Parasitism Capacity Research Articles

Response of Trichogramma spp. (Hymenoptera: Trichogrammatidae) to Insecticides at Concentrations Sublethal to Cnaphalocrocis medinalis (Lepidoptera: Pyralidae).

Trichogramma japonicum Ashmead (Hymenoptera: Trichogrammatidae) and Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) are important parasitoids of Lepidopteran pests and are used for biological control in rice fields. In this study, the response of two of these parasitoids to four insecticides (chlorpyrifos, chlorantraniliprole, emamectin benzoate, and spinosad) were evaluated at target sublethal concentrations (TSC10 and TSC25, representing the LC10 and LC25 to the target pest) of the important rice pest, Cnaphalocrocis medinalis (Guenée). Each of the insecticides led to the mortality of adult T. japonicum and T. dendrolimi at TSC10 and TSC25, whereas no significant differences in the mortality of T. japonicum between TSC10 of chlorantraniliprole and control groups occurred. The parasitic capacity increased at F0 of T. japonicum at the two TSCs of spinosad treated host eggs, whereas the TSC10 was lower for emamectin benzoate at F1 for T. japonicum. The TSCs of chlorpyrifos treated host eggs negatively influenced the emergence rates of T. japonicum at F1. Emamectin benzoate with TSC10 reduced the female ratio of T. japonicum at F1. For T. dendrolimi, the TSCs of chlorpyrifos treated host eggs negatively influenced the emergence rates at F1. These findings indicate that T. japonicum and T. dendrolimi are affected by insecticides at TSCs, and among the four insecticides, chlorantraniliprole had the lowest mortality rates for T. japonicum and T. dendrolimi at TSCs.

Fast Automatic Tuning of a Synthetic Inductor for Automotive Transformer-Less Ultrasonic Sensor in Park Assist Systems

This paper presents a novel shunt tuning method suitable for transformer-less ultrasonic sensors in park assist systems. The method enables tuning of an inductive part of LR shunt that is used for a transducer damping. The method relies on the knowledge of a transducer own serial resonance frequency and the measurement of a parallel resonance frequency, which corresponds to the transducer parasitic capacity and shunt inductance. From the ratio of these two resonance frequencies, the method predicts how the inductance must be tuned to achieve optimal damping performance. To enable measurement of the parallel resonance frequency inductance scaling by a factor of four is employed. The scaled inductance shifts the parallel resonance frequency away from the serial resonance frequency and thus distinguishes them. This paper is supported by practical experiments using a fabricated test chip with a tunable synthetic inductor that confirms its performance and shows improvements compared to previous solutions without adaptive tuning mechanisms.

Effects of Extrinsic, Intraspecific Competition and Host Deprivation on the Biology of Trichopria anastrephae (Hymenoptera: Diapriidae) Reared on Drosophila suzukii (Diptera: Drosophilidae).

The pupal parasitoid Trichopria anastrephae Lima (Hymenoptera: Diapriidae) shows potential to control Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), and understanding the behavior of this parasitoid in challenging environments is important to obtain a higher efficiency in mass rearing and in biological control programs. This study aimed to verify the effects of extrinsic intraspecific competition and the absence of host on the parasitism of T. anastrephae in D. suzukii pupae. Therefore, to evaluate the parasitism of T. anastrephae under intraspecific competition, groups of 20 pupae (24h old) of D. suzukii were offered for different densities of parasitoids (1, 3, 5, or 10 couples) during a 7-day period. Whereas to evaluate the effects of host deprivation on parasitism of T. anastrephae, we tested different treatments: T1-no deprivation, T2-complete deprivation, T3-deprivation every other day, T4-deprivation for 3days, and T5-deprivation for 7days. The increase of density of parasitoids resulted in an increase of oviposition scars on pupae and a longer biological cycle, suggesting the occurrence of superparasitism. Increased density also resulted in a higher percentage of attacked pupae, but did not affect parasitoids emergence nor sex ratio. Host deprivation affected number of parasitized pupae, number and sex ratio of offspring, and the longevity of females. Based on our findings, competition among females do not impair offspring viability, and host deprivation for a period up to 7days do not influence parasitism capacity, indicating that it can be used as a pre-release strategy.

Capacity for Parasitism of Trichogramma spp. in Tomato Fruit Borer under Different Temperatures

The parasitoid in eggs of Trichogramma genre is the most studied in the world, being bred widely and used for flooding releases. This study aimed to evaluate the capacity for parasitism of Trichogramma galloi Zucchi, 1988 (Hymenoptera: Trichogrammatidae) in Neoleucinodes elegantalis (Guenée) (Lepidoptera: Crambidae) eggs at different temperatures. The experiment was developed at the Nucleus for Scientific and Technological Development in Phytosanitary Management (NUDEMAFI) in which the daily and accumulated biological parameters were assessed, as well as total parasitized eggs by female, sexual ratio (number of females/number of males + females), viability of the eggs (number of eggs with orifice/number of parasitized eggs x 100) and number of individuals per egg at temperatures 18, 21, 24, 27 and 30ºC. The eggs of the fruit borer were offered daily to each T. galloi female at each temperature until the death of the parasitoid could be verified. The larger number of parasitized eggs was found in the first 24 h, at temperatures 24 and 27ºC with 17 parasitized eggs. The accumulated parasitism in N. elegantalis eggs reached 80% of total parasitized eggs for each thermal range (18, 21, 24, 27 and 30ºC) on the 2nd, 3rd, 3rd, 1st and 2nd days respectively. The ideal parasitism conditions for this lineage vary between 24 and 27°C. Therefore, it is concluded that the studied T. galloi lineage has adequate biological parameters in N. elegantalis eggs, demonstrating promise in phytosanitary management of this pest.

Host performance of Trichogramma species on Opisina arenosella, and evaluation of their biological control efficacy

Abstract Five candidate species for biocontrol of Opisina arenosella Walker, a destructive pest of palm trees, were evaluated. To compare host performance, 5 Trichogramma species were allowed to parasitize O. arenosella eggs of different ages and egg densities. The parasitization capacity of two species, T. embryophagum and T. japonicum, were evaluated with respect to adult age. Treatments consisted of field with releases of T. embryophagum or T. japonicum set up in Danzhou, Hainan, and the pest densities was recorded periodically. The results showed that T. embryophagum, T. chilonis, and T. dendrolimi had a strong parasitic ability on 0-day-old O. arenosella eggs. In species comparisons, the parasitism rates of T. embryophagum on 1-day-old and 4-day-old eggs, and T. japonicum on 2-day-old, 3-day-old, and 5-day-old eggs of O. arenosella were significantly higher than those of other Trichogramma species. At densities of 40 and 35 eggs/tube (84.8 cm3), the numbers of eggs parasitized by T. embryophagum and T. japonicum were the highest, at 29.9 and 24.6, respectively. During the first 24-h, the numbers of eggs parasitized by T. embryophagum and T. japonicum were 110.6 and 82.2, accounting for 84.7% and 59.5%, respectively, of the total parasitized eggs. After 2 months releases, the larvae and pupa density of O. arenosella under T. embryophagum and T. japonicun treatment were 0.95 and 0.94 individuals/leaflet, respectively, were significantly lower than untreated control (1.6 individuals/leaflet). These findings encouraged that T. embryophagum and T. japonicun are able to be used for biological control for O. arenosella.

Overwintering of reproductively mature females of a pro‐ovigenic parasitic wasp, Leptopilina heterotoma (Hymenoptera: Figitidae)

AbstractLeptopilina heterotoma is a Drosophila parasitoid mainly occurring in temperate regions, and females of this species are pro‐ovigenic (i.e. all or nearly all of their lifetime eggs are already mature at emergence). Here I investigated how L. heterotoma overwinters in Sapporo, Japan, a cool temperate region, by outdoor and laboratory experiments. Females of this species had mature eggs at emergence as expected, and they did not resorb eggs even if they were exposed to cold or starvation. Nevertheless, females were able to overwinter, and post‐overwintering females retained parasitization capacity. In this species, thus, adult overwintering is not associated with reproductive diapause. However, females grown in late autumn or at low temperatures (e.g. 5°C) had a fewer number of mature eggs and higher winter survival. At low temperatures, female larvae could save energy by reducing egg production and allocate the saved energy to expenditure for overwintering. In contrast to females, males and pre‐adult individuals were not able to overwinter.

The method of processing the droplet-air flow by non-equilibrium plasma

The paper considers a fundamentally new installation for the processing of a droplet-air environment in a non-equilibrium plasma. Its various designs are presented. This installation is built on the basis of pulsed energy devices and is intended for water disinfection and decomposition of dissolved organic compounds, the production of nanomaterials, research in physics and chemistry, etc. We have conducted research of the performance and energy efficiency of this method of processing. It is established that in obtaining the target product, this method of processing has an advantage over the known methods: due to high performance and energy efficiency, as well as the simplicity of this processing method. In addition, the parasitic load capacity of the nanosecond generator is reduced several times, this fact increases the voltage rise rate on the cells of the plasma plasmatrons, which improves performance and energy efficiency.

Does Diachasmimorpha longicaudata (Hymenoptera: Braconidae) have a preferential instar to parasitize Tephritidae (Diptera)?

ABSTRACT Diachasmimorpha longicaudata (Ashmead, 1905) is a koinobiont parasitoid of Tephritidae larvae, the third instar larvae of which is considered preferential, but it is able to parasitize other larval stages and compete with native parasitoids. This study investigated the preference and parasitism capacity of D. longicaudata in larvae of different instar of Anastrepha fraterculus (Wiedemann, 1830) (AF) and Ceratitis capitata (Wiedemann, 1824) (CC). The experiments were carried out under laboratory conditions, one instar being offered at a time in parasitism units, with the following choices among the hosts: 25 AF larvae and 25 CC larvae (first, second and third instar were evaluated). The other test was a multiple-choice in relation to the instar, for larvae of the same host species, with three parasitism units being offered, with 15 larvae of each instar. The mean number of formed pupae, emerged parasitoids, parasitized pupae, unviable pupae and sex ratio were evaluated. In the first bioassay, the mean number of emerged parasitoids and parasitized pupae in the AF host were significantly higher in treatments with first and second instar larvae. For CC there was no difference between the instars tested. In the second bioassay, the mean value of emerged parasitoids and parasitized pupae, was higher in second and third instar larvae for CC, and for AF was in second instar larvae. The sex ratio was biased for males in all treatments in both bioassays. The results show that D. longicaudata can parasitize and be successful in all available larval instars, being able to compete with parasitoids of any instar.

Growing Trend in Application of Age-Stage, Two-Sex Life Table Theory in Diverse Ecological and Pest Management Studies

Life table is an effective tool for characterizing the demography of an arthropod to understand the phenomenon in pest population development which is a key for developing IPM strategy. Age-stage, two-sex life tables provide comprehensive insights into the stage differentiation of an arthropods, compared with the traditional female age-specific life tables and any other forms of life tables. The age-stage, two-sex life table approach is applied in diverse type of ecological and pest management research. This article is intended to draw attention of Nepalese researchers towards the significance of demographic studies for development of IPM strategy, advancements in application of age-stage, two-sex life table approach and its computer programs. Altogether more than 694 peer reviewed papers and PhD theses have been published since 1988. Out of this, 92 papers were sampled and reviewed for this paper. In such papers, demography of diverse 50 species of arthropods classified under 27 different families belonging to 10 orders have been studied using this theory to measure their fitness in diverse food and environment condition, to assess their consumption, predation or parasitism capacity and to project their population growth in different scenario, to forecast the timing of control based on the stage structure of pest populations and to be used in mass rearing and harvesting of predators and preys under biological control program.

Effect of Sublethal Doses of Imidacloprid on the Biological Performance of Aphid Endoparasitoid Aphidius gifuensis (Hymenoptera: Aphidiidae) and Influence on Its Related Gene Expression.

The integrated pest management (IPM) strategy was developed and used in combination with pesticides and beneficial biological control agents. To further develop IPM efficiency, it is important to evaluate the side effects of pesticides on biological control agents. Aphidius gifuensis is one of the most important aphid natural enemies and has been successfully used to control Myzys persicae and other aphid species. Imidacloprid (IMD) is a popular pesticide used worldwide and is highly toxic to non-target arthropods. Here, we investigated the short-term sublethal toxicity of IMD in Aphidius gifuensis and its impact on the biological performance and gene expression of this parasitoid. We found that sublethal IMD doses had a significant negative effect on the life history traits of female A. gifuensis, including shortening the lifespan and lowering parasitic capacity. Moreover, exposure to sublethal IMD also adversely affected the response of A. gifuensis to aphid-infested plant volatiles. Based on the transcriptome analysis, we found that the exposure to sublethal IMD doses significantly affected expression of genes involved in the central nervous system, energy metabolism, olfactory, and detoxification system of A. gifuensis. RT-qPCR also revealed that short term expose to sublethal IMD doses significantly induced the gene expression of genes related to the central nervous system (nAChRa7, nAChRa9, TbH, OAR1, NFR, TYR, and DAR1), olfactory system (OR28 and IR8a1), and detoxification system (CYP49p3, CYP6a2, and POD), while it suppressed the expression of genes involved in the central nervous system (nAChRa4 and nAChRb1), olfactory system (Orco1, IR8a2, and GR1), and detoxification system (GST2). Furthermore, exposure to sublethal doses of IMD also significantly increased the activities of CarEs and POD, whereas we observed no influence on the activities of CAT, GST, and SOD. Our results indicate that sublethal IMD doses might adversely affect the biological performance of A. gifuensis by altering gene expression related to the function of olfactory, nervous, energy metabolism, and detoxification systems. Thus, how the use of pesticides directly affect insect population should be considered when used in conjunction with natural pest parasitoids in IPM strategies.

Host-preference and parasitic capacity of new candidates of Trichogramma species (Hym.:Trichogrammatidae) against some stored product moths

The host-preference and parasitic capacity of some local Trichogramma spp. (T. bourarachae, T. cordubensis, T. euproctidis and T. cacociae) towards four species of stored product moth eggs were investigated in order to select new candidate species for use in mass rearing and biological control against moths in storages. The efficacy of the Trichogramma spp. was compared with T. evanescens, the common wasp used commercially for biological control. Experiments were carried out by offering a single parasitoid female to eggs of the Indianmeal moth Plodia interpunctella (Hubner), the Mediterranean flour moth Ephestia kuehniella Zeller, the warehouse moth E. elutella (Hubner), and the almond moth, Cadra cautella (Walker) in choice and no-choice assays. Two different choice experiments were used to certify the same conclusion in both methods. The bioassay for host-preference of Trichogramma was carried out by offering a single early female wasp the choice between equal numbers of host eggs on square cards “Petri dish tests “and/or strip cards “strip card tests”. In Petri dish tests, E.kuehniella was a highly acceptable host species for T. bourarachae, T. euproctidis, and T. cacociae wasps while E.elutella and C.cautella eggs were more acceptable for T. evanescens and T.cordubensis, respectively. In strip card tests, E.kuehniella eggs were highly acceptable for T.bourarachae, T.cacociae and T.evanescens. Eggs of E.elutella and C.cautella were more acceptable for T.euproctidis andT. cordubensis, respectively. Significant differences were found among the parasitic capacity of the tested Trichogramma spp.: T. borarachae showed a good parasitic potential against S.cerealella and E. kuehniella; T.evanescens and T. cacociae against S.cerealella; T. cordubensis against S.cerealella and P. interpunctella and T. euproctidis against P. interpunctella. All tested wasps had a propensity to superparasitize the host eggs. T. cordubensis, T. euproctidis and T. borarachae showed promise for further investigation into selecting new biological control agents against some stored product lepidopterous pests.

Spontaneous pseudo-topological silicon quantization for redesigned Si-based Li-ion batteries

Nano-structured silicon anodes are attractive alternatives to graphite in lithium-ion batteries; however, despite recent progress in nano-engineered composites, its use remains limited. One of the issues, particularly in silicon-dominated anodes, is the poor Coulombic efficiency of lithium–silicon processes. Previous studies have shown that repeating the amorphous–crystalline hysteretic lithium–silicon phase transformations can abruptly improve irreversibility and eventually minimize cumulative irreversible lithium consumption in exchange of certain parasitic capacity sacrifice. Here, we reveal mechanism behind the phenomenon that the single phase transformation spontaneously and pseudo-topologically transforms nano-structured silicon into quantum-scale frameworks without gravimetric loss. The way it forms is clearly distinct from ever explored formation mechanism of porous nano-structures such as (electro)chemical etching, Kirkendall voiding, and percolation theory. Further, we implanted the structural transformation feature into lithium-ion full cells, largely redesigning the conventional one, by modulating cathode/anode capacity loading balance and prelithiation dose in the anode to embed the unique feature in the cells. We show that the cell preferentially triggers the efficient irreversibility-depletion phenomenon upon cycling and consequently outperforms conventional silicon-based cells.

Host-preference and parasitic capacity of five Trichogramma species (Hym.: Trichogrammatidae) against some stored product moth pests: Poster

Host-preference and parasitic capacity of five Trichogramma species (Hym.: Trichogrammatidae) against some stored product moth pests: Poster

Parasitism of Lepidopteran Defoliators of Urban Plants byPalmistichus elaeisis(Hymenoptera: Eulophidae)

Heraclides anchisiades capys (Lepidoptera: Papilionidae), Citioica anthonilis (Lepidoptera: Saturniidae), and Methona themisto (Lepidoptera: Nymphalidae) are tree and shrub pests commonly found in urban areas. The parasitism capacity of Palmistichus elaeisis (Hymenoptera: Eulophidae) was evaluated on pupae of these lepidopteran pests as well as on 2 commonly used alternative hosts, Anticarsia gemmatalis (Lepidoptera: Noctuidae) and Tenebrio molitor (Coleoptera: Tenebrionidae). The number of parasitoids produced per mg of host pupal biomass was significantly greater on H. anchisiades capys and T. molitor compared with the other 3 lepidopteran species. The mean number of parasitoids emerging per host pupa was also significantly more on H. anchisiades capys compared with C. anthonilis, M. themisto, A. gemmatalis, or T. molitor. All host species tested in this study show the potential to be used in mass rearing P. elaeisis in the laboratory. However, the lower parasitism and emergence of P. elaeisis on H. anchisiades capys pupae suggests that this lepidopteran pest may not be a suitable host for this parasitoid in the field.

Parasitism capacity and searching efficiency of Diaeretiella rapae parasitizing Brevicoryne brassicae on susceptible and resistant canola cultivars

Abstract Different cultivars of aplant species can affect the foraging and efficiency of natural enemies, both directly through physical and biochemical properties or indirectly through the herbivore's diet. In this study, the parasitism capacity and functional response of Diaeretiella rapae McIntosh were determined on the cabbage aphid, Brevicoryne brassicae (L.) reared on susceptible (Opera) and resistant (Okapi) canola cultivars under laboratory conditions at 25 ± 1 °C, 60 ± 5% RH and a16:8 h L:D photoperiod. The parasitoid exhibited Type II and Type III functional responses on the resistant and susceptible cultivars, respectively. The estimated value of searching efficiency (a) was 0.1637 ± 0.1095 h−1 on the resistant cultivar whereas its value was dependent on host density on the susceptible cultivar. The handling times (Th) on the susceptible and resistant canola cultivars were 0.108 ± 0.040 and 0.320 ± 0.048 h, respectively. The net parasitism rate (C0) of the parasitoid wasp varied from 128.09 hosts per parasitoid lifetime on the susceptible to 71.01hosts on the resistant canola cultivar. The transformation rate from host population to parasitoid offspring (Qp) was equal to 1 on both cultivars (C0 = R0). The finite parasitism rate (ω) on the susceptible cultivar (0.819 hosts per parasitoid per day) was significantly higher than that on the resistant one (0.578 hosts per parasitoid per day). In conclusion, canola cultivars affected the performance of D. rapae in controlled small-scale laboratory experiments and compared with the susceptible cultivar, the resistant one had anadverseeffect on the efficiency of the parasitoid.

Biological Characteristics and Parasitism Capacity of Telenomus podisi (Hymenoptera: Platygastridae) on Eggs of Euschistus heros (Hemiptera: Pentatomidae)

We evaluated the effects of adult mating and temperature on the biological potential and parasitism of Telenomus podisi (Ashmead) (Hymenoptera: Platygastridae) on Euschistus heros (Fabricius) (Hemiptera: Pentatomidae). Females were isolated and the characteristics of the F1 generation were compared with those of females previously copulated. The parasitism capacity of T. podisi on E. heros eggs at 20, 25, 30, 35, and 40 °C was evaluated. The longevity of parental females (days), egg-adult period (days) of the F1 generation, parasitism of parental females (%), and parasitoid emergence (%) were not influenced by the lack or not of the copulation. The offspring of non-copulated females were males, and arrhenotokous parthenogenesis occurred. The temperatures most favorable to the parasitoid were 25 and 30 °C. Even previously copulated females generated mostly males after a few days of oviposition. Therefore, the biological characteristics and reproduction of T. podisi were impacted by adult mating prior to parasitism and by different temperatures. Although parasitism of T. podisi was not affected by mating parasitoid permanence in the field, it may be affected when unmated females are released.

Sublethal effects of insecticides used in soybean on the parasitoid Trichogramma pretiosum.

To control crop pests, parasitoid wasps of the genus Trichogramma are one alternative to the use of insecticides. Since a wide variety of agrochemicals may be applied to the same crops, it is essential to assess the selectivity of insecticides used for pest control on Trichogramma pretiosum. Information on which insecticides are less harmful to T. pretiosum can improve biological control using this insect, an important tactic in IPM programs for field crops. This study aimed to determine the effects of insecticides on the pupal stage and on the parasitism capacity of T. pretiosum. Lambda-cyhalothrin + thiamethoxam were slightly harmful and chlorpyriphos was moderately harmful to the pupal stage, while acephate, chlorfenapyr and flubendiamide, although considered innocuous, affected the succeeding generations of wasps, with low emergence of F1. Chlorfenapyr, chlorpyriphos and lambda-cyhalothrin + thiamethoxam reduced the parasitism, and acephate had a deleterious effect on the generation that contacted the insecticide residue. For an effective IPM program, it is important to apply selective insecticides. Further studies are needed to determine the selectivity of these insecticides under field conditions.

The impact of parasites during range expansion of an invasive gecko.

Host-parasite dynamics can play a fundamental role in both the establishment success of invasive species and their impact on native wildlife. The net impact of parasites depends on their capacity to switch effectively between native and invasive hosts. Here we explore host-switching, spatial patterns and simple fitness measures in a slow-expanding invasion: the invasion of Asian house geckos (Hemidactylus frenatus) from urban areas into bushland in Northeast Australia. In bushland close to urban edges, H. frenatus co-occurs with, and at many sites now greatly out-numbers, native geckos. We measured prevalence and intensity of Geckobia mites (introduced with H. frenatus), and Waddycephalus (a native pentastome). We recorded a new invasive mite species, and several new host associations for native mites and geckos, but we found no evidence of mite transmission between native and invasive geckos. In contrast, native Waddycephalus nymphs were commonly present in H. frenatus, demonstrating this parasite's capacity to utilize H. frenatus as a novel host. Prevalence of mites on H. frenatus decreased with distance from the urban edge, suggesting parasite release towards the invasion front; however, we found no evidence that mites affect H. frenatus body condition or lifespan. Waddycephalus was present at low prevalence in bushland sites and, although its presence did not affect host body condition, our data suggest that it may reduce host survival. The high relative density of H. frenatus at our sites, and their capacity to harbour Waddycephalus, suggests that there may be impacts on native geckos and snakes through parasite spillback.

Assessing drug efficacy against Plasmodium falciparum liver stages in vivo.

Malaria eradication necessitates new tools to fight the evolving and complex Plasmodium pathogens. These tools include prophylactic drugs that eliminate Plasmodium liver stages and consequently prevent clinical disease, decrease transmission, and reduce the propensity for resistance development. Currently, the identification of these drugs relies on in vitro P. falciparum liver stage assays or in vivo causal prophylaxis assays using rodent malaria parasites; there is no method to directly test in vivo liver stage activity of candidate antimalarials against the human malaria-causing parasite P. falciparum. Here, we use a liver-chimeric humanized mouse (FRG huHep) to demonstrate in vivo P. falciparum liver stage development and describe the efficacy of clinically used and candidate antimalarials with prophylactic activity. We show that daily administration of atovaquone-proguanil (ATQ-PG; ATQ, 30 mg/kg, and PG, 10 mg/kg) protects 5 of 5 mice from liver stage infection, consistent with the use in humans as a causal prophylactic drug. Single-dose primaquine (60 mg/kg) has similar activity to that observed in humans, demonstrating the activity of this drug (and its active metabolites) in FRG huHep mice. We also show that DSM265, a selective Plasmodial dihydroorotate dehydrogenase inhibitor with causal prophylactic activity in humans, reduces liver stage burden in FRG huHep mice. Finally, we measured liver stage-to-blood stage transition of the parasite, the ultimate readout of prophylactic activity and measurement of infective capacity of parasites in the liver, to show that ATQ-PG reduces blood stage patency to below the limit of quantitation by quantitative PCR (qPCR). The FRG huHep model, thus, provides a platform for preclinical evaluation of drug candidates for liver stage causal prophylactic activity, pharmacokinetic/pharmacodynamics studies, and biological studies to investigate the mechanism of action of liver stage active antimalarials.

Oxidative Stress-Mediated Overexpression of Uracil DNA Glycosylase in Leishmania donovani Confers Tolerance against Antileishmanial Drugs.

Leishmania donovani is an intracellular protozoan parasite that causes endemic tropical disease visceral leishmaniasis (VL). Present drugs used against this fatal disease are facing resistance and toxicity issues. Survival of leishmania inside the host cells depends on the parasite's capacity to cope up with highly oxidative environment. Base excision repair (BER) pathway in L. donovani remains unexplored. We studied uracil DNA glycosylase (UNG), the key enzyme involved in BER pathway, and found that the glycosylase activity of recombinant LdUNG (Leishmania donovani UNG) expressed in E. coli is in sync with the activity of the parasite lysate under different reaction conditions. Overexpression of UNG in the parasite enhances its tolerance towards various agents which produce reactive oxygen species (ROS) and shows a higher infectivity in macrophages. Surprisingly, exposure of parasite to amphotericin B and sodium antimony gluconate upregulates the expression of UNG. Further, we found that the drug resistant parasites isolated from VL patients show higher expression of UNG. Mechanisms of action of some currently used drugs include accumulation of ROS. Our findings strongly suggest that targeting LdUNG would be an attractive therapeutic strategy as well as potential measure to tackle the problem of drug resistance in the treatment of leishmaniasis.