scholarly journals Advances in the Molecular and Cellular Biology of Strongyloides spp.

2019 ◽  
Vol 6 (4) ◽  
pp. 161-178 ◽  
Author(s):  
Tegegn G. Jaleta ◽  
James B. Lok

Abstract Purpose of Review This paper constitutes an update of recent studies on the general biology, molecular genetics, and cellular biology of Strongyloides spp. and related parasitic nematodes. Recent Findings Increasingly, human strongyloidiasis is considered the most neglected of neglected tropical diseases. Despite this, the last 5 years has seen remarkable advances in the molecular biology of Strongyloides spp. Genome sequences for S. stercoralis, S. ratti, S. venezuelensis, S. papillosus, and the related parasite Parastrongyloides trichosuri were created, annotated, and analyzed. These genomic resources, along with a practical transgenesis platform for Strongyloides spp., aided a major achievement, the advent of targeted mutagenesis via CRISPR/Cas9 in S. stercoralis and S. ratti. The genome sequences have also enabled significant molecular epidemiologic and phylogenetic findings on human strongyloidiasis, including the first genetic evidence of zoonotic transmission of S. stercoralis between dogs and humans. Studies of molecular signaling pathways identified the nuclear receptor Ss-DAF-12 as one that can be manipulated in the parasite by exogenous application of its steroid ligands. The chemotherapeutic implications of this were unscored by a study in which a Ss-DAF-12 ligand suppressed autoinfection by S. stercoralis in a new murine model of human strongyloidiasis. Summary Seminal advances in genomics of Strongyloides spp. have transformed research into strongyloidiasis, facilitating fundamental phylogenetic and epidemiologic studies and aiding the deployment of CRISPR/Cas9 gene disruption and editing as functional genomic tools in Strongyloides spp. Studies of Ss-DAF-12 signaling in S. stercoralis demonstrated the potential of this pathway as a novel chemotherapeutic target in parasitic nematodes.

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 67 ◽  
Author(s):  
Cristiane C Thompson ◽  
Vanessa E Emmel ◽  
Erica L Fonseca ◽  
Michel A Marin ◽  
Ana Carolina P Vicente

The identification of the clinically relevant viridans streptococci group, at species level, is still problematic. The aim of this study was to extract taxonomic information from the complete genome sequences of 67 streptococci, comprising 19 species, by means of genomic analyses, multilocus sequence analysis (MLSA), average amino acid identity (AAI), genomic signatures, genome-to-genome distances (GGD) and codon usage bias. We then attempted to determine the usefulness of these genomic tools for species identification in streptococci. Our results showed that MLSA, AAI and GGD analyses are robust markers to identify streptococci at the species level, for instance,S. pneumoniae,S. mitis, andS. oralis. AStreptococcusspecies can be defined as a group of strains that share ≥ 95% DNA similarity in MLSA and AAI, and > 70% DNA identity in GGD. This approach allows an advanced understanding of bacterial diversity.


2021 ◽  
Vol 17 (7) ◽  
pp. e1009682
Author(s):  
Jürgen Krücken ◽  
Lindy Holden-Dye ◽  
Jennifer Keiser ◽  
Roger K. Prichard ◽  
Simon Townson ◽  
...  

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer–DNDi partnership is an outstanding example of “One World Health,” in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.


2004 ◽  
Vol 31 (6) ◽  
pp. 563 ◽  
Author(s):  
A. Harvey Millar

Knowledge of cellular compartmentation is critical to an understanding of many aspects of biological function in plant cells but it remains an under-emphasised concept in the use of and investment in plant functional genomic tools. The emerging effort in plant subcellular proteomics is discussed, and the current datasets that are available for a series of organelles and cellular membranes isolated from a range of plant species are noted. The benefit of knowing subcellular location in determining the role of proteins of unknown function is considered alongside the challenges faced in this endeavour. These include clear problems in dealing with contamination during the isolation of subcellular compartments, the meaningful integration of these datasets once completed to assemble a jigsaw of the cellular proteome as a whole, and the use of the wider literature in supplementing this proteomic discovery effort.


2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Sergey V. Tarlachkov ◽  
Irina P. Starodumova ◽  
Lubov V. Dorofeeva ◽  
Natalia V. Prisyazhnaya ◽  
Tatiana V. Roubtsova ◽  
...  

ABSTRACT Draft genome sequences of 28 strains of Microbacteriaceae from plants infested by plant-parasitic nematodes were obtained using Illumina technology. The sequence data will provide useful baseline information for the development of comparative genomics and systematics of Microbacteriaceae and facilitate understanding of molecular mechanisms involved in interactions between plants and nematode-associated bacterial complexes.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Traini ◽  
Massimo Iorizzo ◽  
Harpartap Mann ◽  
James M. Bradeen ◽  
Domenico Carputo ◽  
...  

Tuber-bearing potato species possess several genes that can be exploited to improve the genetic background of the cultivated potatoSolanum tuberosum. Among them,S. bulbocastanumandS. commersoniiare well known for their strong resistance to environmental stresses. However, scant information is available for these species in terms of genome organization, gene function, and regulatory networks. Consequently, genomic tools to assist breeding are meager, and efficient exploitation of these species has been limited so far. In this paper, we employed the reference genome sequences from cultivated potato and tomato and a collection of sequences of 1,423 potato Diversity Arrays Technology (DArT) markers that show polymorphic representation across the genomes ofS. bulbocastanumand/orS. commersoniigenotypes. Our results highlighted microscale genome sequence heterogeneity that may play a significant role in functional and structural divergence between related species. Our analytical approach provides knowledge of genome structural and sequence variability that could not be detected by transcriptome and proteome approaches.


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