VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center in 2023.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) is a Bioinformatics Resource Center funded by the National Institutes of Health with additional funding from the Wellcome Trust. VEuPathDB supports >600 organisms that comprise invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Since 2004, VEuPathDB has analyzed omics data from the public domain using contemporary bioinformatic workflows, including orthology predictions via OrthoMCL, and integrated the analysis results with analysis tools, visualizations, and advanced search capabilities. The unique data mining platform coupled with >3000 pre-analyzed data sets facilitates the exploration of pertinent omics data in support of hypothesis driven research. Comparisons are easily made across data sets, data types and organisms. A Galaxy workspace offers the opportunity for the analysis of private large-scale datasets and for porting to VEuPathDB for comparisons with integrated data. The MapVEu tool provides a platform for exploration of spatially resolved data such as vector surveillance and insecticide resistance monitoring. To address the growing body of omics data and advances in laboratory techniques, VEuPathDB has added several new data types, searches and features, improved the Galaxy workspace environment, redesigned the MapVEu interface and updated the infrastructure to accommodate these changes

Malaria vector species in Colombia: a review

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species' geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species

VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases

VectorBase is a National Institute of Allergy and Infectious Diseases supported Bioinformatics Resource Center (BRC) for invertebrate vectors of human pathogens. Now in its 11th year, VectorBase currently hosts the genomes of 35 organisms including a number of non-vectors for comparative analysis. Hosted data range from genome assemblies with annotated gene features, transcript and protein expression data to population genetics including variation and insecticide-resistance phenotypes. Here we describe improvements to our resource and the set of tools available for interrogating and accessing BRC data including the integration of Web Apollo to facilitate community annotation and providing Galaxy to support user-based workflows. VectorBase also actively supports our community through hands-on workshops and online tutorials. All information and data are freely available from our website at https://www.vectorbase.org/

Evaluación del triflumurón y la mezcla de Bacillus thuringiensis más Bacillus sphaericus para el control de las formas immaduras de Aedes aegypti y culex quinquefasciatus en sumideros en Cali, Colombia

Introducción. En Cali los sumideros son uno de los principales criaderos de Aedes aegypti y Culex quinquefasciatus que son controlados por la Secretaría de Salud Municipal utilizando el insecticida triflumurón desde 1999. Se sospecha falla al tratamiento. Objetivos. Evaluar la eficacia del Starycide® (triflumurón) y VectoMax® (mezcla bacteriana de Bacillus thuringiensis var. israelensis y Bacillus sphaericus) en el control de A. aegypti y C. quinquefasciatus en los sumideros y determinar el efecto residual de una única aplicación de VectoMax®, en épocas de alta y baja pluviosidad. Materiales y métodos. La eficacia de los productos fue medida en 60 sumideros de una zona residencial de Cali por un período de 90 días. La media de individuos inmaduros (larvas y pupas de A. aegypti y C. quinquefasciatus) fueron obtenidas quincenalmente de 40 sumideros intervenidos (20 con triflumurón y 20 con VectoMax®) y 20 sin tratamiento (grupo testigo). El efecto residual de la mezcla bacteriana se evaluó quincenalmente en 10 sumideros en cada temporada climática. Resultados. Los sumideros tratados con VectoMax® presentaron diferencias en el promedio de estadios inmaduros en ambas especies frente al testigo (p<0,01). En contraste, el tratamiento con triflumurón sólo presentó diferencias en los estadios inmaduros de A. aegypti con respecto al testigo (p<0,001). El efecto residual del VectoMax® fue mayor en la época de baja pluviosidad con respecto al testigo (p<0,001). Conclusión. La mezcla bacteriana fue el tratamiento más eficaz en el control de ambas especies durante el período evaluado (15 días).Introduction. In Cali, Colombia, catch basins (streetside storm drains) are one of the main larval habitats of Aedes aegypti and Culex quinquefasciatus. Since 1999, these mosquitoes have been controlled by the Secretaría de Salud Municipal (Secretary of Municipal Public Health) using the larvicide triflumuron. Because of high densities of these mosquitoes that remain in the city, treatment failure was suspected -possibly insecticide resistance of the target species. Objectives. The efficacy of triflumuron and VectoMax® (biorational mixture of Bacillus thuringiensis var. israelensis plus Bacillus sphaericus) were evaluated in the control of A. aegypti and C. quinquefasciatus in catch basins. The residual effect of a single application of the biorational formulation was determined in catch basins during periods of high and low rainfall. Materials and methods. The efficacy of the products was measured in 60 catch basins located in a residential neighborhood of Cali for a period of 90 days. The mean number of immature instars (A. aegypti and C. quinquefasciatus larvae and pupae of both species) was determined biweekly from 40 catch basins with insecticide intervention (20 treated with triflumuron, 20 with VectoMax®) and 20 untreated (control group). The residual effect of the biorational larvicide was evaluated biweekly in 10 catch basins during each of the 2 climatic periods. Results. The catch basins treated with VectoMax® presented a significantly lower mean number of immature instars of both species compared with the control (p<0.01). In contrast, the triflumuron treatment significantly reduced only immature instars of A. aegypti compared with the control (p<0.001). The residual effect of VectoMax® was higher during low rainfall compared to the control (p<0.001). Conclusion. The biorational formulation was the more effective treatment for the control of both species during the period of evaluation (15 days)

A “Genome-to-Lead” Approach for Insecticide Discovery: Pharmacological Characterization and Screening of <em>Aedes aegypti</em> D₁-like Dopamine Receptors

<div><h3>Background</h3><p>Many neglected tropical infectious diseases affecting humans are transmitted by arthropods such as mosquitoes and ticks. New mode-of-action chemistries are urgently sought to enhance vector management practices in countries where arthropod-borne diseases are endemic, especially where vector populations have acquired widespread resistance to insecticides.</p> <h3>Methodology/Principal Findings</h3><p>We describe a “genome-to-lead” approach for insecticide discovery that incorporates the first reported chemical screen of a G protein-coupled receptor (GPCR) mined from a mosquito genome. A combination of molecular and pharmacological studies was used to functionally characterize two dopamine receptors (<em>Aa</em>DOP1 and <em>Aa</em>DOP2) from the yellow fever mosquito, <em>Aedes aegypti</em>. Sequence analyses indicated that these receptors are orthologous to arthropod D₁-like (Gα_s-coupled) receptors, but share less than 55% amino acid identity in conserved domains with mammalian dopamine receptors. Heterologous expression of <em>Aa</em>DOP1 and <em>Aa</em>DOP2 in HEK293 cells revealed dose-dependent responses to dopamine (EC₅₀: <em>Aa</em>DOP1 = 3.1±1.1 nM; <em>Aa</em>DOP2 = 240±16 nM). Interestingly, only <em>Aa</em>DOP1 exhibited sensitivity to epinephrine (EC₅₀ = 5.8±1.5 nM) and norepinephrine (EC₅₀ = 760±180 nM), while neither receptor was activated by other biogenic amines tested. Differential responses were observed between these receptors regarding their sensitivity to dopamine agonists and antagonists, level of maximal stimulation, and constitutive activity. Subsequently, a chemical library screen was implemented to discover lead chemistries active at <em>Aa</em>DOP2. Fifty-one compounds were identified as “hits,” and follow-up validation assays confirmed the antagonistic effect of selected compounds at <em>Aa</em>DOP2. <em>In vitro</em> comparison studies between <em>Aa</em>DOP2 and the human D₁ dopamine receptor (hD₁) revealed markedly different pharmacological profiles and identified amitriptyline and doxepin as <em>Aa</em>DOP2-selective compounds. In subsequent <em>Ae. aegypti</em> larval bioassays, significant mortality was observed for amitriptyline (93%) and doxepin (72%), confirming these chemistries as “leads” for insecticide discovery.</p> <h3>Conclusions/Significance</h3><p>This research provides a “proof-of-concept” for a novel approach toward insecticide discovery, in which genome sequence data are utilized for functional characterization and chemical compound screening of GPCRs. We provide a pipeline useful for future prioritization, pharmacological characterization, and expanded chemical screening of additional GPCRs in disease-vector arthropods. The differential molecular and pharmacological properties of the mosquito dopamine receptors highlight the potential for the identification of target-specific chemistries for vector-borne disease management, and we report the first study to identify dopamine receptor antagonists with <em>in vivo</em> toxicity toward mosquitoes.</p> </div

Neighbor-joining sequence analysis of <i>Aedes aegypti Aa</i>DOP1 and AaDOP2 and representative biogenic amine receptors.

<p>The deduced amino acid sequences for the mosquito dopamine receptors <i>Aa</i>DOP1 and AaDOP2 and additional receptors for dopamine, muscarinic acetylcholine, octopamine, serotonin, and tyramine from <i>Drosophila melanogaster</i> and <i>Apis mellifera</i>, as well as the human D₁-like and D₂-like dopamine receptors were aligned for use in the analysis. Bootstrap values (100 replicates) are indicated with numbers at supported branches. The outgroup is a <i>D. melanogaster</i> diuretic hormone receptor, a Class B GPCR. Abbreviations: <i>Aa</i> = <i>Ae. aegypti</i>; <i>Is</i> = <i>I. scapularis</i>; <i>Dm</i> = <i>D. melanogaster</i>; <i>Am</i> = <i>A. mellifera</i>; <i>Hs</i> = <i>H. sapiens</i>. Sequences: <i>Is</i>dop1, D₁-like dopamine receptor (ISCW001496); <i>Is</i>dop2, D₁-like dopamine receptor (ISCW008775); <i>Dm</i>D-Dop1, D₁-like dopamine receptor (P41596); <i>Dm</i>DAMB, D₁-like dopamine receptor (DopR99B/DAMB: AAC47161), <i>Dm</i>DD2R, D₂-like dopamine receptor (DD2R-606: AAN15955); <i>Dm</i>Dih, diuretic hormone 44 receptor 1 (NP_610960.1); <i>Dm</i>mAChR, muscarinic acetylcholine receptor (AAA28676); <i>Dm</i>OAMB, octopamine receptor in mushroom bodies, isoform A (NP_732541); DM5HT1A, serotonin receptor 1A, isoform A (NP_476802); <i>Dm</i>Tyr, tyramine receptor (CG7431: NP_650652); <i>Am</i>DOP1, D₁-like dopamine receptor (dopamine receptor, D1, NP_001011595); <i>Am</i>DOP2, D₁-like dopamine receptor (dopamine receptor 2, NP_001011567), <i>Am</i>DOP3, D₂-like dopamine receptor (<i>Am</i>DOP3, NP_001014983); <i>Am</i>mAChR, muscarinic acetylcholine receptor (XP_395760); <i>Am</i>OA1, octopamine receptor (oar, NP_001011565); <i>Am</i>5HT1A, serotonin receptor (5ht-1, NP_001164579); <i>Am</i>Tyr, tyramine receptor (XP_394231); <i>Hs</i>D1, D₁-like dopamine receptor (D(1A), NP_000785); <i>Hs</i>D2,D₂-like dopamine receptor (D(2), NP_000786); <i>Hs</i>D3, D₂-like dopamine receptor (D(3), NP_000787); <i>Hs</i>D4, D₂-like dopamine receptor (D(4), NP_000788); <i>Hs</i>D5, D₁-like dopamine receptor (D(1B)/D5, NP_000789).</p

Confirmation and secondary assays for “hit” antagonists of <i>Aa</i>DOP2 and human D₁ receptor.

<p>Select chemistries and the assay control (SCH23390) were tested in dose-response cAMP assays in the presence of 3 µM dopamine in <i>Aa</i>DOP2- or 100 nM dopamine in hD₁-expressing cells (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001478#pntd-0001478-g005" target="_blank">Figure 5</a>). Compounds with IC₅₀ values ≥10 µM are considered to lack activity at <i>Aa</i>DOP2 and were not tested at hD₁. N.D. = not determined; hD₁ = Human D₁ dopamine receptor.</p