Goondomycins A-H: Carbocyclic -Polyketides from an Australian Pasture with Selective Activity against .

A bioassay-guided chemical investigation of an Australian pasture-soil-derived sp. yielded the rare carbocyclic -polyketide kendomycin () along with a series of new analogues, goondomycins A-H (-), featuring unprecedented carbo/heterocyclic scaffolds and chromophores, with structures assigned by detailed spectroscopic analysis, chemical and biochemical transformations, and biosynthetic considerations. Goondomycins B () and F () are noteworthy in being potent motility inhibitors of heartworm microfilaria (EC 0.

Goondolinones A and B: Terpenyl-quinolin-4(1)-ones from an Australian Volcanic Crater Soil-Derived sp., with Selective Activity against (Heartworm).

A chemical investigation of the Australian pasture soil-derived sp. S4S-00245B09, supported by chemical, bioactivity and cultivation profiling, yielded a new class of terpenyl-quinolin-4(1)-ones, goondolinones A and B ( and ), featuring an unprecedented fused seven-membered ether. Structures were assigned to and on the basis of detailed spectroscopic analysis, including X-ray analysis of , and biosynthetic considerations.

Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived sp.

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm microfilaria and/or the gastrointestinal parasite L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (-), together with the known actinopyrones A () and C ().

Secretory microRNA Profiles of Third- and Fourth-Stage Larvae with Different Macrocyclic Lactone Susceptibility: In Search of Biomarkers for Early Detection of Infection.

The canine heartworm, , is among the most important parasites of dogs in the United States and worldwide, and may cause severe and potentially fatal disease. Current diagnostic recommendations rely on serological detection of an adult female antigen, and visualization of microfilariae in the blood. Therefore, a reliable diagnosis can be only performed approximately six months post-infection.

The Course of Microfilaremia in Experimentally Infected Cats.

As one of the causative agents of lymphatic filariasis in humans, has been established as the laboratory model of choice for studying this infection owing to its viability in small animal hosts, with the domestic cat being significant among these. The usefulness of individual feline infections is highly dependent on the levels of circulating microfilariae in the blood; thus, characterizing the course of microfilaremia benefits our understanding of this model. In -endemic regions, cats are also known reservoirs of infection, and describing microfilaremia in a controlled setting may improve transmission modeling.

Potential Role for Flubendazole in Limiting Filariasis Transmission: Observations of Microfilarial Sensitivity.

Flubendazole (FLBZ) is a potent and efficacious macrofilaricide after parenteral administration. Studies in animal models and one trial in patients infected with revealed that FLBZ elicits minimal effects on microfilariae (mf). Severe complications after ivermectin (IVM) treatment of patients with high microfilaraemia are of great concern.

Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq.

The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate.

The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach.

Background: Lymphatic filariasis and onchocerciasis are disabling and disfiguring neglected tropical diseases of major importance in developing countries. Ivermectin is the drug of choice for mass drug administration programs for the control of onchocerciasis and lymphatic filariasis in areas where the diseases are co-endemic. Although ivermectin paralyzes somatic and pharyngeal muscles in many nematodes, these actions are poorly characterized in adult filariae.

The Effect of In Vitro Cultivation on the Transcriptome of Adult Brugia malayi.

Background: Filarial nematodes cause serious and debilitating infections in human populations of tropical countries, contributing to an entrenched cycle of poverty. Only one human filarial parasite, Brugia malayi, can be maintained in rodents in the laboratory setting. It has been a widely used model organism in experiments that employ culture systems, the impact of which on the worms is unknown.

Assessment of Blood Collection from the Lateral Saphenous Vein for Microfilaria Counts in Mongolian Gerbils (Meriones unguiculatus) Infected with Brugia pahangi.

The NIH guidelines for survival bleeding of mice and rats note that using the retroorbital plexus has a greater potential for complications than do other methods of blood collection and that this procedure should be performed on anesthetized animals. Lateral saphenous vein puncture has a low potential for complications and can be performed without anesthesia. Mongolian gerbils (Meriones unguiculatus) are the preferred rodent model for filarial parasite research.

Detection of circulating parasite-derived microRNAs in filarial infections.

Filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. Applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. As a first step, we investigated the presence of circulating miRNAs released by filarial nematodes into the host bloodstream.

Amblyomma cajennense (Fabricius, 1787) (Acari: Ixodidae), the Cayenne tick: phylogeography and evidence for allopatric speciation.

Background: Amblyomma cajennense F. is one of the best known and studied ticks in the New World because of its very wide distribution, its economical importance as pest of domestic ungulates, and its association with a variety of animal and human pathogens. Recent observations, however, have challenged the taxonomic status of this tick and indicated that intraspecific cryptic speciation might be occurring.