Addition of activated carbon into a cattle diet to mitigate GHG emissions and improve production
- Al-Azzawi, Mohammed, Bowtell, Les, Hancock, Kerry, Preston, Sarah
- Authors: Al-Azzawi, Mohammed , Bowtell, Les , Hancock, Kerry , Preston, Sarah
- Date: 2021
- Type: Text , Journal article
- Relation: Sustainability (Switzerland) Vol. 13, no. 15 (2021), p.
- Full Text:
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- Description: Globally, the most problematic greenhouse gas (GHG) emissions of ruminant livestock is methane (CH4), with a global warming potential 25 times that of carbon dioxide. This work considers the emissions and production effects of powdered activated carbon (PAC) at 0.5% by dry matter (DM) on methanogenic rumen flora as the major source of dairy cattle enteric methane emissions. In total, 180 dairy cattle located in Brymaroo, Queensland (QLD), Australia, were studied in a three-cycle repeated measures ANOVA format with a 4 week primary interval. Emissions eructated during milking and in faecal deposits were measured, and in addition, 16S rRNA gene sequencing was performed to determine the collective populations of prokaryotic bacteria and archaea as well methanogenic communities for each treatment. Moreover, 0.5% PAC addition reduced CH4 emissions by 30-40% and CO2 emissions by 10%, while improving daily milk production by 3.43%, milk protein by 2.63% and milk fat by 6.32%, on average for the herd (p < 0.001 in all cases). rRNA gene sequencing showed populations of methanogenic flora decreased by 30% on average with a corresponding increase in the nonmethanogenic species. We strongly advocate further on-farm trials with the dietary addition of PAC in ruminant diets to mitigate emissions while maintaining or improving productivity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Authors: Al-Azzawi, Mohammed , Bowtell, Les , Hancock, Kerry , Preston, Sarah
- Date: 2021
- Type: Text , Journal article
- Relation: Sustainability (Switzerland) Vol. 13, no. 15 (2021), p.
- Full Text:
- Reviewed:
- Description: Globally, the most problematic greenhouse gas (GHG) emissions of ruminant livestock is methane (CH4), with a global warming potential 25 times that of carbon dioxide. This work considers the emissions and production effects of powdered activated carbon (PAC) at 0.5% by dry matter (DM) on methanogenic rumen flora as the major source of dairy cattle enteric methane emissions. In total, 180 dairy cattle located in Brymaroo, Queensland (QLD), Australia, were studied in a three-cycle repeated measures ANOVA format with a 4 week primary interval. Emissions eructated during milking and in faecal deposits were measured, and in addition, 16S rRNA gene sequencing was performed to determine the collective populations of prokaryotic bacteria and archaea as well methanogenic communities for each treatment. Moreover, 0.5% PAC addition reduced CH4 emissions by 30-40% and CO2 emissions by 10%, while improving daily milk production by 3.43%, milk protein by 2.63% and milk fat by 6.32%, on average for the herd (p < 0.001 in all cases). rRNA gene sequencing showed populations of methanogenic flora decreased by 30% on average with a corresponding increase in the nonmethanogenic species. We strongly advocate further on-farm trials with the dietary addition of PAC in ruminant diets to mitigate emissions while maintaining or improving productivity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Arylpyrrole and fipronil analogues that inhibit the motility and/or development of Haemonchus contortus in vitro
- Herath, Dilrukshi, Song, Hongjian, Preston, Sarah, Jabbar, Abdul, Wang, Tao, McGee, Sean, Hofmann, Andreas, Garcia-Bustos, Jose, Chang, Bill, Koehler, Anson, Liu, Yuxiu, Ma, Qiaoqiao, Zhang, Penqxiang, Zhao, Qiqi, Wang, Qingmin, Gasser, Robin
- Authors: Herath, Dilrukshi , Song, Hongjian , Preston, Sarah , Jabbar, Abdul , Wang, Tao , McGee, Sean , Hofmann, Andreas , Garcia-Bustos, Jose , Chang, Bill , Koehler, Anson , Liu, Yuxiu , Ma, Qiaoqiao , Zhang, Penqxiang , Zhao, Qiqi , Wang, Qingmin , Gasser, Robin
- Date: 2018
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 8, no. 3 (2018), p. 379-385
- Full Text:
- Reviewed:
- Description: Due to widespread drug resistance in parasitic nematodes, there is a need to develop new anthelmintics. Given the cost and time involved in developing a new drug, the repurposing of known chemicals can be a promising, alternative approach. In this context, we tested a library (n = 600) of natural product-inspired pesticide analogues against exsheathed third stage-larvae (xL3s) of Haemonchus contortus (barber's pole worm) using a whole-organism, phenotypic screening technique that measures the inhibition of motility and development in treated larvae. In the primary screen, we identified 32 active analogues derived from chemical scaffolds of arylpyrrole or fipronil. The seven most promising compounds, selected based on their anthelmintic activity and/or limited cytotoxicity, are arylpyrroles that reduced the motility of fourth-stage larvae (L4s) with significant potency (IC 50 values ranged from 0.04 ± 0.01
- Authors: Herath, Dilrukshi , Song, Hongjian , Preston, Sarah , Jabbar, Abdul , Wang, Tao , McGee, Sean , Hofmann, Andreas , Garcia-Bustos, Jose , Chang, Bill , Koehler, Anson , Liu, Yuxiu , Ma, Qiaoqiao , Zhang, Penqxiang , Zhao, Qiqi , Wang, Qingmin , Gasser, Robin
- Date: 2018
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 8, no. 3 (2018), p. 379-385
- Full Text:
- Reviewed:
- Description: Due to widespread drug resistance in parasitic nematodes, there is a need to develop new anthelmintics. Given the cost and time involved in developing a new drug, the repurposing of known chemicals can be a promising, alternative approach. In this context, we tested a library (n = 600) of natural product-inspired pesticide analogues against exsheathed third stage-larvae (xL3s) of Haemonchus contortus (barber's pole worm) using a whole-organism, phenotypic screening technique that measures the inhibition of motility and development in treated larvae. In the primary screen, we identified 32 active analogues derived from chemical scaffolds of arylpyrrole or fipronil. The seven most promising compounds, selected based on their anthelmintic activity and/or limited cytotoxicity, are arylpyrroles that reduced the motility of fourth-stage larvae (L4s) with significant potency (IC 50 values ranged from 0.04 ± 0.01
- Herath, Dilrukshi, Preston, Sarah, Hofmann, Andreas, Davis, Rohan, Koehler, Anson, Chang, Bill, Jabbar, Abdul, Gasser, Robin
- Authors: Herath, Dilrukshi , Preston, Sarah , Hofmann, Andreas , Davis, Rohan , Koehler, Anson , Chang, Bill , Jabbar, Abdul , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 244, no. (2017), p. 172-175
- Full Text: false
- Reviewed:
- Description: The control of parasitic roundworms (nematodes) is heavily reliant on the use of a limited number of anthelmintic drugs. However, drug resistance is now very widespread and no vaccines are available, such that the discovery of new chemical entities is crucial. Within this context, we screened a library of pure natural products (n = 400) against exsheathed third-stage (xL3) larvae of the parasitic nematode Haemonchus contortus using a whole-organism screening method. We identified two plant-derived rotenoids, deguelin and rotenone, with inhibitory activity on xL3 motility. Rotenone was not investigated further, because of its toxicity to some vertebrates. The dose response and cytotoxicity studies showed potent and selective inhibitory activity of deguelin on motility of xL3 larvae of H. contortus. Detailed future work needs to be conducted to explore the mode of action of this compound on H. contortus and related nematodes, and to assess its potential as an anthelmintic candidate. © 2017 Elsevier B.V.
Selected alpha-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro
- Herath, Dilrukshi, Preston, Sarah, Jabbar, Abdul, Garcia-Bustos, Jose, Addison, Russell, Hayes, Sasha, Rali, Topul, Wang, Tao, Koehler, Anson, Chang, Bill, Hofmann, Andreas, Davis, Rohan, Gasser, Robin
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Addison, Russell , Hayes, Sasha , Rali, Topul , Wang, Tao , Koehler, Anson , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: International Journal for Parasitology-Drugs and Drug Resistance Vol. 9, no. (2019), p. 72-79
- Full Text:
- Reviewed:
- Description: Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four alpha-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC50 values of 31.7 +/- 0.23 mu M and 23.7 +/- 2.05 mu M, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC50 of 200-300 mu M) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC50 of 6.25-12.50 mu M). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of alpha-pyrones should be pursued to assess their potential as anthelmintics.
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Addison, Russell , Hayes, Sasha , Rali, Topul , Wang, Tao , Koehler, Anson , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: International Journal for Parasitology-Drugs and Drug Resistance Vol. 9, no. (2019), p. 72-79
- Full Text:
- Reviewed:
- Description: Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four alpha-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC50 values of 31.7 +/- 0.23 mu M and 23.7 +/- 2.05 mu M, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC50 of 200-300 mu M) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC50 of 6.25-12.50 mu M). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of alpha-pyrones should be pursued to assess their potential as anthelmintics.
Identification of fromiamycalin and halaminol A from Australian marine sponge extracts with anthelmintic activity against haemonchus contortus
- Herath, Dilrukshi, Preston, Sarah, Jabbar, Abdul, Garcia-Bustos, Jose, Taki, Aya, Addison, Russell, Hayes, Sasha, Beattie, Karren, McGee, Sean, Martin, Sheree, Ekin, Merrick, Hooper, John, Chang, Bill, Hofmann, Andreas, Davis, Rohan, Gasser, Robin
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Taki, Aya , Addison, Russell , Hayes, Sasha , Beattie, Karren , McGee, Sean , Martin, Sheree , Ekin, Merrick , Hooper, John , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Marine Drugs Vol. 17, no. 11 (Nov 2019), p. 14
- Full Text:
- Reviewed:
- Description: There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus - a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 +/- 0.74 mu M) and L4 motility (IC50 = 39.4 +/- 4.83 mu M), although it had a relatively low potency at inhibiting of xL3 motility (IC50 >= 100 mu M). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Taki, Aya , Addison, Russell , Hayes, Sasha , Beattie, Karren , McGee, Sean , Martin, Sheree , Ekin, Merrick , Hooper, John , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Marine Drugs Vol. 17, no. 11 (Nov 2019), p. 14
- Full Text:
- Reviewed:
- Description: There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus - a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 +/- 0.74 mu M) and L4 motility (IC50 = 39.4 +/- 4.83 mu M), although it had a relatively low potency at inhibiting of xL3 motility (IC50 >= 100 mu M). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.
DRfit : A Java tool for the analysis of discrete data from multi-well plate assays
- Hofmann, Andreas, Preston, Sarah, Cross, Megan, Herath, Dilrukshi, Simon, Anne, Gasser, Robin
- Authors: Hofmann, Andreas , Preston, Sarah , Cross, Megan , Herath, Dilrukshi , Simon, Anne , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 20, no. (2019), p. 1-6
- Full Text:
- Reviewed:
- Description: Background: Analyses of replicates in sets of discrete data, typically acquired in multi-well plate formats, is a recurring task in many contemporary areas in the Life Sciences. The availability of accessible cross-platform data analysis tools for such fundamental tasks in varied projects and environments is an important prerequisite to ensuring a reliable and timely turnaround as well as to provide practical analytical tools for student training. Results: We have developed an easy-to-use, interactive software tool for the analysis of multiple data sets comprising replicates of discrete bivariate data points. For each dataset, the software identifies the replicate data points from a defined matrix layout and calculates their means and standard errors. The averaged values are then automatically fitted using either a linear or a logistic dose response function. Conclusions: DRfit is a practical and convenient tool for the analysis of one or multiple sets of discrete data points acquired as replicates from multi-well plate assays. The design of the graphical user interface and the built-in analysis features make it a flexible and useful tool for a wide range of different assays.
- Authors: Hofmann, Andreas , Preston, Sarah , Cross, Megan , Herath, Dilrukshi , Simon, Anne , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: BMC Bioinformatics Vol. 20, no. (2019), p. 1-6
- Full Text:
- Reviewed:
- Description: Background: Analyses of replicates in sets of discrete data, typically acquired in multi-well plate formats, is a recurring task in many contemporary areas in the Life Sciences. The availability of accessible cross-platform data analysis tools for such fundamental tasks in varied projects and environments is an important prerequisite to ensuring a reliable and timely turnaround as well as to provide practical analytical tools for student training. Results: We have developed an easy-to-use, interactive software tool for the analysis of multiple data sets comprising replicates of discrete bivariate data points. For each dataset, the software identifies the replicate data points from a defined matrix layout and calculates their means and standard errors. The averaged values are then automatically fitted using either a linear or a logistic dose response function. Conclusions: DRfit is a practical and convenient tool for the analysis of one or multiple sets of discrete data points acquired as replicates from multi-well plate assays. The design of the graphical user interface and the built-in analysis features make it a flexible and useful tool for a wide range of different assays.
Quantifying the sources of variation in eosinophilia among Scottish blackface lambs with mixed, predominantly Teladorsagia circumcincta nematode infection
- Jenvey, Caitlin, Almasi, Fazel, Halliwell, Emma, Piedrafita, David, Preston, Sarah
- Authors: Jenvey, Caitlin , Almasi, Fazel , Halliwell, Emma , Piedrafita, David , Preston, Sarah
- Date: 2021
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 300, no. (2021), p.
- Full Text:
- Reviewed:
- Description: Eosinophils play a key role in defence against gastrointestinal nematodes. There is considerable variation among animals in the intensity of eosinophilia following nematode infection. However, the statistical distribution of eosinophils among animals has still to be determined. A better description of the variation among animals could provide biological insight and determine the most appropriate way to analyse the effect of eosinophils. We estimated blood eosinophil numbers in a flock of Scottish Blackface sheep that were naturally exposed to mixed, predominantly Teladorsagia circumcincta infection. Three of the four eosinophil counts were better described by a gamma distribution than by a lognormal distribution. The scale and shape parameters of the gamma distribution varied over time. Eosinophil counts differed among animals kept on separate fields before weaning and between singletons and twins but were not significantly different between years and genders. Eosinophil counts also differed among offspring from different sires and dams. The parameters of the gamma distribution were used to enable a power analysis. Large numbers of animals were required to reliably detect even large differences between two groups. These results indicate that methods appropriate for gamma distributions, such as generalized linear mixed models, will provide more reliable inferences than traditional methods of analysis and experimental design. © 2021 The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “David Piedrafita and Sarah Preston” is provided in this record**
- Authors: Jenvey, Caitlin , Almasi, Fazel , Halliwell, Emma , Piedrafita, David , Preston, Sarah
- Date: 2021
- Type: Text , Journal article
- Relation: Veterinary Parasitology Vol. 300, no. (2021), p.
- Full Text:
- Reviewed:
- Description: Eosinophils play a key role in defence against gastrointestinal nematodes. There is considerable variation among animals in the intensity of eosinophilia following nematode infection. However, the statistical distribution of eosinophils among animals has still to be determined. A better description of the variation among animals could provide biological insight and determine the most appropriate way to analyse the effect of eosinophils. We estimated blood eosinophil numbers in a flock of Scottish Blackface sheep that were naturally exposed to mixed, predominantly Teladorsagia circumcincta infection. Three of the four eosinophil counts were better described by a gamma distribution than by a lognormal distribution. The scale and shape parameters of the gamma distribution varied over time. Eosinophil counts differed among animals kept on separate fields before weaning and between singletons and twins but were not significantly different between years and genders. Eosinophil counts also differed among offspring from different sires and dams. The parameters of the gamma distribution were used to enable a power analysis. Large numbers of animals were required to reliably detect even large differences between two groups. These results indicate that methods appropriate for gamma distributions, such as generalized linear mixed models, will provide more reliable inferences than traditional methods of analysis and experimental design. © 2021 The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “David Piedrafita and Sarah Preston” is provided in this record**
Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus
- Jiao, Yaqing, Preston, Sarah, Song, Hongjian, Jabbar, Abdul, Liu, Yuxiu, Baell, Jonathan, Hofmann, Andreas, Hutchinson, Dana, Wang, Tao, Koehler, Anson, Fisher, Gillian, Andrews, Katherine, Laleu, Benoit, Palmer, Michael, Burrows, Jeremy, Wells, Timothy, Wang, Qingmin, Gasser, Robin
- Authors: Jiao, Yaqing , Preston, Sarah , Song, Hongjian , Jabbar, Abdul , Liu, Yuxiu , Baell, Jonathan , Hofmann, Andreas , Hutchinson, Dana , Wang, Tao , Koehler, Anson , Fisher, Gillian , Andrews, Katherine , Laleu, Benoit , Palmer, Michael , Burrows, Jeremy , Wells, Timothy , Wang, Qingmin , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 10, no. 1 (2017), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber’s pole worm), one of the most pathogenic parasites of ruminants. Methods: In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus. Results: Amongst the 55 compounds, we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xL3 motility as well as L4 motility and development, with IC50 values ranging between ~3.4 and 55.6 μM. We studied the effect of these two ‘hit’ compounds on mitochondrial function by measuring oxygen consumption. This assessment showed that xL3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xL3s, which was consistent with specific inhibition of complex I of the respiratory electron transport chain in arthropods. Conclusions: The present findings provide a sound basis for future work, aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in H. contortus. © 2017 The Author(s).
- Authors: Jiao, Yaqing , Preston, Sarah , Song, Hongjian , Jabbar, Abdul , Liu, Yuxiu , Baell, Jonathan , Hofmann, Andreas , Hutchinson, Dana , Wang, Tao , Koehler, Anson , Fisher, Gillian , Andrews, Katherine , Laleu, Benoit , Palmer, Michael , Burrows, Jeremy , Wells, Timothy , Wang, Qingmin , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 10, no. 1 (2017), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber’s pole worm), one of the most pathogenic parasites of ruminants. Methods: In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus. Results: Amongst the 55 compounds, we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xL3 motility as well as L4 motility and development, with IC50 values ranging between ~3.4 and 55.6 μM. We studied the effect of these two ‘hit’ compounds on mitochondrial function by measuring oxygen consumption. This assessment showed that xL3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xL3s, which was consistent with specific inhibition of complex I of the respiratory electron transport chain in arthropods. Conclusions: The present findings provide a sound basis for future work, aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in H. contortus. © 2017 The Author(s).
Metabolic profiling and in vitro assessment of anthelmintic fractions of Picria fel-terrae Lour
- Kumarasingha, Rasika, Karpe, Avinash, Preston, Sarah, Yeo, Tiong-Chia, Lim, Diana, Tu, Chu-Lee, Luu, Jennii, Simpson, Kaylene, Shaw, Jillian, Gasser, Robin, Beale, David, Morrison, Paul, Palombo, Enzo, Boag, Peter
- Authors: Kumarasingha, Rasika , Karpe, Avinash , Preston, Sarah , Yeo, Tiong-Chia , Lim, Diana , Tu, Chu-Lee , Luu, Jennii , Simpson, Kaylene , Shaw, Jillian , Gasser, Robin , Beale, David , Morrison, Paul , Palombo, Enzo , Boag, Peter
- Date: 2016
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 6, no. 3 (2016), p. 171-178
- Full Text:
- Reviewed:
- Description: Anthelmintic resistance is widespread in gastrointestinal nematode populations, such that there is a consistent need to search for new anthelmintics. However, the cost of screening for new compounds is high and has a very low success rate. Using the knowledge of traditional healers from Borneo Rainforests (Sarawak, Malaysia), we have previously shown that some traditional medicinal plants are a rich source of potential new anthelmintic drug candidates. In this study, Picria fel-terrae Lour. plant extract, which has previously shown promising anthelmintic activities, was fractionated via the use of a solid phase extraction cartridge and each isolated fraction was then tested on free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. We found that a single fraction was enriched for nematocidal activity, killing ≥90% of C. elegans adults and inhibiting the motility of exsheathed L3 of H. contortus, while having minimal cytotoxic activity in mammalian cell culture. Metabolic profiling and chemometric analysis of the effective fraction indicated medium chained fatty acids and phenolic acids were highly represented. Image 1 •Chemical fractionation of Picria fel-terrae Lour. plant extract.•Anthelmintic activity against Caenorhabditis elegans and Haemonchus contortus.•Metabolic profiling and chemometric analysis of active fraction.•Active fraction has minimal mammalian cytotoxicity.
- Authors: Kumarasingha, Rasika , Karpe, Avinash , Preston, Sarah , Yeo, Tiong-Chia , Lim, Diana , Tu, Chu-Lee , Luu, Jennii , Simpson, Kaylene , Shaw, Jillian , Gasser, Robin , Beale, David , Morrison, Paul , Palombo, Enzo , Boag, Peter
- Date: 2016
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 6, no. 3 (2016), p. 171-178
- Full Text:
- Reviewed:
- Description: Anthelmintic resistance is widespread in gastrointestinal nematode populations, such that there is a consistent need to search for new anthelmintics. However, the cost of screening for new compounds is high and has a very low success rate. Using the knowledge of traditional healers from Borneo Rainforests (Sarawak, Malaysia), we have previously shown that some traditional medicinal plants are a rich source of potential new anthelmintic drug candidates. In this study, Picria fel-terrae Lour. plant extract, which has previously shown promising anthelmintic activities, was fractionated via the use of a solid phase extraction cartridge and each isolated fraction was then tested on free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. We found that a single fraction was enriched for nematocidal activity, killing ≥90% of C. elegans adults and inhibiting the motility of exsheathed L3 of H. contortus, while having minimal cytotoxic activity in mammalian cell culture. Metabolic profiling and chemometric analysis of the effective fraction indicated medium chained fatty acids and phenolic acids were highly represented. Image 1 •Chemical fractionation of Picria fel-terrae Lour. plant extract.•Anthelmintic activity against Caenorhabditis elegans and Haemonchus contortus.•Metabolic profiling and chemometric analysis of active fraction.•Active fraction has minimal mammalian cytotoxicity.
Anthelmintic activity of selected ethno-medicinal plant extracts on parasitic stages of Haemonchus contortus
- Kumarasingha, Rasika, Preston, Sarah, Yeo, Tiong-Chia, Lim, Diana, Tu, Chu-Lee, Palombo, Enzo, Shaw, Jillian, Gasser, Robin, Boag, Peter
- Authors: Kumarasingha, Rasika , Preston, Sarah , Yeo, Tiong-Chia , Lim, Diana , Tu, Chu-Lee , Palombo, Enzo , Shaw, Jillian , Gasser, Robin , Boag, Peter
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 9, no. 1 (2016), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future. Methods: Recently, we developed a screening assay to test natural, plant extracts with known inhibitory effects against the free-living worm Caenorhabditis elegans. Using this assay, we assessed here the effects of the extracts on motility and development of parasitic larval stages of Haemonchus contortus, one of the most important nematodes of small ruminants worldwide. Results: The study showed that two of five extracts from Picria fel-terrae Lour. have a significant inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and development of H. contortus larvae. Although the two extracts originated from the same plant, they displayed different levels of inhibition on motility and development, which might relate to the presence of various active constituents in these extracts, or the same constituents at different concentrations in distinct parts of the plant. Conclusions: These results suggest that extracts from P. fel-terrae Lour. have promising anthelmintic activity and that more broadly, plant extracts are a potential rich source of anthelmintics to combat helminthic diseases. © 2016 Kumarasingha et al.
- Authors: Kumarasingha, Rasika , Preston, Sarah , Yeo, Tiong-Chia , Lim, Diana , Tu, Chu-Lee , Palombo, Enzo , Shaw, Jillian , Gasser, Robin , Boag, Peter
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 9, no. 1 (2016), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future. Methods: Recently, we developed a screening assay to test natural, plant extracts with known inhibitory effects against the free-living worm Caenorhabditis elegans. Using this assay, we assessed here the effects of the extracts on motility and development of parasitic larval stages of Haemonchus contortus, one of the most important nematodes of small ruminants worldwide. Results: The study showed that two of five extracts from Picria fel-terrae Lour. have a significant inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and development of H. contortus larvae. Although the two extracts originated from the same plant, they displayed different levels of inhibition on motility and development, which might relate to the presence of various active constituents in these extracts, or the same constituents at different concentrations in distinct parts of the plant. Conclusions: These results suggest that extracts from P. fel-terrae Lour. have promising anthelmintic activity and that more broadly, plant extracts are a potential rich source of anthelmintics to combat helminthic diseases. © 2016 Kumarasingha et al.
- Le, Thuy, Kundu, Abhijit, Ghoshal, Atanu, Nguyen, Nghi, Preston, Sarah, Jiao, Yaqing, Ruan, Banfeng, Xue, Lian, Huang, Fei, Keiser, Jennifer, Hofmann, Andreas, Chang, Bill, Garcia-Bustos, Jose, Wells, Timothy, Palmer, Michael, Jabbar, Abdul, Gasser, Robin, Baell, Jonathan
- Authors: Le, Thuy , Kundu, Abhijit , Ghoshal, Atanu , Nguyen, Nghi , Preston, Sarah , Jiao, Yaqing , Ruan, Banfeng , Xue, Lian , Huang, Fei , Keiser, Jennifer , Hofmann, Andreas , Chang, Bill , Garcia-Bustos, Jose , Wells, Timothy , Palmer, Michael , Jabbar, Abdul , Gasser, Robin , Baell, Jonathan
- Date: 2019
- Type: Text , Journal article
- Relation: Journal of Medicinal Chemistry Vol. 62, no. 2 (2019), p. 1036-1053
- Full Text: false
- Reviewed:
- Description: Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 mu M while displaying good selectivity, with an IC50 of 37.9 mu M for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.
Novel 1-Methyl-1H-pyrazole-5-carboxamide derivatives with potent anthelmintic activity
- Le, Thuy, Kundu, Abhijit, Ghoshal, Atanu, Nguyen, Nghi, Preston, Sarah, Jiao, Yaqing, Ruan, Banfeng, Xue, Lian, Huang, Fei, Keiser, Jennifer, Hofmann, Andreas, Chang, Bill, Garcia-Bustos, Jose, Wells, Timothy, Palmer, Michael, Jabbar, Abdul, Gasser, Robin, Baell, Jonathan
- Authors: Le, Thuy , Kundu, Abhijit , Ghoshal, Atanu , Nguyen, Nghi , Preston, Sarah , Jiao, Yaqing , Ruan, Banfeng , Xue, Lian , Huang, Fei , Keiser, Jennifer , Hofmann, Andreas , Chang, Bill , Garcia-Bustos, Jose , Wells, Timothy , Palmer, Michael , Jabbar, Abdul , Gasser, Robin , Baell, Jonathan
- Date: 2019
- Type: Text , Journal article
- Relation: Journal of Medicinal Chemistry Vol. 62, no. 7 (2019), p. 3367-3380
- Full Text: false
- Reviewed:
- Description: A phenotypic screen of two different libraries of small molecules against the motility and development of the parasitic nematode Haemonchus contortus led to the identification of two 1-methyl-1H-pyrazole-5-carboxamide derivatives. Medicinal chemistry optimization targeted modifications of the left-hand side, middle section, and right-hand side of the hybrid structure of these two hits to elucidate the structure-activity relationship (SAR). Initial SAR around these hits allowed for the iterative and directed assembly of a focused set of 30 analogues of their hybrid structure. Compounds 10, 17, 20, and 22 were identified as the most potent compounds, inhibiting the development of the fourth larval (L4) stage of H. contortus at sub-nanomolar potencies while displaying strong selectivity toward the parasite when tested in vitro against the human MCF10A cell line. In addition, compounds 9 and 27 showed promising activity against a panel of other parasitic nematodes, including hookworms and whipworms.
- Le, Thuy, Kunda, Abhijit, Ghoshal, Atanu, Preston, Sarah, Jiao, Yaqing, Ruan, Banfeng, Xue, Lian, Huang, Fei, Keiser, Jennifer, Hofmann, Andreas, Chang, Bill, Garcia-Bustos, Jose, Jabbar, Abdul, Wells, Timothy, Palmer, Michael, Gasser, Robin, Baell, Jonathan
- Authors: Le, Thuy , Kunda, Abhijit , Ghoshal, Atanu , Preston, Sarah , Jiao, Yaqing , Ruan, Banfeng , Xue, Lian , Huang, Fei , Keiser, Jennifer , Hofmann, Andreas , Chang, Bill , Garcia-Bustos, Jose , Jabbar, Abdul , Wells, Timothy , Palmer, Michael , Gasser, Robin , Baell, Jonathan
- Date: 2018
- Type: Text , Journal article
- Relation: Journal of Medicinal Chemistry Vol. 61, no. 23 (2018), p. 10875-10894
- Full Text: false
- Reviewed:
- Description: A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC
Phenotypic screening of the 'Kurz-box' of chemicals identifies two compounds (BLK127 and HBK4) with anthelmintic activity in vitro against parasitic larval stages of Haemonchus contortus
- Nguyen, Linh, Kurz, Thomas, Preston, Sarah, Brueckmann, Hjoerdis, Lungerich, Beate, Herath, Dilrukshi, Koehler, Anson, Wang, Tao, Skalova, Lenka, Jabbar, Abdul, Gasser, Robin
- Authors: Nguyen, Linh , Kurz, Thomas , Preston, Sarah , Brueckmann, Hjoerdis , Lungerich, Beate , Herath, Dilrukshi , Koehler, Anson , Wang, Tao , Skalova, Lenka , Jabbar, Abdul , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Parasites & Vectors Vol. 12, no. (2019), p. 1-9
- Full Text:
- Reviewed:
- Description: BackgroundDue to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants.MethodsIn the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay.ResultsOf the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a curved' phenotype in both xL3s and L4s.ConclusionsThe findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.
- Authors: Nguyen, Linh , Kurz, Thomas , Preston, Sarah , Brueckmann, Hjoerdis , Lungerich, Beate , Herath, Dilrukshi , Koehler, Anson , Wang, Tao , Skalova, Lenka , Jabbar, Abdul , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Parasites & Vectors Vol. 12, no. (2019), p. 1-9
- Full Text:
- Reviewed:
- Description: BackgroundDue to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants.MethodsIn the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay.ResultsOf the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a curved' phenotype in both xL3s and L4s.ConclusionsThe findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.
The heritability of Nematodirus battus fecal egg counts
- Nikbin, Saeid, Almasi, Fazel, Alenizi, Dalal, Jenvey, Caitlin, Sloan, Sarah, Preston, Sarah, Piedrafita, David, Jonsson, Nicholas, Stear, Michael
- Authors: Nikbin, Saeid , Almasi, Fazel , Alenizi, Dalal , Jenvey, Caitlin , Sloan, Sarah , Preston, Sarah , Piedrafita, David , Jonsson, Nicholas , Stear, Michael
- Date: 2022
- Type: Text , Journal article
- Relation: Parasitology Vol. 149, no. 4 (2022), p. 555-561
- Full Text:
- Reviewed:
- Description: Although Nematodirus battus is a serious threat to the health and survival of young lambs, there are few options to control this parasite. Bayesian Monte Carlo Markov Chain modelling with a zero-inflated Poisson distribution was used to estimate the heritability of egg counts in both June and July for each of five consecutive cohorts of 200 Scottish Blackface lambs. In one of the 10 analyses, the results failed the diagnostic tests. In seven of the analyses, there was no convincing evidence that the variation in egg counts was heritable. In the 2 years of high infection, the heritability was approximately 0.4 in June but the estimates lacked precision and the 95% highest posterior density credible intervals ranged from just above zero to 0.7. Selective breeding for resistance to N. battus will be difficult because genetically resistant or susceptible lambs cannot be consistently identified by phenotypic markers. © The Author(s) 2022.
- Authors: Nikbin, Saeid , Almasi, Fazel , Alenizi, Dalal , Jenvey, Caitlin , Sloan, Sarah , Preston, Sarah , Piedrafita, David , Jonsson, Nicholas , Stear, Michael
- Date: 2022
- Type: Text , Journal article
- Relation: Parasitology Vol. 149, no. 4 (2022), p. 555-561
- Full Text:
- Reviewed:
- Description: Although Nematodirus battus is a serious threat to the health and survival of young lambs, there are few options to control this parasite. Bayesian Monte Carlo Markov Chain modelling with a zero-inflated Poisson distribution was used to estimate the heritability of egg counts in both June and July for each of five consecutive cohorts of 200 Scottish Blackface lambs. In one of the 10 analyses, the results failed the diagnostic tests. In seven of the analyses, there was no convincing evidence that the variation in egg counts was heritable. In the 2 years of high infection, the heritability was approximately 0.4 in June but the estimates lacked precision and the 95% highest posterior density credible intervals ranged from just above zero to 0.7. Selective breeding for resistance to N. battus will be difficult because genetically resistant or susceptible lambs cannot be consistently identified by phenotypic markers. © The Author(s) 2022.
The effect of different adjuvants on immune parameters and protection following vaccination of sheep with a larval-specific antigen of the gastrointestinal nematode, Haemonchus contortus
- Piedrafita, David, Preston, Sarah, Kemp, Joanna, De Veer, Michael, Sherrard, Jayne, Kraska, Troy, Elhay, Martin, Meeusen, Els
- Authors: Piedrafita, David , Preston, Sarah , Kemp, Joanna , De Veer, Michael , Sherrard, Jayne , Kraska, Troy , Elhay, Martin , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE. Vol. 8, no. 10, (Art. no.e78357) (2013), p. 1-8
- Full Text:
- Reviewed:
- Description: It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC) and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection. Funding: Australian Research Council Linkage grant LP0668945 and the ARC-Centre of Excellence in Structural and Functional Microbial Genomics. The funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip
- Authors: Piedrafita, David , Preston, Sarah , Kemp, Joanna , De Veer, Michael , Sherrard, Jayne , Kraska, Troy , Elhay, Martin , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS ONE. Vol. 8, no. 10, (Art. no.e78357) (2013), p. 1-8
- Full Text:
- Reviewed:
- Description: It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC) and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection. Funding: Australian Research Council Linkage grant LP0668945 and the ARC-Centre of Excellence in Structural and Functional Microbial Genomics. The funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip
Current status for gastrointestinal nematode diagnosis in small ruminants: where are we and where are we going?
- Preston, Sarah, Sandeman, Mark, Gonzalez, Jorge, Piedrafita, David
- Authors: Preston, Sarah , Sandeman, Mark , Gonzalez, Jorge , Piedrafita, David
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of immunology research Vol. 2014, no. September (2014), p. Article no. 210350
- Full Text:
- Reviewed:
- Description: Gastrointestinal nematode (GIN) parasites pose a significant economic burden particularly in small ruminant production systems. Anthelmintic resistance is a serious concern to the effective control of GIN parasites and has fuelled the focus to design and promote sustainable control of practices of parasite control. Many facets of sustainable GIN parasite control programs rely on the ability to diagnose infection both qualitatively and quantitatively. Diagnostics are required to determine anthelmintic efficacies, for targeted treatment programs and selection of animals for parasite resistant breeding. This review describes much of the research investigated to date to improve the current diagnostic for the above practices which is based on counting the number of parasite eggs in faeces.
- Authors: Preston, Sarah , Sandeman, Mark , Gonzalez, Jorge , Piedrafita, David
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of immunology research Vol. 2014, no. September (2014), p. Article no. 210350
- Full Text:
- Reviewed:
- Description: Gastrointestinal nematode (GIN) parasites pose a significant economic burden particularly in small ruminant production systems. Anthelmintic resistance is a serious concern to the effective control of GIN parasites and has fuelled the focus to design and promote sustainable control of practices of parasite control. Many facets of sustainable GIN parasite control programs rely on the ability to diagnose infection both qualitatively and quantitatively. Diagnostics are required to determine anthelmintic efficacies, for targeted treatment programs and selection of animals for parasite resistant breeding. This review describes much of the research investigated to date to improve the current diagnostic for the above practices which is based on counting the number of parasite eggs in faeces.
- Preston, Sarah, Beddoe, Travis, Walkden-Brown, Stephen, Meeusen, Els, Piedrafita, David
- Authors: Preston, Sarah , Beddoe, Travis , Walkden-Brown, Stephen , Meeusen, Els , Piedrafita, David
- Date: 2015
- Type: Text , Journal article
- Relation: International Journal for Parasitology Vol. 45, no. 12 (2015), p. 791-796
- Full Text: false
- Reviewed:
- Description: Galectin-11 is released from epithelial cells of the gastrointestinal tract, specifically following infection with gastrointestinal parasites including the highly pathogenic nematode, Haemonchus contortus. The function(s) of galectin-11 are currently unknown but seem to be associated with the development of immunity by the host. The aim of the present study was to examine the interaction of galectin-11 with the different parasitic life cycle stages of H. contortus and determine any effects on parasite development. The results of this study showed that galectin-11 binds to the surface of the L4 and adult stages of the parasite but not to the exsheathed L3 stage. In addition, at a lower concentration, binding to the L4 was specifically localised to the pharynx region. Subsequent in vitro assays demonstrated significant inhibition of larval growth and development in the presence of recombinant galectin-11. These results indicate, to our knowledge for the first time, a functional role for galectin-11 in gastrointestinal nematode infection of ruminants and a mechanism of action of galectin-11, targeting the development and growth of the L4 and possibly the adult parasite stage. © 2015 .
- Preston, Sarah, Luo, Junjie, Zhang, Yuezhou, Jabbar, Abdul, Crawford, Simon, Baell, Jonathan, Hofmann, Andreas, Hu, Min, Zhou, Hai-Bing, Gasser, Robin
- Authors: Preston, Sarah , Luo, Junjie , Zhang, Yuezhou , Jabbar, Abdul , Crawford, Simon , Baell, Jonathan , Hofmann, Andreas , Hu, Min , Zhou, Hai-Bing , Gasser, Robin
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites & Vectors Vol. 9, no. 1 (2016), p. 346
- Full Text: false
- Reviewed:
- Description: Parasitic worms represent a substantial disease burden in animals and humans worldwide. The control of parasitic roundworms (nematodes) relies heavily on the use of anthelmintic drugs. However, widespread drug resistance in nematodes seriously compromises the effectiveness of many anthelmintics around the world. Thus, there is a need to discover new drugs, with unique modes of action, against parasites.
Screening of the ‘Open Scaffolds’ collection from Compounds Australia identifies a new chemical entity with anthelmintic activities against different developmental stages of the barber's pole worm and other parasitic nematodes
- Preston, Sarah, Jiao, Yaqing, Baell, Jonathan, Keiser, Jennifer, Crawford, Simon, Koehler, Anson, Wang, Tao, Simpson, Moana, Kaplan, Ray, Cowley, Karla, Simpson, Kaylene, Hofmann, Andreas, Jabbar, Abdul, Gasser, Robin
- Authors: Preston, Sarah , Jiao, Yaqing , Baell, Jonathan , Keiser, Jennifer , Crawford, Simon , Koehler, Anson , Wang, Tao , Simpson, Moana , Kaplan, Ray , Cowley, Karla , Simpson, Kaylene , Hofmann, Andreas , Jabbar, Abdul , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 7, no. 3 (2017), p. 286-294
- Full Text:
- Reviewed:
- Description: The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the ‘Open Scaffolds’ collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the ‘Open Scaffolds’ collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays. We identified a hit compound, called SN00797439, which was shown to reproducibly reduce xL3 motility by ≥ 70%; this compound induced a characteristic, “coiled” xL3 phenotype (IC50 = 3.46–5.93 μM), inhibited motility of fourth-stage larvae (L4s; IC50 = 0.31–12.5 μM) and caused considerable cuticular damage to L4s in vitro. When tested on other parasitic nematodes in vitro, SN00797439 was shown to inhibit (IC50 = 3–50 μM) adults of Ancylostoma ceylanicum (hookworm) and first-stage larvae of Trichuris muris (whipworm) and eventually kill (>90%) these stages. Furthermore, this compound completely inhibited the motility of female and male adults of Brugia malayi (50–100 μM) as well as microfilariae of both B. malayi and Dirofilaria immitis (heartworm). Overall, these results show that SN00797439 acts against genetically (evolutionarily) distant parasitic nematodes i.e. H. contortus and A. ceylanicum [strongyloids] vs. B. malayi and D. immitis [filarioids] vs. T. muris [enoplid], and, thus, might offer a novel, lead-like scaffold for the development of a relatively broad-spectrum anthelmintic. Our future work will focus on assessing the activity of SN00797439 against other pathogens that cause neglected tropical diseases, optimising analogs with improved biological activities and characterising their targets. © 2017 The Authors
- Authors: Preston, Sarah , Jiao, Yaqing , Baell, Jonathan , Keiser, Jennifer , Crawford, Simon , Koehler, Anson , Wang, Tao , Simpson, Moana , Kaplan, Ray , Cowley, Karla , Simpson, Kaylene , Hofmann, Andreas , Jabbar, Abdul , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 7, no. 3 (2017), p. 286-294
- Full Text:
- Reviewed:
- Description: The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the ‘Open Scaffolds’ collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the ‘Open Scaffolds’ collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays. We identified a hit compound, called SN00797439, which was shown to reproducibly reduce xL3 motility by ≥ 70%; this compound induced a characteristic, “coiled” xL3 phenotype (IC50 = 3.46–5.93 μM), inhibited motility of fourth-stage larvae (L4s; IC50 = 0.31–12.5 μM) and caused considerable cuticular damage to L4s in vitro. When tested on other parasitic nematodes in vitro, SN00797439 was shown to inhibit (IC50 = 3–50 μM) adults of Ancylostoma ceylanicum (hookworm) and first-stage larvae of Trichuris muris (whipworm) and eventually kill (>90%) these stages. Furthermore, this compound completely inhibited the motility of female and male adults of Brugia malayi (50–100 μM) as well as microfilariae of both B. malayi and Dirofilaria immitis (heartworm). Overall, these results show that SN00797439 acts against genetically (evolutionarily) distant parasitic nematodes i.e. H. contortus and A. ceylanicum [strongyloids] vs. B. malayi and D. immitis [filarioids] vs. T. muris [enoplid], and, thus, might offer a novel, lead-like scaffold for the development of a relatively broad-spectrum anthelmintic. Our future work will focus on assessing the activity of SN00797439 against other pathogens that cause neglected tropical diseases, optimising analogs with improved biological activities and characterising their targets. © 2017 The Authors