scholarly journals Assessment of Plasmodium falciparum Infection and Fitness of Genetically Modified Anopheles gambiae Aimed at Mosquito Population Replacement

2021 ◽  
Vol 2 ◽  
Author(s):  
Sofia Tapanelli ◽  
Maria Grazia Inghilterra ◽  
Julia Cai ◽  
James Philpott ◽  
Paolo Capriotti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life History ◽  
Anopheles Gambiae ◽  
Genetically Modified ◽  
Parasite Infection ◽  
Mosquito Population ◽  
Life History Trait ◽  
Gene Drive ◽  
Population Replacement ◽  
The Impact

Genetically modified (GM) mosquitoes expressing anti-plasmodial effectors propagating through wild mosquito populations by means of gene drive is a promising tool to support current malaria control strategies. The process of generating GM mosquitoes involves genetic transformation of mosquitoes from a laboratory colony and, often, interbreeding with other GM lines to cross in auxiliary traits. These mosquito colonies and GM lines thus often have different genetic backgrounds and GM lines are invariably highly inbred, which in conjunction with their independent rearing in the laboratory may translate to differences in their susceptibility to malaria parasite infection and life history traits. Here, we show that laboratory Anopheles gambiae colonies and GM lines expressing Cas9 and Cre recombinase vary greatly in their susceptibility to Plasmodium falciparum NF54 infection. Therefore, the choice of mosquitoes to be used as a reference when conducting infection or life history trait assays requires careful consideration. To address these issues, we established an experimental pipeline involving genetic crosses and genotyping of mosquitoes reared in shared containers throughout their lifecycle. We used this protocol to examine whether GM lines expressing the antimicrobial peptide (AMP) Scorpine in the mosquito midgut interfere with parasite infection and mosquito survival. We demonstrate that Scorpine expression in the Peritrophin 1 (Aper1) genomic locus reduces both P. falciparum sporozoite prevalence and mosquito lifespan; both these phenotypes are likely to be associated with the disturbance of the midgut microbiota homeostasis. These data lead us to conclude that the Aper1-Sco GM line could be used in proof-of-concept experiments aimed at mosquito population replacement, although the impact of its reduced fitness on the spread of the transgene through wild populations requires further investigation.

scholarly journals Assessment of Plasmodium falciparum infection and fitness of genetically modified Anopheles gambiae aimed at mosquito population replacement

2021 ◽  
Author(s):  
Sofia Tapanelli ◽  
Maria Grazia Inghilterra ◽  
Julia Cai ◽  
James Philpott ◽  
Paolo Capriotti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life History ◽  
Anopheles Gambiae ◽  
Genetically Modified ◽  
Parasite Infection ◽  
Mosquito Population ◽  
Life History Trait ◽  
Gene Drive ◽  
Population Replacement ◽  
The Impact

Genetically modified (GM) mosquitoes expressing anti-plasmodial effectors propagating through wild mosquito populations by means of gene drive is a promising tool to support current malaria control strategies. The process of generating GM mosquitoes involves genetic transformation of mosquitoes from a laboratory colony and, often, interbreeding with other GM lines to cross in auxiliary traits. These mosquito colonies and GM lines thus often have different genetic backgrounds and GM lines are invariably highly inbred, which in conjunction with their independent rearing in the laboratory may translate to differences in their susceptibility to malaria parasite infection and life history traits. Here, we show that laboratory Anopheles gambiae colonies and GM lines expressing Cas9 and Cre recombinase vary greatly in their susceptibility to Plasmodium falciparum NF54 infection. Therefore, the choice of mosquitoes to be used as a reference when conducting infection or life history trait assays requires careful consideration. To address these issues, we established an experimental pipeline involving genetic crosses and genotyping of mosquitoes reared in shared containers throughout their lifecycle. We used this protocol to examine whether GM lines expressing the antimicrobial peptide (AMP) Scorpine in the mosquito midgut interfere with parasite infection and mosquito survival. We demonstrate that Scorpine expression in the Peritrophin 1 (Aper1) genomic locus reduces both P. falciparum sporozoite prevalence and mosquito lifespan; both these phenotypes are likely to be associated with the disturbance of the midgut microbiota homeostasis. These data lead us to conclude that the Aper1-Sco GM line could be used in proof-of-concept experiments aimed at mosquito population replacement, although the impact of its reduced fitness on the spread of the transgene through wild populations requires further investigation.

scholarly journals Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Matthew P. Su ◽  
Marcos Georgiades ◽  
Judit Bagi ◽  
Kyros Kyrou ◽  
Andrea Crisanti ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Population Control ◽  
Beat Frequency ◽  
Phenotypic Traits ◽  
Gene Drive ◽  
Anopheles Gambiae S.L ◽  
Female Genotype ◽  
Female Specific ◽  
The Impact ◽  
Dose Dependent

Abstract Background Release of gene-drive mutants to suppress Anopheles mosquito reproduction is a promising method of malaria control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. At a behavioural level, gene-drive carrying mutants should be at least as sexually attractive as the wildtype populations they compete against, with a key element of Anopheles copulation being acoustic courtship. We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages. Methods Anopheles rely on flight tones produced by the beating of their wings for acoustic mating communication. We assessed the impact of disrupting a female-specific isoform of the doublesex gene (dsxF) on the wing beat frequency (WBF; measured as flight tone) of males (XY) and females (XX) in homozygous dsxF− mutants (dsxF−/−), heterozygous dsxF− carriers (dsxF+/−) and G3 dsxF+ controls (dsxF+/+). To exclude non-genetic influences, we controlled for temperature and wing length. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes. Results A previous study showed an altered phenotype only for dsxF−/− females, who appear intersex, suggesting that the female-specific dsxF allele is haplosufficient. We identified significant, dose-dependent increases in the WBF of both dsxF−/− and dsxF+/− females compared to dsxF+/+ females. All female WBFs remained significantly lower than male equivalents, though. Males showed stronger phonotactic responses to the WBFs of control dsxF+/+ females than to those of dsxF+/− and dsxF−/− females. We found no evidence of phonotaxis in any female genotype. No male genotypes displayed any deviations from controls. Conclusions A prerequisite for anopheline copulation is the phonotactic attraction of males towards female flight tones within mating swarms. Reductions in mutant acoustic attractiveness diminish their mating efficiency and thus the efficacy of population control efforts. Caged population assessments may not successfully reproduce natural mating scenarios. We propose to amend existing testing protocols to better reflect competition between mutants and target populations. Our findings confirm that dsxF disruption has no effect on males; for some phenotypic traits, such as female WBFs, the effects of dsxF appear dose-dependent rather than haplosufficient.

scholarly journals Contrasting effects of the alkaloid ricinine on the capacity of Anopheles gambiae s.l. to transmit Plasmodium falciparum

2021 ◽  
Author(s):  
Domonbabele François de Sales Hien ◽  
Prisca S. L. Paré ◽  
Amanda Cooper ◽  
Benjamin K. Koama ◽  
Edwige Guissou ◽  
...  
Keyword(s):  
Growth Rate ◽  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Ricinus Communis ◽  
Control Agent ◽  
Phenotypic Traits ◽  
Anopheles Coluzzii ◽  
Vector Borne Diseases ◽  
Anopheles Gambiae S.L ◽  
The Impact

Abstract Background: Besides feeding on blood, females of the malaria vector Anopheles gambiae s.l. readily feed on natural sources of plant sugars. The impact of toxic secondary phytochemicals contained in plant-derived sugars on mosquito physiology and on the development of Plasmodium parasites remains elusive. The focus of this study was to explore the influence of the alkaloid ricinine, found in the nectar of the castorbean Ricinus communis, on the mosquito ability to transmit Plasmodium falciparum. Methods: Females of Anopheles gambiae and its sibling species Anopheles coluzzii were exposed to ricinine through sugar feeding assays to assess the effect of this phytochemical on mosquito survival, the level of P. falciparum infection, and the growth rate of the parasite. Results: Ricinine induced a significant reduction in the longevity of both Anopheles species. Ricinine caused acceleration in the parasite growth rate with an earlier invasion of the salivary glands in both species. At a concentration of 0.04 g l-1 in An. coluzzii, ricinine had no effect on mosquito infection, while 0.08 g l-1 ricinine-5% glucose solution induced a 14% increase in An. gambiae infection rate. Conclusions: Overall, our findings reveal that consumption of certain nectar phytochemicals can have unsuspected and contrasting effects on key phenotypic traits that govern the intensity of malaria transmission. Further studies will be required before concluding on the putative role of ricinine as a novel control agent, including the development of ricinine-based toxic and transmission-blocking sugar baits. Testing other secondary phytochemicals in plant nectar will provide a broader understanding of the impact, which plants can have on the transmission of vector-borne diseases.

scholarly journals Contrasting effects of the alkaloid ricinine on the capacity of Anopheles gambiae and Anopheles coluzzii to transmit Plasmodium falciparum

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Domonbabele F. D. S. Hien ◽  
Prisca S. L. Paré ◽  
Amanda Cooper ◽  
Benjamin K. Koama ◽  
Edwige Guissou ◽  
...  
Keyword(s):  
Growth Rate ◽  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Ricinus Communis ◽  
Control Agent ◽  
Phenotypic Traits ◽  
Anopheles Coluzzii ◽  
Vector Borne Diseases ◽  
Vector Borne ◽  
The Impact

Abstract Background Besides feeding on blood, females of the malaria vector Anopheles gambiae sensu lato readily feed on natural sources of plant sugars. The impact of toxic secondary phytochemicals contained in plant-derived sugars on mosquito physiology and the development of Plasmodium parasites remains elusive. The focus of this study was to explore the influence of the alkaloid ricinine, found in the nectar of the castor bean Ricinus communis, on the ability of mosquitoes to transmit Plasmodium falciparum. Methods Females of Anopheles gambiae and its sibling species Anopheles coluzzii were exposed to ricinine through sugar feeding assays to assess the effect of this phytochemical on mosquito survival, level of P. falciparum infection and growth rate of the parasite. Results Ricinine induced a significant reduction in the longevity of both Anopheles species. Ricinine caused acceleration in the parasite growth rate with an earlier invasion of the salivary glands in both species. At a concentration of 0.04 g l−1 in An. coluzzii, ricinine had no effect on mosquito infection, while 0.08 g l−1 ricinine-5% glucose solution induced a 14% increase in An. gambiae infection rate. Conclusions Overall, our findings reveal that consumption of certain nectar phytochemicals can have unexpected and contrasting effects on key phenotypic traits that govern the intensity of malaria transmission. Further studies will be required before concluding on the putative role of ricinine as a novel control agent, including the development of ricinine-based toxic and transmission-blocking sugar baits. Testing other secondary phytochemicals in plant nectar will provide a broader understanding of the impact which plants can have on the transmission of vector-borne diseases. Graphical abstract

scholarly journals Infection Intensity-Dependent Responses of Anopheles gambiae to the African Malaria Parasite Plasmodium falciparum

2011 ◽  
Vol 79 (11) ◽  
pp. 4708-4715 ◽  
Author(s):  
Antonio M. Mendes ◽  
Parfait H. Awono-Ambene ◽  
Sandrine E. Nsango ◽  
Anna Cohuet ◽  
Didier Fontenille ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Transcriptional Response ◽  
Infection Intensity ◽  
Mosquito Vector ◽  
Content Type ◽  
Parasite Plasmodium Falciparum ◽  
Control And Prevention ◽  
Functional Classes ◽  
The Impact

ABSTRACTMalaria remains a devastating disease despite efforts at control and prevention. Extensive studies using mostly rodent infection models reveal that successfulPlasmodiumparasite transmission by the African mosquito vectorAnopheles gambiaedepends on finely tuned vector-parasite interactions. Here we investigate the transcriptional response ofA. gambiaeto geographically relatedPlasmodium falciparumpopulations at various infection intensities and different infection stages. These responses are compared with those of mosquitoes infected with the rodent parasitePlasmodium berghei. We demonstrate that mosquito responses are largely dependent on the intensity of infection. A major transcriptional suppression of genes involved in the regulation of midgut homeostasis is detected in low-intensityP. falciparuminfections, the most common type of infection in Africa. Importantly, genes transcriptionally induced during these infections tend to be phylogenetically unique toA. gambiae. These data suggest that coadaptation between vectors and parasites may act to minimize the impact of infection on mosquito fitness by selectively suppressing specific functional classes of genes. RNA interference (RNAi)-mediated gene silencing provides initial evidence for important roles of the mosquito G protein-coupled receptors (GPCRs) in controlling infection intensity-dependent antiparasitic responses.

scholarly journals Mapping the adaptive landscape of a major agricultural pathogen reveals evolutionary constraints across heterogeneous environments

2021 ◽  
Author(s):  
Anik Dutta ◽  
Fanny E. Hartmann ◽  
Carolina Sardinha Francisco ◽  
Bruce A. McDonald ◽  
Daniel Croll
Keyword(s):  
Life History ◽  
Large Scale ◽  
Life History Traits ◽  
Genetic Correlations ◽  
Stress Factors ◽  
Life History Trait ◽  
Adaptive Landscape ◽  
Heterogeneous Environments ◽  
Growth Responses ◽  
Trade Offs

AbstractThe adaptive potential of pathogens in novel or heterogeneous environments underpins the risk of disease epidemics. Antagonistic pleiotropy or differential resource allocation among life-history traits can constrain pathogen adaptation. However, we lack understanding of how the genetic architecture of individual traits can generate trade-offs. Here, we report a large-scale study based on 145 global strains of the fungal wheat pathogen Zymoseptoria tritici from four continents. We measured 50 life-history traits, including virulence and reproduction on 12 different wheat hosts and growth responses to several abiotic stressors. To elucidate the genetic basis of adaptation, we used genome-wide association mapping coupled with genetic correlation analyses. We show that most traits are governed by polygenic architectures and are highly heritable suggesting that adaptation proceeds mainly through allele frequency shifts at many loci. We identified negative genetic correlations among traits related to host colonization and survival in stressful environments. Such genetic constraints indicate that pleiotropic effects could limit the pathogen’s ability to cause host damage. In contrast, adaptation to abiotic stress factors was likely facilitated by synergistic pleiotropy. Our study illustrates how comprehensive mapping of life-history trait architectures across diverse environments allows to predict evolutionary trajectories of pathogens confronted with environmental perturbations.

scholarly journals The malaria burden of Amerindian groups of three Venezuelan states: a descriptive study based on programmatic data

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Juan C. Gabaldón-Figueira ◽  
Carlos Chaccour ◽  
Jorge Moreno ◽  
Maria Villegas ◽  
Leopoldo Villegas
Keyword(s):  
Risk Factors ◽  
Plasmodium Falciparum ◽  
Malaria Incidence ◽  
Hot Spot ◽  
Public Health Problem ◽  
Epidemiological Data ◽  
Descriptive Study ◽  
Malaria Burden ◽  
Indigenous Groups ◽  
The Impact

Abstract Background Fifty-three percent of all cases of malaria in the Americas in 2019 came from Venezuela, where the epidemic is heavily focused south of the Orinoco river, and where most of the country’s Amerindian groups live. Although the disease is known to represent a significant public health problem among these populations, little epidemiological data exists on the subject. This study aims to provide information on malaria incidence, geospatial clustering, and risk factors associated to Plasmodium falciparum infection among these groups. Methods This is a descriptive study based on the analysis of published and unpublished programmatic data collected by Venezuelan health authorities and non-government organizations between 2014 and 2018. The Annual Parasite Index among indigenous groups (API-i) in municipalities of three states (Amazonas, Bolivar, and Sucre) were calculated and compared using the Kruskal Wallis test, risk factors for Plasmodium falciparum infection were identified via binomial logistic regression and maps were constructed to identify clusters of malaria cases among indigenous patients via Moran’s I and Getis-Ord’s hot spot analysis. Results 116,097 cases of malaria in Amerindian groups were registered during the study period. An increasing trend was observed between 2014 and 2016 but reverted in 2018. Malaria incidence remains higher than in 2014 and hot spots were identified in the three states, although more importantly in the south of Bolivar. Most cases (73.3%) were caused by Plasmodium vivax, but the Hoti, Yanomami, and Eñepa indigenous groups presented higher odds for infection with Plasmodium falciparum. Conclusion Malaria cases among Amerindian populations increased between 2014 and 2018 and seem to have a different geographic distribution than those among the general population. These findings suggest that tailored interventions will be necessary to curb the impact of malaria transmission in these groups.

scholarly journals Anopheles gambiae Genome Conservation as a Resource for Rational Gene Drive Target Site Selection

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 97
Author(s):  
Nace Kranjc ◽  
Andrea Crisanti ◽  
Tony Nolan ◽  
Federica Bernardini
Keyword(s):  
Anopheles Gambiae ◽  
Data Storage ◽  
Genomic Variation ◽  
Malaria Vectors ◽  
Anopheles Coluzzii ◽  
Structural Constraints ◽  
Gene Drive ◽  
Genetic Traits ◽  
A Genome ◽  
Insight Into

The increase in molecular tools for the genetic engineering of insect pests and disease vectors, such as Anopheles mosquitoes that transmit malaria, has led to an unprecedented investigation of the genomic landscape of these organisms. The understanding of genome variability in wild mosquito populations is of primary importance for vector control strategies. This is particularly the case for gene drive systems, which look to introduce genetic traits into a population by targeting specific genomic regions. Gene drive targets with functional or structural constraints are highly desirable as they are less likely to tolerate mutations that prevent targeting by the gene drive and consequent failure of the technology. In this study we describe a bioinformatic pipeline that allows the analysis of whole genome data for the identification of highly conserved regions that can point at potential functional or structural constraints. The analysis was conducted across the genomes of 22 insect species separated by more than hundred million years of evolution and includes the observed genomic variation within field caught samples of Anopheles gambiae and Anopheles coluzzii, the two most dominant malaria vectors. This study offers insight into the level of conservation at a genome-wide scale as well as at per base-pair resolution. The results of this analysis are gathered in a data storage system that allows for flexible extraction and bioinformatic manipulation. Furthermore, it represents a valuable resource that could provide insight into population structure and dynamics of the species in the complex and benefit the development and implementation of genetic strategies to tackle malaria.

scholarly journals The early sporogonic cycle of Plasmodium falciparum in laboratory‐infected Anopheles gambiae : an estimation of parasite efficacy

1998 ◽  
Vol 3 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Louis Clément Gouagna ◽  
Louis Clément Gouagna ◽  
Bert Mulder ◽  
Bert Mulder ◽  
Elisabeth Noubissi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae
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