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 ().

A reverse vaccinology approach identified novel recombinant tick proteins with protective efficacy against Rhipicephalus microplus infestation.

The cattle tick, Rhipicephalus microplus, causes significant economic losses to the cattle industry. Tick control is predominately achieved via pesticide applications. However, alternative control methods such as vaccines are needed due to the tick's capacity to quickly develop pesticide resistance and to combat tick-borne diseases.

Australian Marine and Terrestrial -Derived Surugamides, and Synthetic Analogs, and Their Ability to Inhibit (Heartworm) Motility.

A bioassay-guided chemical investigation of a bacterium, sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a () and A2a () as potent inhibitors of (heartworm) microfilaria (mf) motility (EC 0.0013-0.

Mining nematode protein secretomes to explain lifestyle and host specificity.

Parasitic nematodes are highly successful pathogens, inflicting disease on humans, animals and plants. Despite great differences in their life cycles, host preference and transmission modes, these parasites share a common capacity to manipulate their host's immune system. This is at least partly achieved through the release of excretory/secretory proteins, the most well-characterized component of nematode secretomes, that are comprised of functionally diverse molecules.

Identification of anti-horn fly vaccine antigen candidates using a reverse vaccinology approach.

Background: The horn fly, Haematobia irritans irritans, causes significant production losses to the cattle industry. Horn fly control relies on insecticides; however, alternative control methods such as vaccines are needed due to the fly's capacity to quickly develop resistance to insecticides, and the pressure for eco-friendly options.

Methods: We used a reverse vaccinology approach comprising three vaccine prediction and 11 annotation tools to evaluate and rank 79,542 translated open reading frames (ORFs) from the horn fly's transcriptome, and selected 10 transcript ORFs as vaccine candidates for expression in Pichia pastoris.

When Secretomes Meet Anthelmintics: Lessons for Therapeutic Interventions.

Helminth secretomes comprise many potential immunomodulators. The molecular and functional diversity of these entities and their importance at the host-parasite interface have been increasingly recognized. It is now common to hypothesize that parasite-derived molecules (PDMs) are essential mediators used by parasites to establish and remain in their hosts.

Dirofilaria immitis JYD-34 isolate: whole genome analysis.

Background: Macrocyclic lactone (ML) anthelmintics are used for chemoprophylaxis for heartworm infection in dogs and cats. Cases of dogs becoming infected with heartworms, despite apparent compliance to recommended chemoprophylaxis with approved preventives, has led to such cases being considered as suspected lack of efficacy (LOE). Recently, microfilariae collected from a small number of LOE isolates were used as a source of infection of new host dogs and confirmed to have reduced susceptibility to ML in controlled efficacy studies using L3 challenge in dogs.

Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite.

Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc.

Enrichment of reticulocytes from whole blood using aqueous multiphase systems of polymers.

This paper demonstrates the enrichment of reticulocytes by centrifuging whole blood through aqueous multiphase systems (AMPSs)-immiscible phases of solutions of polymers that form step-gradients in density. The interfaces of an AMPS concentrate cells; this concentration facilitates the extraction of blood enriched for reticulocytes. AMPS enrich reticulocytes from blood from both healthy and hemochromatosis donors.

Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans.

The macaque malaria parasite Plasmodium knowlesi has recently emerged as an important zoonosis in Southeast Asia. Infections are typically mild but can cause severe disease, achieving parasite densities similar to fatal Plasmodium falciparum infections. Here we show that a primate-adapted P.

Proteomic profiles of soluble proteins from the esophageal gland in female Meloidogyne incognita.

Meloidogyne incognita can infect multiple plant species. Proteins synthesized in the esophageal glands and secreted through the stylet of plant parasitic nematodes play critical roles in the plant-nematode interactions. Female M.

First analysis of the secretome of the canine heartworm, Dirofilaria immitis.

Background: The characterization of proteins released from filariae is an important step in addressing many of the needs in the diagnosis and treatment of these clinically important parasites, as well as contributing to a clearer understanding of their biology. This report describes findings on the proteins released during in vitro cultivation of adult Dirofilaria immitis , the causative agent of canine and feline heartworm disease. Differences in protein secretion among nematodes in vivo may relate to the ecological niche of each parasite and the pathological changes that they induce.

Macrocyclic lactone anthelmintics: spectrum of activity and mechanism of action.

Macrocyclic lactones (MLs), exemplified by the prototype of the class, ivermectin (IVM), are mainstays of programs for the control of nematode and arthropod parasites and pests. Since their introduction 30 years ago, research has revealed that they act on a family of ligand-gated chloride channels gated by glutamate, which is largely restricted to animals in the phyla Nematoda and Arthropoda. Studies on IVM in model organisms have contributed greatly to our understanding of ML pharmacology, but our understanding of the basis for differences among species and among MLs in potency and spectrum remains far from complete.

Proteomic analysis of excretory-secretory products of Heligmosomoides polygyrus assessed with next-generation sequencing transcriptomic information.

The murine parasite Heligmosomoides polygyrus is a convenient experimental model to study immune responses and pathology associated with gastrointestinal nematode infections. The excretory-secretory products (ESP) produced by this parasite have potent immunomodulatory activity, but the protein(s) responsible has not been defined. Identification of the protein composition of ESP derived from H.

Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi.

Ivermectin (IVM) is a broad-spectrum anthelmintic used in filariasis control programs. By binding to nematode glutamate-gated chloride channels (GluCls), IVM disrupts neurotransmission processes regulated by GluCl activity. IVM treatment of filarial infections is characterized by an initial dramatic drop in the levels of circulating microfilariae, followed by long-term suppression of their production, but the drug has little direct effect on microfilariae in culture at pharmacologically relevant concentrations.

Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products.

Introduction: While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection.