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Pathogens
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Helminths, Anthelmintics and Anthelmintic Resistance
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Helminths, Anthelmintics and Anthelmintic Resistance

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (10 March 2023) | Viewed by 9804

Special Issue Editors

Dr. Rahul Tyagi

E-Mail Website
Guest Editor
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, 4523 Clayton Ave., St. Louis, MO 63110, USA
Interests: helminths; nematode; parasitism; computational genomics; multi-omics data; RNA biology
Dr. Mostafa Elfawal

E-Mail Website
Guest Editor
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Interests: parasitology; nematology; soil transmitted nematodes; anthelmintics; drug screening; target validation; host parasite interaction

Special Issue Information

Dear Colleagues,

Helminth parasites are among the most prevalent disease-causing agents of human, livestock and companion animals. These parasites have a dramatic impact on the global economy and together perpetuate the poverty cycle via its harmful impact on human well-being, notably hundreds of millions of children and pregnant women. The cost and losses associated with parasitic nematodes of livestock are estimated to be tens of billions of dollars worldwide, due to adverse effects on health and productivity. These parasites (parasitic nematodes and platyhelminthes) together infect over two billion people worldwide, mostly in tropical countries, resulting in mortality, severe morbidity, a reduced workforce, and heavy socioeconomic burdens on humans. Since helminthiases are predominantly diseases of poverty, research into helminth biology and therapeutics has historically been neglected, as a result of which WHO has included many of these among its list of neglected tropical diseases (NTDs). Given the diversity of these pathogens, the majority of existing drugs have narrow efficacy profiles, with only a single existing drug class approved and found to be effective for a set of related worms. This has further enhanced the concerns of emerging drug resistance in human parasites, following the footsteps of those infected livestock and almost resistant to all veterinary anthelmintics.

Since the beginning of the millennium, and especially over the last decade, the characterization of many helminth genomes has expanded the knowledge base that is essential for accelerating basic and translational research. This, along with continuous development in various relevant assays and drug screening, has tangibly accelerated the pace of progress towards novel anthelmintic classes. It is now possible to imagine that, contingent on continuous support by various funding agencies worldwide, over the coming decade, the helminth research community could make big strides towards a better understanding of helminth biology, identifying and developing active and broadly effective drugs and other interventions to treat and control these important parasites.

This will inevitably require the coming together of the relatively small helminth community, with varied skills to collaborate and effectively communicate their insights to each other. In light of this, Pathogens is preparing to publish a Special Issue devoted to “Helminths, Anthelmintics and Anthelmintic Resistance”. Our principal aim is to publish the most innovative, novel results and insights obtained by outstanding research teams working in this field. We also welcome useful review articles summarizing the field, or recent insights related to a relevant theme.

Dr. Rahul Tyagi
Dr. Mostafa Elfawal
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • helminths
  • anthelmintics
  • anthelmintic resistance
  • soil-transmitted helminths
  • schistosomiasis
  • parasitic nematodes
  • filariasis
  • helminth genomics
  • host-parasite interaction

Published Papers (4 papers)

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Research

20 pages, 939 KiB  
Article
Excretory/Secretory Proteome of Females and Males of the Hookworm Ancylostoma ceylanicum
by Samuel C. Uzoechi, Bruce A. Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K. Bracken, Paul J. Brindley, R. Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M. Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic and Makedonka Mitreva
Pathogens 2023, 12(1), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010095 - 06 Jan 2023
Cited by 1 | Viewed by 2584
Abstract
The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and [...] Read more.
The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in female and male ESPs, respectively, using this improved version, identifying a total of 795 ESPs (70% in both sexes, with the remaining sex-specific). Using functional databases (KEGG, GO and Interpro), common and sex-specific enriched functions were identified. Comparisons with the exclusively human-infective hookworm Necator americanus identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male A. ceylanicum. The findings provide a deeper understanding of hookworm protein functions that assure long-term host survival and facilitate future engineering of transgenic hookworms and analysis of regulatory elements mediating the high-level expression of ESPs. Furthermore, the findings expand the list of potential vaccine and diagnostic targets and identify biologics that can be explored for anti-inflammatory potential. Full article
(This article belongs to the Special Issue Helminths, Anthelmintics and Anthelmintic Resistance)
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16 pages, 2619 KiB  
Article
Identification of Novel Genes and Proteoforms in Angiostrongylus costaricensis through a Proteogenomic Approach
by Esdras Matheus Gomes da Silva, Karina Mastropasqua Rebello, Young-Jun Choi, Vitor Gregorio, Alexandre Rossi Paschoal, Makedonka Mitreva, James H. McKerrow, Ana Gisele da Costa Neves-Ferreira and Fabio Passetti
Pathogens 2022, 11(11), 1273; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11111273 - 31 Oct 2022
Cited by 2 | Viewed by 1571
Abstract
RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- [...] Read more.
RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions. Angiostrongylus costaricensis is a roundworm species that causes an intestinal inflammatory disease, known as abdominal angiostrongyliasis (AA). Currently, there is no drug available that acts directly on this parasite, mostly due to the sparse understanding of its molecular characteristics. The available genome of A. costaricensis, specific to the Costa Rica strain, is a draft version that is not supported by transcript- or protein-level evidence. This study used RNA-Seq and MS/MS data to perform an in-depth annotation of the A. costaricensis genome. Our prediction improved the reference annotation with (a) novel coding and non-coding genes; (b) pieces of evidence of alternative splicing generating new proteoforms; and (c) a list of SNVs between the Brazilian (Crissiumal) and the Costa Rica strain. To the best of our knowledge, this is the first time that a multi-omics approach has been used to improve the genome annotation of A. costaricensis. We hope this improved genome annotation can assist in the future development of drugs, kits, and vaccines to treat, diagnose, and prevent AA caused by either the Brazil strain (Crissiumal) or the Costa Rica strain. Full article
(This article belongs to the Special Issue Helminths, Anthelmintics and Anthelmintic Resistance)
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17 pages, 3151 KiB  
Article
Aspartyl Protease Inhibitors as Anti-Filarial Drugs
by Liana Beld, Hyeim Jung, Christina A. Bulman, Bruce A. Rosa, Peter U. Fischer, James W. Janetka, Sara Lustigman, Judy A. Sakanari and Makedonka Mitreva
Pathogens 2022, 11(6), 707; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11060707 - 18 Jun 2022
Cited by 4 | Viewed by 2377
Abstract
The current treatments for lymphatic filariasis and onchocerciasis do not effectively kill the adult parasitic nematodes, allowing these chronic and debilitating diseases to persist in millions of people. Thus, the discovery of new drugs with macrofilaricidal potential to treat these filarial diseases is [...] Read more.
The current treatments for lymphatic filariasis and onchocerciasis do not effectively kill the adult parasitic nematodes, allowing these chronic and debilitating diseases to persist in millions of people. Thus, the discovery of new drugs with macrofilaricidal potential to treat these filarial diseases is critical. To facilitate this need, we first investigated the effects of three aspartyl protease inhibitors (APIs) that are FDA-approved as HIV antiretroviral drugs on the adult filarial nematode, Brugia malayi and the endosymbiotic bacteria, Wolbachia. From the three hits, nelfinavir had the best potency with an IC50 value of 7.78 µM, followed by ritonavir and lopinavir with IC50 values of 14.3 µM and 16.9 µM, respectively. The three APIs have a direct effect on killing adult B. malayi after 6 days of exposure in vitro and did not affect the Wolbachia titers. Sequence conservation and stage-specific gene expression analysis identified Bm8660 as the most likely primary aspartic protease target for these drug(s). Immunolocalization using antibodies raised against the Bm8660 ortholog of Onchocerca volvulus showed it is strongly expressed in female B. malayi, especially in metabolically active tissues such as lateral and dorsal/ventral chords, hypodermis, and uterus tissue. Global transcriptional response analysis using adult female B. pahangi treated with APIs identified four additional aspartic proteases differentially regulated by the three effective drugs, as well as significant enrichment of various pathways including ubiquitin mediated proteolysis, protein kinases, and MAPK/AMPK/FoxO signaling. In vitro testing against the adult gastro-intestinal nematode Trichuris muris suggested broad-spectrum potential for these APIs. This study suggests that APIs may serve as new leads to be further explored for drug discovery to treat parasitic nematode infections. Full article
(This article belongs to the Special Issue Helminths, Anthelmintics and Anthelmintic Resistance)
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12 pages, 2777 KiB  
Article
The Differences in the Susceptibility Patterns to Triclabendazole Sulfoxide in Field Isolates of Fasciola hepatica Are Associated with Geographic, Seasonal, and Morphometric Variations
by Martha V. Fernandez-Baca, Cristian Hoban, Rodrigo A. Ore, Pedro Ortiz, Young-Jun Choi, César Murga-Moreno, Makedonka Mitreva and Miguel M. Cabada
Pathogens 2022, 11(6), 625; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11060625 - 28 May 2022
Cited by 2 | Viewed by 2194
Abstract
Triclabendazole (TCBZ) resistance is an emerging problem in fascioliasis that is not well understood. Studies including small numbers of parasites fail to capture the complexity of susceptibility variations between and within Fasciolahepatica populations. As the first step to studying the complex resistant [...] Read more.
Triclabendazole (TCBZ) resistance is an emerging problem in fascioliasis that is not well understood. Studies including small numbers of parasites fail to capture the complexity of susceptibility variations between and within Fasciolahepatica populations. As the first step to studying the complex resistant phenotype–genotype associations, we characterized a large sample of adult F. hepatica with diverging TCBZ susceptibility. We collected parasites from naturally infected livestock slaughtered in the Cusco and Cajamarca regions of Peru. These parasites were exposed to TCBZ sulfoxide (TCBZ.SO) in vitro to determine their susceptibility. We used a motility score to determine the parasite’s viability. We titrated drug concentrations and times to detect 20% non-viable (susceptible conditions) or 80% non-viable (resistant conditions) parasites. We exposed 3348 fully motile parasites to susceptible (n = 1565) or resistant (n = 1783) conditions. Three hundred and forty-one (21.8%) were classified as susceptible and 462 (25.9%) were classified as resistant. More resistant parasites were found in Cusco than in Cajamarca (p < 0.001). Resistant parasites varied by slaughterhouse (p < 0.001), month of the year (p = 0.008), fluke length (p = 0.016), and year of collection (p < 0.001). The in vitro susceptibility to TCBZ.SO in wildtype F. hepatica was associated with geography, season, and morphometry. Full article
(This article belongs to the Special Issue Helminths, Anthelmintics and Anthelmintic Resistance)
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