Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine research

Geldhof, Peter; Clark, Douglas; Molloy, Cathryn; Knox, David P.

doi:10.1016/j.molbiopara.2006.12.006

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…This approach could have merit, given recent success achieved for Teladorsagia circumcincta with a cocktail of recombinant proteins (Nisbet et al, 2013). Table 1 Full length transcripts representing the different Hc-ap genes and the genomic scaffolds to which they map, including the lengths of inferred amino acid sequences and InterProScan matches (including domains and motifs) for individual predicted proteins (this study) as well as for published H11 isoforms Zhou et al, 2010) and Caenorhabditis elegans homologs (Baset et al, 1998;Lyczak et al, 2006;Geldhof et al, 2007;Benner et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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The complement of family M1 aminopeptidases of Haemonchus contortus — Biotechnological implications

Mohandas

Young

Jabbar

et al. 2016

Biotechnology Advances

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Although substantial research has been focused on the 'hidden antigen' H11 of Haemonchus contortus as a vaccine against haemonchosis in small ruminants, little is know about this and related aminopeptidases. In the present article, we reviewed genomic and transcriptomic data sets to define, for the first time, the complement of aminopeptidases (designated Hc-AP-1 to Hc-AP-13) of the family M1 with homologues in Caenorhabditis elegans, characterised by zinc-binding (HEXXH) and exo-peptidase (GAMEN) motifs. The three previously published H11 isoforms (accession nos. X94187, FJ481146 and AJ249941) had most sequence similarity to Hc-AP-2 and Hc-AP-8, whereas unpublished isoforms (accession nos. AJ249942 and AJ311316) were both most similar to Hc-AP-3. The aminopeptidases characterised here had homologues in C. elegans. Hc-AP-1 to Hc-AP-8 were most similar in amino acid sequence (28-41%) to C. elegans T07F10.1; Hc-AP-9 and Hc-AP-10 to C. elegans PAM-1 (isoform b) (53-54% similar); Hc-AP-11 and Hc-AP-12 to C. elegans AC3.5 and Y67D8C.9 (26% and 50% similar, respectively); and Hc-AP-13 to C. elegans C42C1.11 and ZC416.6 (50-58% similar). Comparative analysis suggested that Hc-AP-1 to Hc-AP-8 play roles in digestion, metabolite excretion, neuropeptide processing and/or osmotic regulation, with Hc-AP-4 and Hc-AP-7 having male-specific functional roles. The analysis also indicated that Hc-AP-9 and Hc-AP-10 might be involved in the degradation of cyclin (B3) and required to complete meiosis. Hc-AP-11 represents a leucyl/cystinyl aminopeptidase, predicted to have metallopeptidase and zinc ion binding activity, whereas Hc-AP-12 likely encodes an aminopeptidase Q homologue also with these activities and a possible role in gonad function. Finally, Hc-AP-13 is predicted to encode an aminopeptidase AP-1 homologue of C. elegans with hydrolase activity, suggested to operate, possibly synergistically with a PEPT-1 ortholog, as an oligopeptide transporter in the gut for protein uptake and normal development and/or reproduction of the worm. An appraisal of structure-based amino acid sequence alignments revealed that all conceptually translated Hc-AP proteins, with the exception of Hc-AP-12, adopt a topology similar to those observed for the two subgroups of mammalian M1 aminopeptidases, which possess either three (I, II and IV) or four (I-IV) domains. In contrast, Hc-AP-12 lacks the N-terminal domain (I), but possesses a substantially expanded domain III. Although further work needs to be done to assess amino acid sequence conservation of the different aminopeptidases among individual worms within and among H. contortus populations, we hope that these insights will support future localisation, structural and functional studies of these molecules in H. contortus as well as facilitate future assessments of a recombinant subunit or cocktail vaccine against haemonchosis.

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Section: Discussionmentioning

confidence: 99%

“…Hc-AP-1 to Hc-AP-8, which shared most similarity/homology to T07F10.1 (cf. Geldhof et al, 2007) formed a separate clade to the exclusion of Hc-AP-11, which clustered with AC3.5 isoform b (pp = 1.00). Predicted proteins Hc-AP-9 and Hc-AP-10 clustered with C. elegans PAM-1 isoform b (cf.…”

Section: Comparative Analyses With C Elegans and Functions Predictementioning

confidence: 99%

The complement of family M1 aminopeptidases of Haemonchus contortus — Biotechnological implications

Mohandas

Young

Jabbar

et al. 2016

Biotechnology Advances

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“…However, with the exception of the vaccine against D. viviparus, no vaccines are currently available commercially for the control of helminth infections in ruminants (Knox et al 2001). Few of the experimental vaccines have proceeded to or successfully passed the next phase of development, which is the largescale, cost-effective production of the vaccine (Geldhof et al 2007;Redmond & Knox 2006). Hence, vaccines against parasites are unlikely to become available for the control of worms on farms within the next decade.…”

Section: Vaccinationmentioning

confidence: 99%

A review of the epidemiology and control of gastrointestinal nematode infections in cattle in Zimbabwe

Pfukenyi

Mukaratirwa

2013

Onderstepoort J Vet Res

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In this review, the main gastrointestinal nematodes infecting cattle in Zimbabwe and the epidemiological factors influencing their occurrence are reviewed and discussed. Nineteen gastrointestinal nematode species that belong to seven families have been found to occur in cattle in Zimbabwe. The main genera reported to date are Cooperia, Haemonchus, Trichostrongylus and Oesophagostomum and the dominant species are Cooperia pectinata, Cooperia punctata, Haemonchus placei and Trichostrongylus axei. The mixed infection by several species from the genera is the cause of parasitic gastroenteritis in cattle in Zimbabwe. Production and husbandry practices, season, host age and environment are considered to be the main factors that influence gastrointestinal nematode infection in cattle. The geographical distribution of the gastrointestinal nematodes is also reviewed in relation to the climatic conditions of the country. Various control options are discussed and how they are applicable to the Zimbabwean situation. Based on reports and existing data on the epidemiological features of the gastrointestinal nematode infection in cattle, practical control measures are critically reviewed and recommendations are made for a national control programme.

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“…With the exception of the vaccine against Dictyocaulus viviparus, however, no vaccines are currently available commercially for the control of helminth infections in ruminants. More than 40 years of research have resulted in the identification of several antigens or mixtures of antigens that confer high levels of protection against many species of helminths (Knox et al, 2001), but few of these experimental vaccines have proceeded to or successfully passed the next phase of development, which is the large-scale, cost-effective production of the vaccine (Geldhof et al, 2007;Redmond and Knox, 2006).…”

Section: Hopes and Dreams Behind Vaccine Technologymentioning

confidence: 99%

Challenges of nematode control in ruminants: Focus on Latin America

Molento

Fortes

Pondelek

et al. 2011

Veterinary Parasitology

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Gastrointestinal nematodes (GIN) of ruminants (cattle, sheep and goats) are ubiquitous and can cause severe injuries to infected animals and significant losses in farming revenues. GIN are able to survive severe environmental and host conditions, but mankind has developed a number of ingenious methods for parasite control. The commerce and use of modern anthelmintic drugs with a broad spectrum of activity has been a solid tool for nearly 40 years, however the continuous use of these drugs, has led to the selection of populations of drug-resistant worms worldwide. At present, the ever-growing agricultural systems in Latin America are facing many challenges and cannot rely on the far-reaching objective of parasitic elimination from the host or the environment. The lack of extensive programs for monitoring drug resistance exacerbates the negative consequences of reduced efficacy, which is evident in some areas with the increase in mortality rate even after treatment. Experts agree that new schemes of parasitic control are needed and should be based on the strategy of targeted selective treatment where affected hosts are identified and treated accordingly. In this article, we will focus our discussion on the challenges for the control of GIN in Latin America by 2020 imposed by reduced drug efficacy. We will evaluate phenotypic and molecular markers, methods for single-animal evaluation, and the implementation of schemes for anthelmintic treatment that address parasites in refugia.

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Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine research

Cited by 5 publications

References 14 publications

The complement of family M1 aminopeptidases of Haemonchus contortus — Biotechnological implications

The complement of family M1 aminopeptidases of Haemonchus contortus — Biotechnological implications

A review of the epidemiology and control of gastrointestinal nematode infections in cattle in Zimbabwe

Challenges of nematode control in ruminants: Focus on Latin America

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