted insecticides and parasite-targeted drugs. This situation is exacerbated by a critical lack of chemical diversity in both interventions and, as such, new interventions are badly needed. Recent laboratory studies have shown that an alternative approach based on treating Anopheles mosquitoes directly with antimalarial compounds can render the vector incapable of transmitting the Plasmodium parasites that cause malaria. While promising, showing that mosquito-targeted antimalarials remain effective against wild parasites and mosquitoes, including drug- and insecticide-resistant populations, respectively, is crucial to the future viability of this approach. In this study, carried out in the US and Burkina Faso, we show that antimalarial exposure is highly effective, even against extremely resistant mosquitoes, and can block transmission of drug-resistant parasites. By combining lab, and field-based studies in this way we have demonstrated that this novel approach can be effective in areas where conventional control measures are no longer as effective.

microbiology↗

bioRxiv2020

Using a non-destructive sugar-feeding assay for sporozoite detection and estimating the extrinsic incubation period of Plasmodium falciparum in mosquito vectors

Despite its epidemiological importance, the time Plasmodium parasites take to achieve development in the vector mosquito (the extrinsic incubation period, EIP) remains poorly characterized. A novel non-destructive assay designed to estimate EIP in single mosquitoes, and more broadly to study Plasmodium - Anopheles vectors interactions, is presented. The assay uses small pieces of cotton wool soaked in sugar solution to collect malaria sporozoites from individual mosquitoes during sugar feeding to monitor infection status over time. This technique has been tested across four natural malaria mosquito species of Africa and Asia, six parasite isolates of Plasmodium falciparum, and across a range of temperatures relevant to malaria transmission in field conditions. We find that monitoring individual infectious mosquitoes is feasible, although due to the frequency of mosquito sugar feeding and inter-individual variation in infection intensity, there is inherent risk that this technique will result in some false negatives. The sensitivity rate ranged from 0.27 to 0.81 depending on mosquito species and on infection intensity in mosquitoes used to collect saliva. Using this non-destructive technique, the estimated median extrinsic incubation period of P. falciparum at 27{degrees}C was 11 to 14 days depending on mosquito species and parasite isolate. Long-term individual tracking also revealed that sporozoite transfer onto cotton wool can occur at least until day 40 post-infection. In addition to contributing to a better understanding of EIP and mosquito to human transmission with implications for improving epidemiological models, this technique also allows to link different transmission traits at the mosquito individual level. As one example, we found a significant relationship between EIP and mosquito lifespan, with short individual EIP associated with short mosquito lifespan. Correlations between mosquito/parasite traits often reveal trade-offs and constraints and have important implications for understanding the evolution of parasite transmission strategies.

molecular biology↗

bioRxiv2020

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

Anopheles mosquitoes have transmitted Plasmodium parasites for millions of years, yet it remains unclear whether they suffer fitness costs to infection. Here we report that the fecundity of virgin and mated females of two important vectors--Anopheles gambiae and Anopheles stephensi--is not affected by infection with Plasmodium falciparum, demonstrating that these human malaria parasites do not inflict reproductive costs to their natural mosquito hosts. Additionally, parasite development is not impacted by mating status. However, in field studies using different P. falciparum isolates in Anopheles coluzzii, we find that Mating-Induced Stimulator of Oogenesis (MISO), a female reproductive gene strongly induced after mating by the sexual transfer of the steroid hormone 20-hydroxyecdysone (20E), protects females from incurring fecundity costs to infection. MISO-silenced females produce fewer eggs as they become increasingly infected with P. falciparum, while parasite development is not impacted by this gene silencing. Interestingly, previous work had shown that sexual transfer of 20E has specifically evolved in Cellia species of the Anopheles genus, driving the co-adaptation of MISO. Our data therefore suggest that evolution of male-female sexual interactions may have promoted Anopheles tolerance to P. falciparum infection in the Cellia subgenus, which comprises the most important malaria vectors. Author summaryPlasmodium falciparum, the deadliest form of human malaria, is transmitted when female Anopheles mosquitoes bite people and take a blood meal in order to develop eggs. To date, it is still poorly understood whether Anopheles mosquitoes that get infected with P. falciparum suffer fitness costs. Here, we find that the number of eggs produced by Anopheles gambiae and Anopheles stephensi females is not affected by P. falciparum infection, and that the mating status of the mosquitoes does not impact the parasite. However, in field experiments infecting a related species, Anopheles coluzzii, with P. falciparum using blood from donors in Burkina Faso, we find that interfering with the expression of a gene normally triggered by the sexual transfer of the steroid hormone 20-hydroxyecdysone induces increasing costs to egg development as females become more infected with P. falciparum, with no impacts on the parasite. The results of our study suggest that pathways triggered by mating may help Anopheles prevent reproductive costs associated with P. falciparum infection, providing new insights into evolutionary strategies adopted by anophelines in the face of a longstanding association with Plasmodium parasites.

microbiology↗

bioRxiv2019

Opening Pandora’s Box: Distribution of Plasmodium gametocytes in bloodstream

Malaria, a vector borne disease caused by Plasmodium spp., remains a major global cause of morbidity and mortality. Optimization of the disease control strategies requires a thorough understanding of the fundamental processes underlying parasite transmission. Although the number of transmissible stages of Plasmodium (gametocyte) in human blood is frequently used as an indicator of human-to-mosquito transmission potential, this relationship is not always clear. Important efforts have been made to develop molecular tools to fine-tune gametocyte densities estimation and therefore improve the prediction of mosquito infection rates, but a significant level of uncertainty around this estimate remains. Here we show with both human and avian malaria system that the within-vertebrate host distribution of gametocytes could explain much of this uncertainty. By comparing gametocyte densities in bloodstream between different body parts, we found a difference by nearly 50% in humans and by more than 15% in birds. An estimation of gametocyte density from only one blood sample, as is usually the case, could therefore drastically over- or underestimated the infectivity of gametocyte carriers. This might have important consequences on the epidemiology of the disease since we show, using the avian malaria system, that this variation influences the transmission of the parasite to the mosquito vector. In the light of our results, we argue that it is essential to consider the heterogeneous distribution of gametocyte to improve human diagnosis, identify infectious reservoirs and to test new malaria control strategies.

evolutionary biology↗

bioRxiv2019

High Plasmodium infection intensity in naturally infected malaria vectors in Africa

The population dynamics of human-to-mosquito malaria transmission in the field has important implications for the genetics, epidemiology and control of malaria. The number of oocysts in oocysts positive mosquitoes developing from a single, naturally acquired infectious blood meal (herein referred to as parasite exposure) greatly influence the effectiveness of transmission blocking interventions but still remains poorly documented. During a year-long analysis of malaria parasite transmission in Burkina Faso we caught and dissected wild malaria vectors to assess Plasmodium oocysts prevalence and load (the number of oocysts counted in mosquitoes with detectable oocysts) and the prevalence of salivary gland sporozoites. This was compared to malaria endemicity in the human population assessed in cross-sectional surveys. Data was analyzed using a novel transmission mathematical model to estimate the per-bite transmission probability and the average parasite exposure of mosquitoes for each location. Observed oocysts load and estimated parasite exposure in naturally infected mosquitoes is substantially higher than previous estimates (ranging from 3.2 to 24.5 according to seasons and locations) and indicates a strong positive association between parasite exposure of mosquitoes and parasite prevalence in human. This work suggests that highly infected mosquitoes may have a greater influence on the epidemiology and genetics of the parasite and that novel partially effective transmission blocking interventions may become more effective at halting transmission as parasite exposure is diminished.

ecology↗

bioRxiv2018

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↗

bioRxiv2017

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↗

bioRxiv2017

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↗