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Krücken, J.

Publications and source records attributed to Krücken, J..

6 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↗

Ghosts of symbionts past: The hidden history of the dynamic association between filarial nematodes and their Wolbachia endosymbionts

Many, but not all, parasitic filarial nematodes (Onchocercidae) carry intracellular, maternally-transmitted Wolbachia symbionts, and these alphaproteobacteria are targets for anti-filarial chemotherapeutic interventions for human disease. The symbionts of Onchocercidae derive from four of the major supergroups (C, D, F and J) defined within the genus Wolbachia. Using twenty-two whole genome sequences of filarial nematodes and genome sequences of their Wolbachia partners, we have explored the evolutionary history of the nematode-Wolbachia symbiosis. We screened the nuclear genome sequences of all the nematodes for nuclear Wolbachia transfers (NUWTs), fragments of the Wolbachia genome that have been integrated into the nuclear genome. Six species have no current Wolbachia infection. Setaria labiatopapillosa had no validated NUWTs and we interpret this to mean that this species was never infected with Wolbachia. In the other five species (Acanthocheilonema viteae, Cercopithifilaria (Ce.) johnstoni, Elaeophora elaphi, Loa (Lo.) loa and Onchocerca flexuosa) we found NUWTs, implying they have previously had and have now lost Wolbachia infections. For each NUWT locus, we identified the supergroup membership of the Wolbachia from which it originated, and found that the five Wolbachia-free species carried NUWTs derived from multiple supergroups, including a high shared rate of sequences derived from supergroup C. In Dirofilaria repens we identified a sample that carried two Wolbachia symbionts, one from supergroup C and one from supergroup F. In Dirofilaria immitis where live infection with a supergroup C Wolbachia is found, we identified NUWTs derived from an F Wolbachia, confirming that the F association predated the divergence of these Dirofilaria species. The supergroup D lineage of Wolbachia, as present in the human parasites Wuchereria bancrofti and Brugia malayi, derives from a replacement event. Madathamugadia (Md.) hiepei shows signs of multiple recent repeated endosymbiont replacement. From these data we infer that the history of Wolbachia in onchocercid nematodes includes not only cospeciation (as present in the Onchocerca-Dirofilaria group in association with supergroup C Wolbachia) and loss (in the five Wolbachia-free species), but also frequent symbiont replacement and dual infection. This dynamic pattern is challenging to models that assume host-symbiont mutualism.

genomics↗

Investigating the consequences of the mating system for drug resistance evolution in C. elegans

The rise of anthelmintic-resistant strains in livestock threatens both animal and human health. Understanding the factors influencing anthelmintic resistance is crucial to mitigate the threat posed by these parasites. Due to difficulties in studying parasitic worms in the laboratory, the non-parasitic nematode Caenorhabditis elegans is used as a model organism to investigate anthelmintic resistance evolution. However, the suitability of this free-living nematode as a model for parasitic worms is debatable due to its rare androdioecious reproductive system, raising questions about the generalizability of findings from evolutionary experiments in C. elegans to other species. In this study, we developed a polygenic, population genetic model combined with pharmacodynamic approaches to investigate the effects of reproductive strategy and other aspects, such as dominance, mutational effects, the number of loci, and population size, on determining the dynamics and outcome of evolutionary processes. We found that androdioecious populations showed both rapid initial adaptation typical for hermaphrodites and tolerance to high drug concentrations observed in dioecious populations. They also exhibited the highest diversity and shortest time for the fixation of the beneficial allele. These results suggest that androdioecious populations can harness the advantages of both selfing and outcrossing, optimizing their reproductive strategy in response to drug selection.

evolutionary biology↗

First evaluation and detection of ivermectin resistance in gastrointestinal nematodes of sheep and goats in South Darfur, Sudan

In Sudan, resistance to benzimidazoles has been reported recently in cattle and goats from South Darfur. Herein, ivermectin efficacy against gastrointestinal nematodes (GINs) was evaluated in sheep and goats in three study areas in South Darfur. The faecal egg count reduction test (FECRT) was used to evaluate the efficacy of ivermectin in sheep and goats naturally infected with GINs in the region of Bulbul (goats: n=106), Kass (goats: n=40) and Nyala (Domaia (sheep: n=47, goats: n=77) and the University farm (goats: n=52)), using different treatment plans, and the efficacy was evaluated 12 days after treatment. Ivermectin efficacy was also evaluated in goats experimentally infected using local Haemonchus contortus isolates from Kass and Nyala. Nematodes surviving ivermectin treatment in goats in Bulbul and Nyala were harvested and larvae used to infect worm-free male sheep (n=6, [≤]6 months old). Infected sheep were dosed subcutaneously with ivermectin every eight days with increasing doses from 0.2 mg/kg to 1.6 mg/kg bodyweight (bw). Reduced ivermectin efficacy was identified in sheep and goats in the four study locations. Using a paired statistic, the efficacy of a therapeutic dose in sheep was 75.6% (90% upper credible limit (UCrL): 77.5%), while twice the recommended dose led to a reduction of 92.6% (90% UCrL: 93.3%). In goats, the FECRs of a therapeutic dose were 72.9 - 95.3% (90% UCrL range: 73.6 - 95.7%) in Bulbul, Nyala Domaia, Nyala University farm and Kass. Twice the dose recommended for goats in Bulbul revealed a 90% UCrL of 87.6%. All post-treatment faecal cultures contained only Haemonchus spp. larvae. The experimental infection trials in sheep and goats supported our findings from field trials and calculated upper 90% CrL of below 98.9%. For the first time highly ivermectin resistant H. contortus populations have been identified in sheep and goats in Sudan, and resistance was experimentally confirmed.

zoology↗

Evaluation of the nemabiome approach for the study of equine strongylid communities

Basic knowledge on the biology and epidemiology of equine strongylid species remains insufficient although it would contribute to the design of better parasite control strategies. Nemabiome is a convenient tool to quantify and to identify species in bulk samples that could overcome the hurdle that cyathostomin morphological identification represents. To date, this approach has relied on the internal transcribed spacer 2 (ITS-2) of the ribosomal RNA cistron and its predictive performance and associated biases both remain unaddressed. This study aimed to bridge this knowledge gap using cyathostomin mock communities and comparing performances of the ITS-2 and a cytochrome c oxidase subunit I (COI) barcode newly developed in this study. The effects of bioinformatic parameters were investigated to determine the best analytical pipelines. Subsequently, barcode predictive abilities were compared across various mock community compositions. The replicability of the approach and the amplification biases of each barcode were estimated. Results were also compared between various types of biological samples, i.e. eggs, infective larvae or adults. Overall, the proposed COI barcode was suboptimal relative to the ITS-2 rDNA region, because of PCR amplification biases, a reduced sensitivity and higher divergence from the expected community composition. Metabarcoding yielded consistent community composition across the three sample types, although infective larvae may remain the most tractable in the field. Additional strategies to improve the COI barcode performances are discussed. These results underscore the critical need of mock communities for metabarcoding purposes.

ecology↗

Pharyngeal pumping and tissue-specific transgenic P-glycoprotein expression influence macrocyclic lactone susceptibility in Caenorhabditis elegans

Macrocyclic lactone (ML) resistance has emerged in many parasitic nematodes including the pathogenic horse roundworm Parascaris univalens. The underlying mechanism of ML resistance and the drug penetration routes into the nematodes remain to be elucidated. Drug efflux by P-glycoproteins is considered a potential resistance mechanism but conclusive functional evidence is lacking. To this end, we used a motility assay modified to stimulate pharyngeal pumping (PP) by bacteria or serotonin and tissue-specific expression of Pun- PGP-9 in the free-living model nematode Caenorhabditis elegans. Here, stimulation of PP was identified as an important factor for C. elegans ML susceptibility, increasing the EC50 values of ivermectin by up to 11.1-fold and of moxidectin by 1.2-fold. In this context, intestinal Pun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation, increasing the EC50 values by approximately 3- to 4-fold (ivermectin) or by < 1.3-fold (moxidectin). Conversely, epidermal Pun-PGP-9 expression protected against moxidectin regardless of PP with EC50 fold changes below 1.5 but against ivermectin with a considerable 2.9-fold EC50 increase only when the drug is not actively ingested. Our results highlight the role of active drug ingestion by nematodes for susceptibility and provide conclusive functional evidence for a contribution of P-glycoproteins to ML resistance. Author SummaryParasitic nematode infections pose a serious threat to animal health, in particular in light of the widespread anthelmintic resistance in different nematode species. In equines, the roundworm Parascaris univalens is a major pathogen of foals, exhibiting widespread resistance against macrocyclic lactones (MLs). This represents a particular challenge to animal health, but the underlying mechanisms and drug penetration routes remain mostly unknown. P-glycoprotein ABC-transporters have been linked to ML resistance in several parasitic nematodes. Here we demonstrate by tissue-specific overexpression of Pun-PGP-9 in the free-living model nematode Caenorhabditis elegans their ability to reduce the susceptibility to two commonly used MLs, ivermectin and moxidectin. At the same time, active drug ingestion by pharyngeal pumping (PP) strongly enhanced ivermectin and moderately effects moxidectin susceptibility. In more detail, the effect of intestinal or epidermal Pun-PGP-9 was dependent on active drug ingestion. These observations indicate differences in the drug penetration routes between ML derivatives and allow novel insight into the functional role of P-glycoproteins.

pharmacology and toxicology↗