Veterinary Biosciences - Research Publications
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ItemThermal proteome profiling reveals Haemonchus orphan protein HCO_011565 as a target of the nematocidal small molecule UMW-868(FRONTIERS MEDIA SA, 2022-10-14)Parasitic roundworms (nematodes) cause destructive diseases, and immense suffering in humans and other animals around the world. The control of these parasites relies heavily on anthelmintic therapy, but treatment failures and resistance to these drugs are widespread. As efforts to develop vaccines against parasitic nematodes have been largely unsuccessful, there is an increased focus on discovering new anthelmintic entities to combat drug resistant worms. Here, we employed thermal proteome profiling (TPP) to explore hit pharmacology and to support optimisation of a hit compound (UMW-868), identified in a high-throughput whole-worm, phenotypic screen. Using advanced structural prediction and docking tools, we inferred an entirely novel, parasite-specific target (HCO_011565) of this anthelmintic small molecule in the highly pathogenic, blood-feeding barber's pole worm, and in other socioeconomically important parasitic nematodes. The "hit-to-target" workflow constructed here provides a unique prospect of accelerating the simultaneous discovery of novel anthelmintics and associated parasite-specific targets.
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ItemPhylogenetic Relationships of the Strongyloid Nematodes of Australasian Marsupials Based on Mitochondrial Protein Sequences(MDPI, 2022-11)Australasian marsupials harbour a diverse group of gastrointestinal strongyloid nematodes. These nematodes are currently grouped into two subfamilies, namely the Cloacininae and Phascolostrongylinae. Based on morphological criteria, the Cloacininae and Phascolostrongylinae were defined as monophyletic and placed in the family Cloacinidae, but this has not been supported by molecular data and they are currently placed in the Chabertiidae. Although molecular data (internal transcribed spacers of the nuclear ribosomal RNA genes or mitochondrial protein-coding genes) have been used to verify morphological classifications within the Cloacininae and Phascolostrongylinae, the phylogenetic relationships between the subfamilies have not been rigorously tested. This study determined the phylogenetic relationships of the subfamilies Cloacininae and Phascolostrongylinae using amino acid sequences conceptually translated from the twelve concatenated mitochondrial protein-coding genes. The findings demonstrated that the Cloacininae and Phascolostrongylinae formed a well-supported monophyletic assemblage, consistent with their morphological classification as an independent family, Cloacinidae. Unexpectedly, however, the subfamily Phascolostrongylinae was split into two groups comprising the genera from macropodid hosts (kangaroos and wallabies) and those from vombatid hosts (wombats). Genera of the Cloacininae and Phascolostrongylinae occurring in macropodid hosts were more closely related compared to genera of the Phascolostrongylinae occurring in wombats that formed a sister relationship with the remaining genera from macropods. These findings provide molecular evidence supporting the monophyly of the family Cloacinidae and an alternative hypothesis for the origin of marsupial strongyloid nematodes in vombatid hosts that requires further exploration using molecular approaches and additional samples.
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ItemPhysiological, Biochemical, and Yield Responses of Linseed (Linum usitatissimum L.) in α-Tocopherol-Mediated Alleviation of Salinity Stress.(Frontiers Media SA, 2022)Exogenous application of antioxidants can be helpful for plants to resist salinity, which can be a potentially simple, economical, and culturally feasible approach, compared with introgression and genetic engineering. Foliar spraying of alpha-tocopherol (α-tocopherol) is an approach to improve plant growth under salinity stress. Alpha-tocopherol acts as an antioxidant preventing salinity-induced cellular oxidation. This study was designed to investigate the negative effects of salinity (0 and 120mM NaCl) on linseed (Linum usitatissimum L.) and their alleviation by foliar spraying of α-tocopherol (0, 100, and 200mg L-1). Seeds of varieties "Chandni and Roshni" were grown in sand-filled plastic pots, laid in a completely randomized design in a factorial arrangement, and each treatment was replicated three times. Salinity significantly affected linseed morphology and yield by reducing shoot and root dry weights, photosynthetic pigment (Chl. a, Chl. b, total Chl., and carotenoids) contents, mineral ion (Ca2+, K+) uptake, and 100-seed weight. Concomitantly, salinity increased Na+, proline, soluble protein, peroxidase, catalase, and superoxide dismutase activities in both varieties. Conversely, the growth and yield of linseed varieties were significantly restored by foliar spraying of α-tocopherol under saline conditions, improving shoot and root dry matter accumulation, photosynthetic pigment, mineral ion, proline, soluble protein contents, peroxidase, catalase, superoxide dismutase activities, and 100-seed weight. Moreover, foliar spray of α-tocopherol alleviated the effects of salinity stress by reducing the Na+ concentration and enhancing K+ and Ca2+ uptake. The Chandni variety performed better than the Roshni, for all growth and physiological parameters studied. Foliar spray of α-tocopherol (200mg L-1) alleviated salinity effects by improving the antioxidant potential of linseed varieties, which ultimately restored growth and yield. Therefore, the use of α-tocopherol may enhance the productivity of linseed and other crops under saline soils.
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ItemNo Preview AvailableThe occurrence of multidrug-resistant Mycobacterium tuberculosis from patients of pulmonary tuberculosis.(Journal of Infection in Developing Countries, 2022-04-30)INTRODUCTION: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is one of the leading causes of death in the world. The resource constraints make it difficult to diagnose and monitor the cases of MDR-TB. GeneXpert is a recognized tool used to diagnose the patients of pulmonary tuberculosis in clinical settings across the globe. METHODOLOGY: The present one-year cross-sectional study was conducted to estimate the occurrence of MDR-TB in patients with pulmonary TB. A total of 1000 patients suspected of pulmonary tuberculosis were included in this study. A random convenient sampling technique was done to collect the sputum samples (twice) from the patients. Samples were processed for the detection of Mycobacterium tuberculosis using conventional detection methods like the Ziehl Nelson staining method and fluorescent microscopy. Additionally, Cepheid GeneXpert was used for molecular detection of MDR-TB in smear-positive samples of pulmonary tuberculosis by amplifying the rifampicin resistance determining region (RRDR; rpoB gene). All the tests were performed in the biosafety level III lab of District Headquarters Hospital Nankana Sahib. RESULTS: It was observed that 103 (10.3%) individuals were diagnosed as positive for tuberculosis among 1000 patients. Among these 103 TB positive cases, there were 11 (10.7%) patients diagnosed with rifampicin resistance gene (RR-Gene) of Mycobacterium tuberculosis. CONCLUSIONS: Overall findings of the study showed that MDR-TB is prevalent in pulmonary TB patients and GeneXpert is the most sensitive technique for early diagnosis of the disease, which may be very helpful in the treatment and control of this public health menace in low and middle-income countries.
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ItemCharacterisation of drug-resistant Mycobacterium tuberculosis mutations and transmission in Pakistan.(Springer Science and Business Media LLC, 2022-05-11)Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = 328; 61.3%) and (pre-)XDR (n = 113; 21.1%). By inferring close genomic relatedness between isolates (< 10-SNPs difference), there was evidence of M. tuberculosis transmission, with 55 clusters formed consisting of a total of 169 isolates. Three clusters consist of M. tuberculosis that are similar to isolates found outside of Pakistan. A genome-wide association analysis comparing 'transmitted' and 'non-transmitted' isolate groups, revealed the nusG gene as most significantly associated with a potential transmissible phenotype (P = 5.8 × 10-10). Overall, our study provides important insights into M. tuberculosis genetic diversity and transmission in Pakistan, including providing information on circulating drug resistance mutations for monitoring activities and clinical decision making.
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ItemPhylogenetic Relationships within the Nematode Subfamily Phascolostrongylinae (Nematoda: Strongyloidea) from Australian Macropodid and Vombatid Marsupials( 2020-09-30)Abstract Background: The strongyloid nematode subfamily Phascolostrongylinae are parasites of the large intestine and stomach of Australian macropods (Macropodidae) and wombats (Vombatidae). Based on morphological classifications, the Phascolostrongylinae is comprised of seven genera belonging to three tribes (Phascolostrongylinea, Macropostrongyloidinea, and Hypodontinea). The phylogenetic relationships among the genera of the Phascolostrongylinae were tested using the first and second internal transcribed spacer (ITS+) sequences of the ribosomal DNA. Results: Monophyly was encountered in the tribe Phascolostrongylinea comprising two genera, Phascolostrongylus and Oesophagostomoides, found exclusively in the large intestine of wombats. The tribe Hypodontinea, represented by the genera Hypodontus and Macropicola from the ileum and large intestine of macropods was also found to be monophyletic, but with low support. The tribe Macropostrongyloidinea comprising the genera Macropostrongyloides and Paramacropostrongylus was paraphyletic with the species occurring in the stomach grouping separately to those found in the large intestines of their hosts. Finally, Macropostrongyloides dissimilis from the stomach of the swamp wallaby and Paramacropostrongylus toraliformis from the large intestine of the eastern grey kangaroo were distinct from their respective congeners. Conclusion: The current study provided strong support for the generic composition of the tribe Phascolostrongylinea and low support for the tribe Hypodontinea. However, the relationships within the tribe Macropostrongyloidinea are more complex and its monophyly was not supported by the current ITS+ dataset. The unexpected finding of M. dissimilis and P. toraliformis being distantly related to their respective congeners suggests a requirement for future taxonomic revision which may warrant separation of these species at the generic level.
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ItemAdvances in the discovery and development of anthelmintics by harnessing natural product scaffolds(ELSEVIER ACADEMIC PRESS INC, 2021)Widespread resistance to currently-used anthelmintics represents a major obstacle to controlling parasitic nematodes of livestock animals. Given the reliance on anthelmintics in many control regimens, there is a need for the continued discovery and development of new nematocides. Enabling such a focus are: (i) the major chemical diversity of natural products; (ii) the availability of curated, drug-like extract-, fraction- and/or compound-libraries from natural sources; (iii) the utility and practicality of well-established whole-worm bioassays for Haemonchus contortus-an important parasitic nematodes of livestock-to screen natural product libraries; and (iv) the availability of advanced chromatographic (HPLC), spectroscopic (NMR) and spectrometric (MS) techniques for bioassay-guided fractionation and structural elucidation. This context provides a sound basis for the identification and characterisation of anthelmintic candidates from natural sources. This chapter provides a background on the importance and impact of helminth infections/diseases, parasite control and aspects of drug discovery, and reviews recent work focused on (i) screening well-defined compound libraries to establish the methods needed for large-scale screening of natural extract libraries; (ii) discovering plant and marine extracts with nematocidal or nematostatic activity, and purifying bioactive compounds and assessing their potential for further development; and (iii) synthesising analogues of selected purified natural compounds for the identification of possible 'lead' candidates. The chapter describes some lessons learned from this work and proposes future areas of focus for drug discovery. Collectively, the findings from this recent work show potential for selected natural product scaffolds as candidates for future development. Developing such candidates via future chemical optimisation, efficacy and safety evaluations, broad spectrum activity assessments, and target identification represents an exciting prospect and, if successful, could pave the way to subsequent pre-clinical and clinical evaluations.
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ItemTicks and tick-borne diseases of bovines in a smallholder livestock context: The Pakistani example(ELSEVIER ACADEMIC PRESS INC, 2021)Ticks and tick-borne diseases (TTBDs) substantially affect the health and production of ruminants, particularly in resource-poor, small-scale farming systems worldwide. However, to date, there has been no critical appraisal of the current state of knowledge of TTBDs in such farming systems. In this article, we systematically reviewed the situation in Pakistan-as an example of a country that is highly reliant on agriculture to sustain its economy, particularly smallholder livestock farms, which are continually faced with challenges associated with TTBDs. The main aims of this review were to gain improved insights into the current status of TTBDs in small-scale farming systems, and to identify knowledge gaps, through the systematic evaluation of published literature on this topic from Pakistan, and to recommend future research directions. We searched publicly available literature from three databases (i.e. Web of Science, Google Scholar, and PubMed) on bovine TTBDs in Pakistan. Of 11,224 published studies identified, 185 were eligible for inclusion; these studies were published between August 1947 and June 2021. A critical analysis of these 185 studies revealed that the diagnosis of ticks and tick-borne pathogens (TBPs) in Pakistan has been based largely on the use of traditional methods (i.e. 'morpho-taxonomy'). At least 54 species of tick have been recorded, most of which belong to the genera Haemaphysalis, Hyalomma and Rhipicephalus. The prevalence of ticks was higher, particularly in young, exotic and crossbred female cattle, during the summer season. Major TBPs include species of Anaplasma, Babesia and Theileria, with prevalences being higher in cattle than buffaloes. Additionally, pathogens of zoonotic potential, including species of Anaplasma, Borrelia, the Crimean-Congo haemorrhagic fever virus, Coxiella, Ehrlichia and Rickettsia, have been recorded in both tick and bovine populations. Information on risk factors, spatial-temporal distribution, genetic diversity, and control of ticks and TBPs is limited, the vector potential of ticks and the distribution patterns of ticks and TBPs in relation to climate remains largely unexplored. Future research should focus on addressing these knowledge gaps and the key challenges of poverty, food security and disease outbreaks in a small-scale livestock farming context in order to provide sustainable, environment-friendly control measures for TTBDs.
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ItemRedescription of Rugopharynx australis (Monnig, 1926) and the description of R. moennigi n. sp. (Nematoda: Strongyloidea) from kangaroos (Marsupialia: Macropodidae) in Australia(SPRINGER, 2021-12)Rugopharynx australis (Mönnig, 1926) (Nematoda: Strongyloidea) is redescribed based on specimens from the type host, Osphranter rufus (Desmarest), together with matching DNA sequence data. Additional hosts were Macropus giganteus Shaw and Osphranter robustus (Gould) with single occurrences in M. fuliginosus (Desmarest), Notamacropus dorsalis (Gray), Lagorchestes conspicillatus Gould and Petrogale xanthopus Gray. Rugopharynx moennigi n. sp., formerly included within R. australis, is distinguished by shorter but overlapping spicule lengths and in the morphology of the gubernaculum as well as by molecular data. Rugopharynx moennigi n. sp. appears to be primarily parasitic in M. fuliginosus throughout its geographical range, but also infects M. giganteus, O. robustus and O. rufus in areas of host sympatry.
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ItemImpact of climate change on tick-borne diseases of livestock in Pakistan – looking ahead(CABI, 2022)This expert opinion summarizes the current status of ticks and tick-borne diseases of ruminants in Pakistan. It also assesses the evidence of climate change and its likely impact on the abundance and distribution of ticks and the prevalence and intensity of tick-borne diseases affecting livestock in the country.