In silico prediction and in vitro assessment of novel heterocyclics with antimalarial activity.

The development of new antimalarials is paramount to keep the goals on reduction of malaria cases in endemic regions. The search for quality hits has been challenging as many inhibitory molecules may not progress to the next development stage. The aim of this work was to screen an in-house library of heterocyclic compounds (HCUV) for antimalarial activity combining computational predictions and phenotypic techniques to find quality hits. The physicochemical determinants, pharmacokinetic properties (ADME), and drug-likeness of HCUV were evaluated in silico, and compounds were selected for structure-based virtual screening and in vitro analysis. Seven Plasmodium target proteins were selected from the DrugBank Database, and ligands and receptors were processed using UCSF Chimera and Open Babel before being subjected to docking using Autodock Vina and Autodock 4. Growth inhibition of P. falciparum (3D7) cultures was tested by SYBR Green assays, and toxicity was assessed using hemolytic activity tests and the Galleria mellonella in vivo model. From a total of 792 compounds, 341 with good ADME properties, drug-likeness, and no interference structures were subjected to in vitro analysis. Eight compounds showed IC50 ranging from 0.175 to 0.990 µM, and active compounds included pyridyl-diaminopyrimido-diazepines, pyridyl-N-acetyl- and pyridyl-N-phenyl-pyrazoline derivatives. The most potent compound (UV802, IC50 0.178 µM) showed no toxicophoric and was predicted to interact with P. falciparum 1-cysperoxidredoxin (PfPrx1). For the remaining 7 hits (IC50 < 1 µM), 3 showed in silico binding to PfPrx1, one was predicted to bind the haloacid dehalogenase-like hydrolase and plasmepsin II, and one interacted with the plasmodial heat shock protein 90.

Pathogenesis and in vivo interactions of human Streptococcus agalactiae isolates in the Galleria mellonella invertebrate model.

Group B Streptococcus (GBS) is a gram positive bacterium colonizing the gastrointestinal and urogenital tracts in humans. However under certain conditions GBS invades leading to severe infections in neonates, pregnant women, immunocompromised patients and the elderly people. The precise mechanisms involved in the transition from colonizer to pathogen remain to be elucidated, however it has been suggested that environmental determinants may regulate gene expression resulting in GBS invasion. We have assessed the potential of the moth Galleria mellonella as a model to study the in vivo virulence and GBS interactions of invasive and noninvasive human isolates from our population. Temperature, pH and bacterial competition effects were examined in the model as well as the response of Galleria hemocytes to GBS infection. GBS strains were able to effectively grow and infect G. mellonella in a dose dependent manner with a (half-lethal dose) LD50 1 × 107 CFU after 24 h. GBS infection induced larva melanization with hemocyte vacuolation and depletion. Larval killing increased with environmental conditions such as temperature (37 °C) and pH (≥5.5-7.2). Bacterial interference assays showed a remarkable antagonistic effect of Lactobacillus gasseri (cells and filtrates) on GBS infection and significantly improved Galleria survival. The protective effect of L. gasseri was observed even at ratios similar to those of GBS colonization suggesting that L. gasseri modulation by its metabolic products is relevant. Exposure to L. gasseri acidic filtrates induced growth inhibition and prevented larva killing after infection with the hypervirulent GBS clone (a multiresistant clinical ST 17 strain). We showed that mechanisms mediating these effects are mainly pH dependent, however other mechanisms may have a role depending on inocula. We also found that G. mellonella infected with invasive human GBS isolates showed differential killing curves with higher killing rates after 24 h when compared to those considered colonizers or noninvasive isolates. Overall it has been shown that G. mellonella may be a representative in vivo model for baseline GBS studies. Given the potential effects over the hypervirulent strain, our findings support the use of L. gasseri in the GBS control strategies based on Lactobacillus formulations.

HALLAZGOS NUEVOS EN LA DISTRIBUCIÓN GEOGRÁFICA DE WarileyaY Brumptomyia(DIPTERA: PSYCHODIDAE) EN EL SUROESTE DE COLOMBIA / New Geographic Records of Warileyaand Brumptomyia (Diptera: Psychodidae) in South Western Colombia

Se informa la presencia de Warileya nigrossaculus y Warileya rotundipennis en nuevas localidades de Buenaventura, y se registra por primera vez Brumptomyia beaupertuyi para el occidente de Colombia, en una zona rural de Tuluá, Valle del Cauca, Colombia.

The presence of Warileya nigrossaculus and Warileya rotundipennis is informed in new localities of Buenaventura. Brumptomyia beaupertuyi is registered for the first time in western Colombia, in a rural area of Tuluá, Valle del Cauca, Colombia.

Registros de lutzomyia (Diptera: Psychodidae) en nuevas localidades de Colombia / Records of lutzomyia (Diptera: Psychodidae) in new localities of Colombia

Introducción: Los insectos del género Lutzomyia son vectores biológicos de bacterias, protozoarios y virus que atacan tanto a los seres humanos como a los animales. Tienen importancia sobre todo por cuanto las hembras, que son hematófagas, transmiten las diversas formas de leishmaniasis. En Colombia diferentes estudios han comunicado la distribución geográfica de estos dípteros. Con el presente trabajo se informan las especies en distintas localidades y se incluyen varios lugares sin registros conocidos antes. Materiales y métodos: Los ejemplares de este estudio se capturaron cuando pretendían picar a los colectores y con trampas donde el cebo era la luz o un animal. Varios especimenes se atraparon en sitios de reposo. A los flebótomos así obtenidos se les trató con diversos sistemas para poder disecarlos y montarlos entre lámina y laminilla a fin de hacer las identificaciones hasta especie. Resultados: A partir del estudio de 716 representantes, 124 machos y 592 hembras del género Lutzomyia, en 46 sitios de 29 municipios, 11 departamentos, fue posible identificar 33 especies. Discusión: Se amplía en forma considerable la distribución geográfica de los miembros del género Lutzomyia en varios sitios de Colombia. Se menciona la importancia de algunas especies antropofílicas en su responsabilidad como transmisores de enfermedades, sobre todo de las distintas leishmaniasis y se destaca la necesidad de estudios sistemáticos y taxonómicos a fin de fijar sus papeles en la diseminación de agentes patógenos que afectan a los seres humanos.

Introduction: Phlebotomine sand flies are biological vectors of bacteria, protozoa and viruses attacking both human beings and animals. Sand flies are important since females have haematophagous habits and transmit various types of leishmaniases. In Colombia different studies have given the geographic distribution of these insects. This paper reports the finding of species in several localities and includes some places with no previous records. Material and methods: Specimens were captured while attempting to bite on collectors and with traps (light bait and animal bait). Other specimens were trapped in resting places. Sand flies were processed with different techniques regularly used for dissecting and mounting them for species identification. Results: From the study of 716 specimens, 124 males and 592 females, of the genus Lutzomyia in 46 places from 29 municipalities, in 11 departments (= states, provinces) it was possible to identify 33 species. Discussion: The geographic distribution of the genus Lutzomyia is being greatly extended to new Colombian localities. The importance of some anthropophilic species as vectors of diseases, mainly leishmaniases is discussed. The necessity of systematic and taxonomic studies to know the role of these insects in the transmission of pathologies affecting humans is emphasized.

Description of Lutzomyia (Trichophoromyia) pabloi n. sp. and the female of L. howardi (Diptera: Psychodidae) from Colombia.

A new Lutzomyia species in the subgenus Trichophoromyia, L. pabloi, is described and illustrated. A description of the previously unknown female of L. howardi Young is also presented. These specimens were captured in the Amazon region of Colombia.

Flies (Calliphoridae, Muscidae) and beetles (Silphidae) from human cadavers in Cali, Colombia.

Adult specimens of Cochliomyia macellaria, Chrysomya megacephala, Ch. rufifacies, Lucilia sp. (Calliphoridae), Musca domestica (Muscidae), Oxelytrum discicolle (Silphidae) and Sarcophagidae were recovered from 12 human cadavers in Cali, Valle, Colombia. Information regarding these findings is presented.

Flies (Calliphoridae, Muscidae) and Beetles (Silphidae) from human cadavers in Cali, Colombia

Adult specimens of Cochliomyia macellaria, Chrysomya megacephala, Ch. rufifacies, Lucilia sp. (Calliphoridae), Musca domestica (Muscidae), Oxelytrum discicolle (Silphidae) and Sarcophagidae were recovered from 12 human cadavers in Cali, Valle, Colombia. Information regarding these findings is presented

Lutzomyia sand flies (Diptera: Psychodidae) from middle and lower Putumayo Department, Colombia, with new records to the country

A total of 4,840 phlebotomine sand flies from 54 localities in Putumayo department (=state), in the Colombian Amazon region, were collected in Shannon traps, CDC light traps, resting places and from human baits. At least 42 Lutzomyia species were registered for the first time to the department. Psychodopygus and Nyssomyia were the subgenera with the greatest number of taxa, the most common species being L. (N.) yuilli and L. (N.) pajoti. They were sympatric in a wide zone of Putumayo, indicating that they should be treated as full species (new status). Among the anthropophilic sand flies, L. gomezi and L. yuilli were found in intradomiciliar, peridomestic, urban or forest habitats. L. richardwardi, L. claustrei, L. nocticola and L. micropyga are reported for the first time in the Colombian Amazon basin. L. pajoti, L. sipani and L. yucumensis are new records for Colombia.