Biology subjects

Genta, F. A.

Publications and source records attributed to Genta, F. A..

3 recordsLinked to original sources

bioRxiv2026

Antiviral sugar baits to reduce arbovirus transmission: a proof-of-concept study

Dengue virus (DENV) and chikungunya virus (CHIKV) remain major global health threats, yet approved antiviral therapies are lacking. Antiviral sugar baits (AVSBs) represent a novel transmission-blocking strategy that exploits the natural sugar-feeding behaviour of mosquitoes to deliver antiviral compounds directly to the mosquito vector. In this study, we evaluated the antiviral efficacy of AVSBs containing JNJ-A07, {beta}-D-N4-hydroxycytidine (NHC), molnupiravir (MPV), and 4'-fluorouridine (4'FlU) in Aedes aegypti mosquitoes. An ex vivo mosquito gut model was used to select antiviral concentrations and to assess the ability of 4'FlU to reach the mosquito midgut following sugar feeding. AVSBs were subsequently evaluated for their effects on mosquito attractiveness, longevity, fecundity, and fertility, as well as their ability to suppress DENV and CHIKV infection in vivo. 4'FlU potently inhibited CHIKV replication in ex vivo mosquito guts and retained antiviral activity following sugar-bait administration. None of the antiviral compounds affected mosquito attraction to the bait, while only modest and compound-specific effects on mosquito fitness were observed. AVSBs containing JNJ-A07 significantly reduced DENV infection and dissemination, whereas 4'FlU-containing AVSBs significantly reduced CHIKV infection and viral loads. In contrast, NHC- and MPV-containing AVSBs did not exhibit antiviral activity in vivo. Collectively, these findings provide proof-of-concept for AVSBs as a novel strategy to reduce arbovirus transmission by targeting viral replication within the mosquito vector, suggesting that AVSBs could complement existing arbovirus control measures.

microbiology↗

bioRxiv2025

Exploiting nectar and blood feeding cues and phagostimulants to optimise Attractive Targeted Sugar Baits against a sand fly vector of leishmaniasis.

BackgroundLeishmaniasis presents a major public health problem for a large number of countries requiring effective integrated management of the vector, sand flies, for sustained control. Such strategies need to be economically and environmentally sustainable and adaptable to the behaviour of local vectors. One such tool is Attractive Targeted Sugar Baits (ATSB) that exploit the necessity of sand flies to acquire sugars between bloodmeals. Here we explored the kinetics and cues for sugar and blood feeding to improve the efficacy of ATSBs against sand flies. MethodsA fluorescent assay was developed to quantify sugarmeals to assess the feeding efficiency of colony-reared female Lutzomyia longipalpis sand flies. ResultsSand flies showed a range of preferences for different sugars presented on cotton wool and could be manipulated to deposit them into the crop and/or midgut. We found that the combination of 10% sucrose and 10% fructose allowed flies to obtain the largest sugarmeals taken to the crop. Sugarmeals were taken to both the crop and midgut when it contained 200 mM bovine serum albumin (BSA) as a source of protein and 1 mM adenosine triphosphate (ATP) as a phagostimulant. Using this combination, the efficacy of the ingested insecticide fipronil was significantly increased; reducing the 50% lethal concentration from 584 {micro}M to 1.65 {micro}M in a sugarmeal that promoted the simultaneous uptake of the insecticide into the midgut as well as the crop. ConclusionsIn this study we highlight the potential of understanding the cues used by vectors to sugar feed and blood feed. By incorporating blood feeding phagostimulants, such as BSA and ATP, in ATSB we vastly improve their killing efficiency against sand flies. This demonstrates a new approach to target these disease vectors. Author SummaryMany insect vectors of disease use sugars, such as nectar, as fuel to enable them to obtain blood, that in turn sustains parasite transmission. In most blood feeding Diptera sugars are diverted to the crop where it is stored and released into the midgut for energy whereas blood is taken directly to the midgut where it is digested to provide nutrients for egg development. For sand flies the cues required to switch between sugar and blood feeding programmes are unknown but if they were they could be exploited to improve Attractive Targeted Sugar Baits (ATSB) as a means of poisoning sand flies when they sugar feed. In this study we find that the sand fly, Lutzomyia longipalpis, uses a combination of physical cues (biting/piercing vs sucking) and meal composition to allow them to efficiently feed on nectar and blood. We show that they sense protein and adenosine triphosphate (ATP) to direct blood to the midgut and we demonstrate that this can be turned to our advantage to improve the lethality of ATSB. We show that inclusion of bovine serum albumin as a source of protein and the phagostimulant ATP can trick sand flies to blood feed on sugar and direct the insecticide fipronil to the midgut where it was 355-fold more potent than in sugar alone. These results show the potential of phagostimulants to improve the efficacy and selectivity of ATSB towards blood feeding arthropods, including sand flies, and highlights the value of understanding the feeding programmes of disease vectors in general.

zoology↗

bioRxiv2022

Genomic Analysis of Two Phlebotomine Sand Fly Vectors of Leishmania from the New and Old World

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the devastating kinetoplastid parasites of the genus Leishmania, the causative agents of diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. As no approved efficacious vaccine exists, available drugs are expensive and/or toxic, and resistance is emerging, management of sand fly populations to break transmission is currently the most effective disease control strategy. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two of the most important sand fly species: Phlebotomus papatasi, a cutaneous leishmaniasis vector, (distributed in the Middle East and North Africa) and Lutzomyia longipalpis, a visceral leishmaniasis vector (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites. Author SummaryThe leishmaniases are a group of neglected tropical diseases caused by protist parasites from the Genus Leishmania. Different Leishmania species present a wide clinical profile, ranging from mild, often self-resolving cutaneous lesions that can lead to protective immunity, to severe metastatic mucosal disease, to visceral disease that is ultimately fatal. Leishmania parasites are transmitted by the bites of sand flies, and as no approved vaccine exists, available drugs are toxic and/or expensive and resistance is emerging, new dual control strategies to combat these diseases must be developed, combining interventions on human infections and integrated sand fly population management. Effective vector control requires a good understanding of the biology of sand flies. To this end, we sequenced and annotated the genomes of two sand fly species that are important leishmaniasis vectors from the Old and New Worlds. These genomes allow us to better understand, at the genetic level, processes important in the vector biology of these species, such as finding hosts, blood-feeding, immunity, and detoxification. These genomic resources highlight the driving forces of evolution of two major Leishmania vectors and provide foundations for future research on how to better prevent leishmaniasis by control of the sand fly vectors.

genomics↗