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Matthews, J. B.

Publications and source records attributed to Matthews, J. B..

3 recordsLinked to original sources

Cytochrome c oxidase I deep amplicon sequencing for metabarcoding of equine strongyle communities: unexpectedly high Strongylus spp. burden in treated horses

Equines are parasitized by complex communities of Strongylidae (Nematoda) comprising multi-species infections. Currently, the Cyathostominae are most prevalent, while the Strongylus species are only rarely detected. Since eggs and, in most cases, infective larvae cannot be differentiated to species level, with the exception of Strongylus spp., species-specific knowledge of the pathology, epidemiology and ecology of these parasitic nematodes is limited. Reference sequence data for several cyathostomin species are limited or missing. Deep amplicon sequencing of internal transcribed spacer 2 (ITS-2) regions of nematodes has been used in equines previously, although barcoding studies demonstrate a better species resolution for the cytochrome c oxidase subunit I (COI) region. The present study introduces a nemabiome method based on the sequencing of COI fragments. This method was applied to compare third stage larvae, representing strongyle communities, derived from regularly treated (RT) and never treated (NT) equine populations from Brazil, France (only RT), Germany, Ukraine, the UK, and the USA. Samples were predominantly from horses, but some were obtained from Przewalskis horses (Ukraine), donkeys (Germany, Ukraine) and kulans (Ukraine). Most sequence reads (87.7%) were identified to the species level, but unclassified reads occurred more frequently in donkeys and kulans than horses. No obvious difference in species diversity and richness was observed between RT and NT equines. However, there were significant differences in species composition between the RT and NT groups. While Strongylus spp. were significantly more abundant in the NT groups, Cylicocyclus nassatus, Cylicostephanus longibursatus, and Cyathostomum catinatum were more abundant in the RT group, suggesting that strongyle communities in domestic equines may have been shaped by anthelmintic treatments in the last decades. The decreased classification success for reads from non-caballine equines suggests that there are more strongyle species specific for this rarely-investigated group and that additional efforts are needed to improve the sequence database, particularly for these hosts. Author summaryThis study shows that long-term deworming treatments have influenced strongyle nematode communities in equines. Our findings showed that regular deworming does not always reduce species richness and diversity. Noteworthy, we observed that the more pathogenic species such as Strongylus vulgaris and Strongylus edentatus were still present but in low abundance in equines. Due to their low abundance, less sensitive diagnostic methods, such as morphological examination of larval cultures might not detect these species, which would lead to an underestimated threat in equine herds. We applied an effective metabarcoding approach based on a reliable gene marker region to accurately detect these and other strongyle species in equines. The detection of various species was more effective for horse samples than for those from donkeys and kulans. An expansion of the current database that includes more specimens from more rare species obtained from different equine species can improve identification and understanding of these complex multi-species communities in the future. In summary, the study underscores the importance of continuing monitoring equine herds based on sensitive methods such as metabarcoding to evaluate the current nematode communities and to adapt and develop treatment strategies for managing strongyle infections in equines.

microbiology↗

The right time and place: time- and age-dependent vaccine-enhanced mucosal immunity to parasite infection

Individuals vary broadly in their response to vaccination and subsequent exposure to infection, causing persistence of both infection and transmission. The prevalence of poor vaccine responders hampers the development of vaccines, especially against parasitic helminths. Yet despite having substantial economic and societal impact, the immune mechanisms that underlie such variability, especially at the site of parasite infection, remain poorly understood. Previous trials using a prototype vaccine for the control of the gastric parasitic Teladorsagia circumcincta, one of the highest impact parasites affecting sheep, revealed substantial variation in protection between individuals, which we hypothesised may in part be driven by age at vaccination. Here, to characterise how immunity at the mucosal site of infection developed in vaccinated lambs, we inserted gastric cannulae into the abomasa (true stomachs) of three-month- and six-month-old lambs before vaccination, and performed a longitudinal analysis of their local immune response during subsequent challenge infection. We found that the vaccine caused systemic changes in the baseline immune profile within the abomasum before any parasite exposure had occurred and reduced parasite burden and egg output once lambs were infected, regardless of age. However, age affected how vaccinated lambs responded to subsequent infection across multiple immune pathways, with only a minority of protective immune pathways being independent of age. This resulted in younger lambs being more susceptible to infection regardless of vaccine status. The identification of age-dependent (mostly adaptive) and age-independent (mostly innate) protective immune pathways should help refine the formulation of vaccines against these and potentially other helminth parasites of ruminants, and could indicate specificities of anti-helminth immunity more generally.

immunology↗

An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes

Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified known anthelmintics, including tolfenpyrad, auranofin, and mebendazole and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.

pharmacology and toxicology↗