Absence of Polymorphisms in Codons 167, 198 and 200 of All Seven β-Tubulin Isotypes of Benzimidazole Susceptible and Resistant Parascaris spp. Specimens from Australia

Özben, Murat; Samson‐Himmelstjerna, Georg von; Streit, Malene K. B. Freiin von; Wilkes, Edwina; Hughes, Kristopher; Krücken, Jürgen

doi:10.3390/pathogens11050490

Cited by 6 publications

(5 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…trichiura isotype 1 to sit within a clade with A. suum isotype E and C. elegans isotype 4 (4). Finally, the relationship between ascarid isotype F and strongyle isotype 3 and between ascarid isotype E and strongyle isotype 4 matches that seen previously with these isotypes forming their own clade (7,9,49). There are several possible causes for the differences seen between our phylogeny and those previously published such as the method used to construct the phylogeny, or the sequences used.…”

Section: Discussionsupporting

confidence: 79%

“…isotype 1 and 2 clusters were found to be at a basal position within the larger A, C, D, B, and G clade, whereas in our phylogeny, we see them form a separate clade (7,9,49). Within this clade, the relationship between the strongyles and C. elegans corresponds to previous work with C. elegans isotypes 1 and 2 being closely related to but isolated from strongyle isotype 1 and C. elegans ben-1 being basal to this clade.…”

Section: Discussioncontrasting

confidence: 66%

“…The phylogenies show that there are noticeable differences between the structuring of the ascarid and strongyle b-tubulins included in this study. There are some noticeable differences seen between the phylogeny presented here and phylogenies presented in recent studies of ascarid b-tubulins (7,9,49). While the general ordering of isotypes in our study is similar to that reported in previous studies, the exact clustering and evolutionary relationship is different.…”

Section: Discussionsupporting

confidence: 50%

“…In our phylogeny, we see a continuous branching off of isotypes A, C, and D, with B and G, and E and F forming separate subsequent clusters. In previous work A, C, and D cluster together with B and G forming a separate cluster, and they together form a larger clade separate from E and F (7,9,49). Again, in previous work, the strongyle The table shows the type of bonds formed (H-hydrogen bond, IH-ionic hydrogen bond, A-arene bond), the amino acid the bond is formed with, and the drug used (ABZSO = albendazole sulfoxide).…”

Section: Discussionmentioning

confidence: 92%

See 3 more Smart Citations

In Silico Docking of Nematode β-Tubulins With Benzimidazoles Points to Gene Expression and Orthologue Variation as Factors in Anthelmintic Resistance

Jones¹,

Vliet²,

LaCourse³

et al. 2022

Front. Trop. Dis

View full text Add to dashboard Cite

The efficacy of benzimidazole anthelmintics can vary depending on the target parasite, with Ascaris nematodes being highly responsive, and whipworms being less responsive. Anthelmintic resistance has become widespread, particularly in strongyle nematodes such as Haemonchus contortus in ruminants, and resistance has recently been detected in hookworms of humans and dogs. Past work has shown that there are multiple β-tubulin isotypes in helminths, yet only a few of these contribute to benzimidazole interactions and resistance. The β-tubulin isotypes of ascarids and soil-transmitted helminths were identified by mining available genome data, and phylogenetic analysis showed that the ascarids share a similar repertoire of seven β-tubulin isotypes. Strongyles also have a consistent pattern of four β-tubulin isotypes. In contrast, the whipworms only have two isotypes, with one of these clustering more basally and distinct from any other group. Key β-tubulin isotypes selected based on previous studies were the focus of in silico molecular docking simulations to look at the interactions with benzimidazoles. These showed that all β-tubulins had similar interactions with benzimidazoles and maintained the key bond with residue E198 in all species, indicating similar mechanisms of action. However, the interaction was stronger and more consistent in the strongyles and whipworms than it was in the ascarids. Alteration of β-tubulin isotypes with the common resistance-associated mutations originally identified in H. contortus resulted in similar interaction modeling for all species. In conclusion, ascarids, strongyles, and whipworms all have their own unique repertoire of β-tubulins, which could explain why benzimidazole resistance and susceptibility varies between these groups of parasites. These data complement recent work that has highlighted the roles of essential residues in benzimidazole drug binding and shows that there is a separation between strongyle parasites that frequently develop resistance and ascarid parasites, which have been much less prone to developing resistance.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussioncontrasting

confidence: 66%

Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 92%

See 2 more Smart Citations

In Silico Docking of Nematode β-Tubulins With Benzimidazoles Points to Gene Expression and Orthologue Variation as Factors in Anthelmintic Resistance

Jones¹,

Vliet²,

LaCourse³

et al. 2022

Front. Trop. Dis

View full text Add to dashboard Cite

show abstract

“…Resistance to the BZDs has been commonly reported in the equine industry worldwide (Matthews, 2014 ) and in wild equids (Kuzmina et al ., 2020 ), showing that resistance against this anthelmintic drug class is not always associated with the intensity of anthelmintic treatments. In horse strongyle infection, resistance to the BZDs has been associated with the polymorphisms of codons 167, 168 and 200 of isotype 1 β -tubulin (Ishii et al ., 2017 ; Özben et al ., 2022 ). In horses, since 2000, AR against BZDs has been evaluated in 58 studies and it was reported in all of them (Nielsen, 2022 ).…”

Section: Ar In Equids: Horses Vs Donkeysmentioning

confidence: 99%

Horse and donkey parasitology: differences and analogies for a correct diagnostic and management of major helminth infections

et al. 2023

View full text Add to dashboard Cite

In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed. Although these 2 species are genetically different, they can be challenged by a similar range of parasites (i.e. small and large strongyles, and Parascaris spp.). Although equids can demonstrate some level of resilience to parasites, they have quite distinct helminth biodiversity, distribution and intensity among different geographical locations and breeds. Heavily infected donkeys may show fewer clinical signs than horses. Although parasite control is primarily provided to horses, we consider that there may be a risk of drug-resistance parasitic infection through passive infection in donkeys when sharing the same pasture areas. Knowing the possible lack of drug efficacy (<90 or 80%), it is advocated the use of selective treatment for both species based on fecal egg counts. Adult horses should receive treatment when the threshold exceeds 200–500 eggs per gram (EPG) of small strongyles. Moreover, considering that there are no precise indications in donkeys, a value >300 EPG may be a safe recommendation. We have highlighted the main points of the discussion including the dynamics of helminth infections between the 2 species.

show abstract

The equine ascarids: resuscitating historic model organisms for modern purposes

Cain

Nielsen

2022

Parasitol Res

View full text Add to dashboard Cite

The equine ascarids, Parascaris spp., are important nematode parasites of juvenile horses and were historically model organisms in the field of cell biology, leading to many important discoveries, and are used for the study of chromatin diminution. In veterinary parasitology, Parascaris spp. are important not only because they can cause clinical disease in young horses but also because they are the only ascarid parasites to have developed widespread anthelmintic resistance. Despite this, much of the general biology and mechanisms of anthelmintic resistance are poorly understood. This review condenses known basic biological information and knowledge on the mechanisms of anthelmintic resistance in Parascaris spp., highlighting the importance of foundational research programs. Although two variants of this parasite were recognized based on the number of chromosomes in the 1870s and suggested to be two species in 1890, one of these, P. univalens , appears to have been largely forgotten in the veterinary scientific literature over the past 100 years. We describe how this omission has had a century-long effect on nomenclature and data analysis in the field, highlighting the importance of proper specimen identification in public repositories. A summary of important basic biology, including life cycle, in vitro maintenance, and immunology, is given, and areas of future research for the improvement of knowledge and development of new systems are given. Finally, the limited knowledge regarding anthelmintic resistance in Parascaris spp. is summarized, along with caution regarding assumptions that resistance mechanisms can be applied across clades.

show abstract

Absence of Polymorphisms in Codons 167, 198 and 200 of All Seven β-Tubulin Isotypes of Benzimidazole Susceptible and Resistant Parascaris spp. Specimens from Australia

Cited by 6 publications

References 70 publications

In Silico Docking of Nematode β-Tubulins With Benzimidazoles Points to Gene Expression and Orthologue Variation as Factors in Anthelmintic Resistance

In Silico Docking of Nematode β-Tubulins With Benzimidazoles Points to Gene Expression and Orthologue Variation as Factors in Anthelmintic Resistance

Horse and donkey parasitology: differences and analogies for a correct diagnostic and management of major helminth infections

The equine ascarids: resuscitating historic model organisms for modern purposes

Contact Info

Product

Resources

About