Genome of the Giant Panda Roundworm Illuminates Its Host Shift and Parasitic Adaptation

Baylisascaris schroederi, a roundworm (ascaridoid) parasite specific to the bamboo-feeding giant panda (Ailuropoda melanoleuca), represents a leading cause of mortality in wild giant panda populations. Here, we present a 293-megabase chromosome-level genome assembly of B. schroederi to infer its biology, including host adaptations. Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations, suggesting their potential for transmission and rapid adaptation to new hosts. Genomic and anatomical lines of evidence, including expansion and positive selection of genes related to the cuticle and basal metabolisms, indicate that B. schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism. Additionally, we characterized the secretome of B. schroederi and predicted potential drug and vaccine targets for new control strategies. Overall, this genome resource provides new insights into the host adaptation of B. schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages. Our findings on the unique biology of B. schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.     

Bothriocephalus gadellus n. sp. (Cestoda: Bothriocephalidae) from the beardless codling Gadella imberbis (Vaillant) (Moridae) in the southwestern Gulf of Mexico,with a review of species of Bothriocephalus Rudolphi, 1808 reported from gadiform fishes

Bothriocephalus gadellus n. sp. is described from the intestine of the beardless codling Gadella imberbis (Gadiformes: Moridae) from the southwestern Gulf of Mexico. It resembles B. scorpii, the type-species of Bothriocephalus, and B. manubriformis, the only species of the genus reported from the Gulf of Mexico. B. gadellus n. sp. differs from both species in having four excretory canals on each side of the proglottid (three per side in B. scorpii; two per side anastomosing to form an extensive plexus throughout the medulla in B. manubriformis ), 24-33 testes per proglottid (30-60 in B. scorpii; 60-100 in B. manubriformis), a total length of 31-47 mm (32-950 mm in B. scorpii; 130-1,000 mm in B. manubriformis), and a seminal receptacle and wing-like expansions on each proglottid (absent in B. scorpii and B. manubriformis), as well as lacking two sets of reproductive organs per proglottid (present in B. scorpii) and a vagina with a bulbous sphincter near the opening (present in B. manubriformis). An amendment to the generic diagnosis of Bothriocephalus might be warranted if other species of this genus are found to possess a seminal receptacle. B. gadellus n. sp. appears to be like those species of Bothriocephalus that can utilise two intermediate hosts (copepod and fish). B. ellipticus and B. neglectus are designated as species inquirendae. This is the first report of a cestode from a morid fish in the Gulf of Mexico, and the first report of a parasite from a species of Gadellus.     

Lambertellin system,the mechanism for fungal replacement of Monilinia fructigena with Lambertella corni-maris without competitive inhibition on agar media

The ‘Lambertellin system’ was disclosed which rationally explains the fungal replacement (mycoparasitism) of Monilinia fructigena (M. f., the host) with Lambertella corni-maris (L. corni-maris, the parasite) without competitive inhibition in the simultaneous incubations on agar media. The ‘Lambertellin system’ involves; (a) L. corni-maris secretes nontoxic lambertellols (1, 2) as the diffusible precursors of the authentic responsible substance 3 regardless of existence of the host M. f.; (b) In the absence of the host, the environment around the parasite is kept under neutral condition, and both 1 and 2 are readily transformed into 3; (c) Lambertellin (3) inhibits not only the host but also the parasite. The parasite degrades 3 for detoxification; and (d) Upon the host M. f. approaching closely to the area where the parasite inhabits, the environment around the parasite becomes acidic to stabilize 1 and 2, which gives them a chance to diffuse into the host area. Then these are gradually transformed into 3 to inhibit the host without damaging the parasite. This mechanism also accords with the progress of ‘Natsu-Nenju’ disease on apple fruits, which is known to be a mysterious phyto-disease because of two unique stages of its lifecycle, anamorphic (asexual) and teleomorphic (sexual). The ‘Lambertellin system’ would be categorized as a novel class of alleropathies.     

A critical scanning electron microscope study of the scolex of Bothriocephalus acheilognathi Yamaguti, 1934, with a review of the taxonomic history of the genus Bothriocephalus parasitizing cyprinid fishes

Summary Bothriocephalus specimens from one Ctenopharyngodon idella (O+) were fixed using three different techniques and the scolex morphology was examined using scanning electron microscopy. The scolices were compared with figures of the five species of Bothriocephalus and one species of Schyzocotyle previously described from cyprinid fishes. The taxonomic history of the Bothriocephalus species parasitizing cyprinid fish is reviewed. It is concluded that there is only one Bothriocephalus species parasitizing cyprinid fishes, and that continued use should be made of the name B. acheilognathi Yamaguti, 1934. ac]19840326     

Repurposing human PDE4 inhibitors for neglected tropical diseases: Design,synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors

A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub-micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation.     

Babesia argentina: intraerythrocytic location of babesial antigen extracted from parasite suspensions

Goodger B.V. 1973. Babesia argentina: Intraerythrocytic location of babesial antigen extracted from parasite suspensions. International Journal for Parasitology3:387–391. A crude soluble antigen obtained from a mixture of Babesia argentina parasites and infected erythrocyte stromata has been partly purified and characterized by immunological procedures and its intraerythrocytic site demonstrated by fluorescent antibody techniques. This product contained at least two distinct antigens which were species specific. One had an electrophoretic mobility. similar to serum prealbumin, had little HA activity, and was found in or on the internal rim of the erythrocytic membrane. The other had an electrophoretic mobility similar to serum β₁ globulins, was highly active in HA tests, and was found in granules on the internal stromata of the infected erythrocytes. The evidence suggests that both antigens are produced either from the parasite and are associated closely with erythrocytic components or are produced by digestion of erythrocytic components and represent metabolites of the parasite. In either case the antigenic compounds detected are specific to B. argentina.     

A strategic approach to the synthesis of ferrocene appended chalcone linked triazole allied organosilatranes: Antibacterial,antifungal, antiparasitic and antioxidant studies

A series of ferrocene appended chalcone allied triazole coupled organosilatranes (FCTSa 7–FCTSa 12) were synthesised with the aim of amalgamating the pharmacological action of the constituting moieties into a single molecular scaffold. All the synthesised silatranes were well characterized by various spectroscopic techniques like IR, ¹H NMR, ¹³C NMR and elemental analysis. Organosilatranes were then evaluated for their biological alacrity against bacterial and fungal strains compared with the standard drugs Rifampicin and Amphotericin B respectively. The ferrocene conjugates were found to be only moderately effective against the tested microbes. However, the organosilatranes conceded excellent efficacy against parasite G. lamblia with FCTSa 11 arraying the leading results. On the other hand against another parasite T. vaginalis, FCTSa 8 has emerged as an outstanding composite. Further, Total Antioxidant Assay (TAA) with 2,2′-azino-bis-3-(ethylbenzothiazoline-6-sulphonic acid) revealed FCTSa 10 to be the best claimant for radical scavenging activity. Along these lines, introducing some different substituents in the synthesised hybrids may act as a useful strategy for increasing the biological profile of the drugs.     

Synthesis of thymol-based pyrazolines: An effort to perceive novel potent-antimalarials

A series of thymol based substituted pyrazolines and chalcones was synthesized and evaluated for antimalarial activity, using in-vitro and in-vivo malaria models. All the target compounds (5a-k and 6a-j) were found to be active against human malaria parasite strain Plasmodium falciparum NF54. Among all, compounds 5e and 5f of chalcone series and 6c and 6f of pyrazoline series exhibited prominent antimalarial activity with IC₅₀ less than 3 and 2 μM respectively, while other pyrazolines also significantly inhibited the P. falciparum with IC₅₀ less than 10 μM. The designed pharmacophores were found to be effective against P. falciparum. Compound 6f was found to be able to retard malaria progression in mice. This was evident through decreased parasitemia, increased mean survival time and hemoglobin content in the treated animals. Moreover, 6f was observed as an inhibitor of heme polymerization pathway of the malaria parasite. It also inhibited free heme degradation, which could be possibly responsible for higher reactive oxygen species (ROS) in parasite, thus inhibiting the rapid proliferation of the parasite. In addition to this, compound 6f was found to be non-toxic with a good selectivity index. Based on these observations, the compound 6f could be taken up for further antimalarial lead optimization studies.     

Vitellogenin Underwent Subfunctionalization to Acquire Caste and Behavioral Specific Expression in the Harvester Ant Pogonomyrmex barbatus

The reproductive ground plan hypothesis (RGPH) proposes that the physiological pathways regulating reproduction were co-opted to regulate worker division of labor. Support for this hypothesis in honeybees is provided by studies demonstrating that the reproductive potential of workers, assessed by the levels of vitellogenin (Vg), is linked to task performance. Interestingly, contrary to honeybees that have a single Vg ortholog and potentially fertile nurses, the genome of the harvester ant Pogonomyrmex barbatus harbors two Vg genes (Pb_Vg1 and Pb_Vg2) and nurses produce infertile trophic eggs. P. barbatus, thus, provides a unique model to investigate whether Vg duplication in ants was followed by subfunctionalization to acquire reproductive and non-reproductive functions and whether Vg reproductive function was co-opted to regulate behavior in sterile workers. To investigate these questions, we compared the expression patterns of P. barbatus Vg genes and analyzed the phylogenetic relationships and molecular evolution of Vg genes in ants. qRT-PCRs revealed that Pb_Vg1 is more highly expressed in queens compared to workers and in nurses compared to foragers. By contrast, the level of expression of Pb_Vg2 was higher in foragers than in nurses and queens. Phylogenetic analyses show that a first duplication of the ancestral Vg gene occurred after the divergence between the poneroid and formicoid clades and subsequent duplications occurred in the lineages leading to Solenopsis invicta, Linepithema humile and Acromyrmex echinatior. The initial duplication resulted in two Vg gene subfamilies preferentially expressed in queens and nurses (subfamily A) or in foraging workers (subfamily B). Finally, molecular evolution analyses show that the subfamily A experienced positive selection, while the subfamily B showed overall relaxation of purifying selection. Our results suggest that in P. barbatus the Vg gene underwent subfunctionalization after duplication to acquire caste- and behavior- specific expression associated with reproductive and non-reproductive functions, supporting the validity of the RGPH in ants.     

Betulin derivatives impair Leishmania braziliensis viability and host–parasite interaction

Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50% or IC₅₀, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 μM; (2) compound 26 inhibits parasite growth with an IC₅₀ lower than 1 μM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host–parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite–host cell interaction, as well as being leishmanicidal.     

Alkynamide phthalazinones as a new class of TbrPDEB1 inhibitors (Part 2)

Inhibitors against Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) and B2 (TbrPDEB2) have gained interest as new treatments for human African trypanosomiasis. The recently reported alkynamide tetrahydrophthalazinones, which show submicromolar activities against TbrPDEB1 and anti-T. brucei activity, have been used as starting point for the discovery of new TbrPDEB1 inhibitors. Structure-based design indicated that the alkynamide-nitrogen atom can be readily decorated, leading to the discovery of 37, a potent TbrPDEB1 inhibitor with submicromolar activities against T. brucei parasites. Furthermore, 37 is more potent against TbrPDEB1 than hPDE4 and shows no cytotoxicity on human MRC-5 cells. The crystal structures of the catalytic domain of TbrPDEB1 co-crystalized with several different alkynamides show a bidentate interaction with key-residue Gln874, but no interaction with the parasite-specific P-pocket, despite being (uniquely) a more potent inhibitor for the parasite PDE. Incubation of blood stream form trypanosomes by 37 increases intracellular cAMP levels and results in the distortion of the cell cycle and cell death, validating phosphodiesterase inhibition as mode of action.     

Developmental arrest of Haemonchus contortus in sheep treated with a corticosteroid

Adams D. B. 1986. Developmental arrest of Haemonchus contortus in sheep treated with a corticosteroid. International Journal for Parasitology16: 659–664. Developmental arrest of the nematode, Haemonchus contortus, at the fourth larval stage within sheep appears to be controlled by a complex of signals and events in which both host-associated and parasite-associated factors are essential participants. Treatment of worm-free sheep with the corticosteroid, dexamethasone, during infection demonstrated the existence of an arrest-prone state in infective larvae and a host-associated influence actuating the phenomenon of arrest. Not all subpopulations of the parasite responded to the influence of dexamethasone and a selection experiment in which the parasite was passaged through immune and non-immune sheep showed that the arrest-prone state was largely determined by genetic factors. The host-associated factor initiating or actuating arrest and identified by dexamethasone-treatment could be ascribed more satisfactorily to a manifestation of immune responsiveness than to a direct effect of the corticosteroid.     

Antiplasmodial and antimycobacterial cyclopeptide alkaloids from the root of Ziziphus mauritiana

Investigation of the MeOH extract obtained from the root of the Ziziphus mauritiana grown in Thailand resulted in the isolation of two 14- and 13-membered cyclic alkaloids, mauritine L (1) and mauritine M (2), and three known cyclopeptide alkaloids, nummularines H (3), B (4) and hemsine A (5). Their structures were elucidated on the basis of extensive NMR spectroscopic analysis. The first single crystal X-ray diffraction study of the 13-membered ring cyclopeptide, nummularine B methiodide (4′), revealed all S configurations on the amino acid residues. The isolated alkaloids exhibited potent antiplasmodial activity against the parasite Plasmodium falciparum with the inhibitory concentration (IC₅₀) ranging from 3.7 to 10.3 μM. Compounds 2 and 3 also demonstrated antimycobacterial activity against Mycobacterium tuberculosis with the MIC of 72.8 and 4.5 μM, respectively.     

Metal compounds for the treatment of parasitic diseases

The cysteine proteases of the trypanosomatid parasitic protozoa have been validated as targets for chemotherapy of Chagas’ disease and leishmaniasis. Metal complexes of gold, platinum, iridium, palladium, rhodium and osmium have been reported to have activity against a variety of trypanosomatids, but the molecular target of these compounds has not been defined. The activity of gold(III) and palladium(II) cyclometallated complexes, and oxorhenium(V) complexes against mammalian and parasitic cysteine proteases was investigated. All gold(III) complexes (1-6) inhibited cathepsin B with IC₅₀ values in the range of 0.2-1.4 μM. Of the six palladium compounds, aceto[2,6-bis[(butylthio-κS)methyl]phenyl-κC]-, (SP-4-3)-palladium(II) (11) was the most potent inhibitor of cathepsin B with an IC₅₀ of 0.4 μM. A clear structure-activity relationship was observed with the oxorhenium(V) complexes with chloro[2,2′-(thio-κS)bis[ethanethiolato-κS)]] oxorhenium(V) (16) being the most potent inhibitor of cathepsin B with an IC₅₀ of 0.009 μM. Six complexes were further tested against the parasite cysteine proteases, cruzain from T. cruzi, and cpB from L. major; the most potent inhibitors were the two rhenium complexes (2(1H)-pyridinethionato-κS²)[2,6-bis[(mercapto-κS)methyl]pyridine-κN¹] oxorhenium(V) (15) and chloro[2,2′-(thio-κS)bis[ethanethiolato-κS)]] oxorhenium(V) (16). The compounds were also evaluated in assays for parasite growth. Two oxorhenium(V) compounds ((p-methoxyphenylthiolato-S)[2,6-bis[(mercapto-κS)methyl]pyridine-κN¹] oxorhenium(V) (14) and (methanethiolato)[2,2′-(thio-κS)bis[ethanethiolato-κS)]] oxorhenium (V) (18)) and the palladium compound 11 inhibited T. cruzi intracellular growth, and compound 11 inhibited promastigote growth in three Leishmania species. In conclusion this preliminary data indicates that metal complexes targeted at parasite cysteine proteases show promise for the treatment of both Chagas’ disease and leishmaniasis.     

Complex foraging ecology of the red harvester ant and its effect on the soil seed bank

Granivory is an important interaction in the arid and semi-arid zones of the world, since seeds form an abundant and nutritious resource in these areas. While species of the genus Pogonomyrmex have been studied in detail as seed predators, their impact on seed abundance in the soil has not yet been explored in sufficient depth. We studied the impact of the harvesting activities of the ant Pogonomyrmex barbatus on seed abundance in the soil of the Zapotitlán valley, Mexico. We found that P. barbatus activity significantly impacts the abundance of seeds in the soil, which is lower in the sites where P. barbatus forages than it is in sites with no recorded foraging. We also found that P. barbatus distributes intact seeds of three tree species, two of which are nurse plants, and could consequently be promoting the establishment of these species. Using tools derived from graph theory, we observed that the ant-seed interactions exhibit a nested pattern; where more depredated seed species seem to be the more spatially abundant in the environment. This study illustrates the complex foraging ecology of the harvester ant P. barbatus and elucidates its effect on the soil seed bank in a semi-arid environment.     

Microhabitats of gill parasites (Monogenea and copepoda) of teleosts (Scomberoides spp.)

Ramasamy P., Ramalingam K., Hanna R. E. B. and Halton D. W. 1985. Microhabitat of gill parasites (Monogenea and Copepoda) of teleosts (Scomberoides spp.). International Journal for Parasitology15: 385–397. The parasites Vallisia indica, Allodiscocotyla chorinemi, Heterapta chorinemi, and Dionchus remorae exhibited site specificity on the gills of Scomberoides commersonianus, S. tol, S. lysan and S. tala, whereas the copepod Caligus sp. did not. Observations on site preference revealed microhabitat differences along the length of gill filaments, along the anterio-posterior axis of the gill, between external and internal gill filaments and on different gill arches. Site preference varied with parasite density on each gill and host. An interspecific association test between pairs of species revealed, in some cases, a positive association, and in other cases a negative association. There were apparently no association? between certain pairs of species. A comparison of intensity within pairs of parasite species infecting the same host revealed either an inverse or a direct correlation. The numerical dominance and prevalence of parasites differed on each host species. This study indicates that intra- and interspecific competition may occur among the gill parasites. The direction and speed of ventilation water-currents and certain intrinsic factors of the parasite themselves may determine their microhabitat restriction on the gills.     

Phylogenetic relationships among four species and a sub-species of Mullidae (Actinopterygii; Perciformes) based on mitochondrial cytochrome B, 12S rRNA and cytochrome oxidase II genes

DNA sequence comparisons of three mitochondrial DNA genes were used to reveal phylogenetic relationships among four species and a sub-species of Mullidae family. This is the first report using mitochondrial DNA sequence data to infer intraspecific relationship among different populations of Mullus barbatus and Mullus surmuletus; phylogenetic relationships between M. barbatus and its sub-species; M. barbatus ponticus. Cytochrome b, 12S ribosomal RNA, and cytochrome oxidase II regions of 242 individuals belonging to species M. barbatus, M. surmuletus, Upeneus moluccensis, Upeneus pori and sub-species M. barbatus ponticus were sequenced and phylogenetic trees were constructed using four different algorithms. The phylogenetic trees constructed support the existing taxonomical data of two mullid genera (Mullus, Upeneus). Molecular data shows no significant difference between same species of different geographical populations. The results suggest that the molecular difference is not large enough between M. barbatus and M. barbatus ponticus to consider them as sub-species.     

Synthesis and evaluation of analogs of the phenylpyridazinone NPD-001 as potent trypanosomal TbrPDEB1 phosphodiesterase inhibitors and in vitro trypanocidals

Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. Knock down of both enzymes leads to cell cycle arrest and is lethal to the parasite. Recently, we reported the phenylpyridazinone, NPD-001, with low nanomolar IC₅₀ values on both TbrPDEB1 (IC₅₀: 4 nM) and TbrPDEB2 (IC₅₀: 3 nM) (J. Infect. Dis. 2012, 206, 229). In this study, we now report on the first structure activity relationships of a series of phenylpyridazinone analogs as TbrPDEB1 inhibitors. A selection of compounds was also shown to be anti-parasitic. Importantly, a good correlation between TbrPDEB1 IC₅₀ and EC₅₀ against the whole parasite was observed. Preliminary analysis of the SAR of selected compounds on TbrPDEB1 and human PDEs shows large differences which shows the potential for obtaining parasite selective PDE inhibitors. The results of these studies support the pharmacological validation of the Trypanosome PDEB family as novel therapeutic approach for HAT and provide as well valuable information for the design of potent TbrPDEB1 inhibitors that could be used for the treatment of this disease.     

Studies on parasitic castration: Occurrence of a gametogenesis-inhibiting factor in extract of Zoogonus lasius (Trematoda)

Testes of nonparasitized Ilyanassa obsoleta were maintained in vitro in a modification of the medium originally devised by Burch and Cuadros [Nature (London)206, 637–638 (1965)] in order to ascertain whether a saline extract of the daughter sporocysts of Zoogonus lasius would cause the inhibition of spermatogenesis. This parasite is known to cause parasitic castration of I. obsoleta in nature. It has been ascertained that after 96 hr of incubation with the parasite extract the incorporation of [³H]thymidine is inhibited in some spermatogonia. This represents the first experimental evidence that some molecule(s) of parasite origin may be responsible for chemical parasitic castration.