Catteruccia, Flaminia

Person:
Catteruccia, Flaminia

Last Name

Catteruccia

First Name

Flaminia

Name

Catteruccia, Flaminia

Full item page

Search Results

Now showing 1 - 10 of 13

Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission
(Springer Nature, 2019-02-27) Paton, Douglas; Itoe, Maurice; Holmdahl, Inga; Buckee, Caroline; Catteruccia, Flaminia
Every year the bites of Anopheles mosquitoes kill hundreds of thousands of people, mostly young African children, by transmitting deadly Plasmodium falciparum malaria parasites. Since the turn of the century, efforts to prevent transmission of these parasites via the mass distribution of insecticide-treated bed nets have been extremely successful, causing an unprecedented reduction in malaria deaths1. However, resistance to insecticides has become widespread in Anopheles populations2-4, threatening a global resurgence of the disease and making the generation of effective new malaria control tools an urgent public health priority. Here, we show that development of P. falciparum can be rapidly and completely blocked when Anopheles gambiae females uptake low concentrations of specific antimalarials from treated surfaces, simulating contact with a bed net. Mosquito exposure to atovaquone prior to or shortly after P. falciparum infection causes full parasite arrest in the female midgut, preventing transmission of infection. Similar transmission-blocking effects are achieved with other cytochrome B inhibitors, demonstrating that parasite mitochondrial function is a good target for parasite killing. Incorporating these effects into a model of malaria transmission dynamics predicts that the inclusion of Plasmodium inhibitors on mosquito nets would significantly mitigate the global health impact of insecticide resistance. This study identifies a powerful new strategy for blocking Plasmodium transmission by Anopheles females, with promising implications for malaria eradication efforts.
Evidence of natural Wolbachia infections in field populations of Anopheles gambiae
(Nature Pub. Group, 2014) Baldini, Francesco; Segata, Nicola; Pompon, Julien; Marcenac, Perrine; Robert Shaw, W.; Dabiré, Roch K.; Diabaté, Abdoulaye; Levashina, Elena A.; Catteruccia, Flaminia
Wolbachia are maternally transmitted intracellular bacteria that invade insect populations by manipulating their reproduction and immunity and thus limiting the spread of numerous human pathogens. Experimental Wolbachia infections can reduce Plasmodium numbers in Anopheles mosquitoes in the laboratory, however, natural Wolbachia infections in field anophelines have never been reported. Here we show evidence of Wolbachia infections in Anopheles gambiae in Burkina Faso, West Africa. Sequencing of the 16S rRNA gene identified Wolbachia sequences in both female and male germlines across two seasons, and determined that these sequences are vertically transmitted from mother to offspring. Whole-genome sequencing of positive samples suggests that the genetic material identified in An. gambiae belongs to a novel Wolbachia strain, related to but distinct from strains infecting other arthropods. The evidence of Wolbachia infections in natural Anopheles populations promotes further investigations on the possible use of natural Wolbachia–Anopheles associations to limit malaria transmission.
The Interaction between a Sexually Transferred Steroid Hormone and a Female Protein Regulates Oogenesis in the Malaria Mosquito Anopheles gambiae
(Public Library of Science, 2013) Baldini, Francesco; Gabrieli, Paolo; South, Adam; Valim, Clarissa; Mancini, Francesca; Catteruccia, Flaminia
Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that the mating-dependent pathway of egg development in these mosquitoes is regulated by the interaction between the steroid hormone 20-hydroxy-ecdysone (20E) transferred by males during copulation and a female Mating-Induced Stimulator of Oogenesis (MISO) protein. RNAi silencing of MISO abolishes the increase in oogenesis caused by mating in blood-fed females, causes a delay in oocyte development, and impairs the function of male-transferred 20E. Co-immunoprecipitation experiments show that MISO and 20E interact in the female reproductive tract. Moreover MISO expression after mating is induced by 20E via the Ecdysone Receptor, demonstrating a close cooperation between the two factors. Male-transferred 20E therefore acts as a mating signal that females translate into an increased investment in egg development via a MISO-dependent pathway. The identification of this male–female reproductive interaction offers novel opportunities for the control of mosquito populations that transmit malaria.
Engineering the control of mosquito-borne infectious diseases
(BioMed Central, 2014) Gabrieli, Paolo; Smidler, Andie; Catteruccia, Flaminia
Recent advances in genetic engineering are bringing new promise for controlling mosquito populations that transmit deadly pathogens. Here we discuss past and current efforts to engineer mosquito strains that are refractory to disease transmission or are suitable for suppressing wild disease-transmitting populations.
Dihydroisoxazole inhibitors of Anopheles gambiae seminal transglutaminase AgTG3
(BioMed Central, 2014) Le, Binh V; Klöck, Cornelius; Schatz, Alexandra; Nguyen, Jennifer B; Kakani, Evdoxia; Catteruccia, Flaminia; Khosla, Chaitan; Baxter, Richard HG
Background: Current vector-based malaria control strategies are threatened by the rise of biochemical and behavioural resistance in mosquitoes. Researching mosquito traits of immunity and fertility is required to find potential targets for new vector control strategies. The seminal transglutaminase AgTG3 coagulates male Anopheles gambiae seminal fluids, forming a ‘mating plug’ that is required for male reproductive success. Inhibitors of AgTG3 can be useful both as chemical probes of A. gambiae reproductive biology and may further the development of new chemosterilants for mosquito population control. Methods: A targeted library of 3-bromo-4,5-dihydroxoisoxazole inhibitors were synthesized and screened for inhibition of AgTG3 in a fluorescent, plate-based assay. Positive hits were tested for in vitro activity using cross-linking and mass spectrometry, and in vivo efficacy in laboratory mating assays. Results: A targeted chemical library was screened for inhibition of AgTG3 in a fluorescent plate-based assay using its native substrate, plugin. Several inhibitors were identified with IC50 < 10 μM. Preliminary structure-activity relationships within the library support the stereo-specificity and preference for aromatic substituents in the chemical scaffold. Both inhibition of plugin cross-linking and covalent modification of the active site cysteine of AgTG3 were verified. Administration of an AgTG3 inhibitor to A. gambiae males by intrathoracic injection led to a 15% reduction in mating plug transfer in laboratory mating assays. Conclusions: A targeted screen has identified chemical inhibitors of A. gambiae transglutaminase 3 (AgTG3). The most potent inhibitors are known inhibitors of human transglutaminase 2, suggesting a common binding pose may exist within the active site of both enzymes. Future efforts to develop additional inhibitors will provide chemical tools to address important biological questions regarding the role of the A. gambiae mating plug. A second use for transglutaminase inhibitors exists for the study of haemolymph coagulation and immune responses to wound healing in insects.
Concerning RNA-guided gene drives for the alteration of wild populations
(eLife Sciences Publications, Ltd, 2014) Esvelt, Kevin Michael; Smidler, Andie; Catteruccia, Flaminia; Church, George
Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology. DOI: http://dx.doi.org/10.7554/eLife.03401.001
Disrupting Mosquito Reproduction and Parasite Development for Malaria Control
(Public Library of Science, 2016) Childs, Lauren M.; Cai, Francisco Y.; Kakani, Evdoxia; Mitchell, Sara N.; Paton, Doug; Gabrieli, Paolo; Buckee, Caroline O.; Catteruccia, Flaminia
The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E) is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance.
Wolbachia infections in natural Anopheles populations affect egg laying and negatively correlate with Plasmodium development
(Nature Publishing Group, 2016) Shaw, W. Robert; Marcenac, Perrine; Childs, Lauren; Buckee, Caroline O.; Baldini, Francesco; Sawadogo, Simon P.; Dabiré, Roch K.; Diabaté, Abdoulaye; Catteruccia, Flaminia
The maternally inherited alpha-proteobacterium Wolbachia has been proposed as a tool to block transmission of devastating mosquito-borne infectious diseases like dengue and malaria. Here we study the reproductive manipulations induced by a recently identified Wolbachia strain that stably infects natural mosquito populations of a major malaria vector, Anopheles coluzzii, in Burkina Faso. We determine that these infections significantly accelerate egg laying but do not induce cytoplasmic incompatibility or sex-ratio distortion, two parasitic reproductive phenotypes that facilitate the spread of other Wolbachia strains within insect hosts. Analysis of 221 blood-fed A. coluzzii females collected from houses shows a negative correlation between the presence of Plasmodium parasites and Wolbachia infection. A mathematical model incorporating these results predicts that infection with these endosymbionts may reduce malaria prevalence in human populations. These data suggest that Wolbachia may be an important player in malaria transmission dynamics in Sub-Saharan Africa.
The reproductive tracts of two malaria vectors are populated by a core microbiome and by gender- and swarm-enriched microbial biomarkers
(Nature Publishing Group, 2016) Segata, Nicola; Baldini, Francesco; Pompon, Julien; Garrett, Wendy; Truong, Duy Tin; Dabiré, Roch K.; Diabaté, Abdoulaye; Levashina, Elena A.; Catteruccia, Flaminia
Microbes play key roles in shaping the physiology of insects and can influence behavior, reproduction and susceptibility to pathogens. In Sub-Saharan Africa, two major malaria vectors, Anopheles gambiae and An. coluzzii, breed in distinct larval habitats characterized by different microorganisms that might affect their adult physiology and possibly Plasmodium transmission. We analyzed the reproductive microbiomes of male and female An. gambiae and An. coluzzii couples collected from natural mating swarms in Burkina Faso. 16S rRNA sequencing on dissected tissues revealed that the reproductive tracts harbor a complex microbiome characterized by a large core group of bacteria shared by both species and all reproductive tissues. Interestingly, we detected a significant enrichment of several gender-associated microbial biomarkers in specific tissues, and surprisingly, similar classes of bacteria in males captured from one mating swarm, suggesting that these males originated from the same larval breeding site. Finally, we identified several endosymbiotic bacteria, including Spiroplasma, which have the ability to manipulate insect reproductive success. Our study provides a comprehensive analysis of the reproductive microbiome of important human disease vectors, and identifies a panel of core and endosymbiotic bacteria that can be potentially exploited to interfere with the transmission of malaria parasites by the Anopheles mosquito.
High-throughput Sorting of Mosquito Larvae for Laboratory Studies and for Future Vector Control Interventions
(BioMed Central, 2012) Marois, Eric; Scali, Christina; Soichot, Julien; Kappler, Christine; Levashina, Elena A; Catteruccia, Flaminia
Background: Mosquito transgenesis offers new promises for the genetic control of vector-borne infectious diseases such as malaria and dengue fever. Genetic control strategies require the release of large number of male mosquitoes into field populations, whether they are based on the use of sterile males (sterile insect technique, SIT) or on introducing genetic traits conferring refractoriness to disease transmission (population replacement). However, the current absence of high-throughput techniques for sorting different mosquito populations impairs the application of these control measures. Methods: A method was developed to generate large mosquito populations of the desired sex and genotype. This method combines flow cytometry and the use of Anopheles gambiae transgenic lines that differentially express fluorescent markers in males and females. Results: Fluorescence-assisted sorting allowed single-step isolation of homozygous transgenic mosquitoes from a mixed population. This method was also used to select wild-type males only with high efficiency and accuracy, a highly desirable tool for genetic control strategies where the release of transgenic individuals may be problematic. Importantly, sorted males showed normal mating ability compared to their unsorted brothers. Conclusions: The developed method will greatly facilitate both laboratory studies of mosquito vectorial capacity requiring high-throughput approaches and future field interventions in the fight against infectious disease vectors.