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Genetics and Genomics of Leishmania
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Genetics and Genomics of Leishmania

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (20 September 2022) | Viewed by 8807

Special Issue Editors

Dr. Begoña Aguado

E-Mail Website
Guest Editor
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain
Interests: genomics; transcriptomics; proteomics; Leishmania; omics; massive data analysis
Dr. Jose M. Requena

E-Mail Website
Guest Editor
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain
Interests: Leishmania; gene expression; genomics; transcriptomics; proteomics; heat shock proteins; RNA binding proteins; phylogenetics; trypanosomatids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parasites of the genus Leishmania are well-known as causative agents of leishmaniasis, a group of diseases affecting millions of persons living in tropical and subtropical regions. There is currently no acceptable vaccine for humans, and treatment options are limited (low number of drugs and with high toxicity). Efforts are needed to find better low toxicity drugs and to elucidate resistance mechanisms that preclude efficiency of current available ones. In addition, our understanding of the Leishmania virulence factors responsible for these diseases is limited. Integrated research into the molecular biology of these pathogens is needed to establish how these parasites infect, replicate, and are transmitted to new hosts.

In the past fifteen years, great progress has been made in our understanding of Leishmania. The advent of high-throughput technologies has led to the accumulation of a massive amount of genomic data. Now, it is time to integrate this information, together with studies dealing with transcriptomics and proteomics analyses, to decipher particularities in the molecular mechanisms and biosynthetic pathways of this parasite. This knowledge will contribute to designing new strategies to combat these devastating diseases.

This Special Issue welcomes original research articles dealing with topics around the genetics, genomics, transcriptomics, and proteomics of Leishmania parasites. Studies focusing on pathogen–host interactions, traits of drug resistance, phylogenetics, and evolution of these organisms are also within the scope of this Special Issue. Additionally, review articles are welcome which cover the current literature and present a synthesis of our current knowledge of these pathogens and the genetic processes that make them successful.

Dr. Begoña Aguado
Dr. Jose M. Requena
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. Genes 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 2600 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

  • Gene expression mechanisms and methods
  • Genomics
  • Transcriptomics studies
  • Proteomics analysis
  • Drugs resistance mechanisms
  • Species-specific genes
  • Metabolic enzymes
  • Phylogenetic and phylogenomic analyses
  • Evolution
  • Leishmania-related organisms

Published Papers (3 papers)

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Research

17 pages, 2730 KiB  
Article
An RNA Interference (RNAi) Toolkit and Its Utility for Functional Genetic Analysis of Leishmania (Viannia)
by Lon-Fye Lye, Katherine L. Owens, Soojin Jang, Joseph E. Marcus, Erin A. Brettmann and Stephen M. Beverley
Genes 2023, 14(1), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/genes14010093 - 28 Dec 2022
Cited by 2 | Viewed by 1752
Abstract
RNA interference (RNAi) is a powerful tool whose efficacy against a broad range of targets enables functional genetic tests individually or systematically. However, the RNAi pathway has been lost in evolution by a variety of eukaryotes including most Leishmania sp. RNAi was retained [...] Read more.
RNA interference (RNAi) is a powerful tool whose efficacy against a broad range of targets enables functional genetic tests individually or systematically. However, the RNAi pathway has been lost in evolution by a variety of eukaryotes including most Leishmania sp. RNAi was retained in species of the Leishmania subgenus Viannia, and here we describe the development, optimization, and application of RNAi tools to the study of L. (Viannia) braziliensis (Lbr). We developed vectors facilitating generation of long-hairpin or “stem-loop” (StL) RNAi knockdown constructs, using GatewayTM site-specific recombinase technology. A survey of applications of RNAi in L. braziliensis included genes interspersed within multigene tandem arrays such as quinonoid dihydropteridine reductase (QDPR), a potential target or modulator of antifolate sensitivity. Other tests include genes involved in cell differentiation and amastigote proliferation (A600), and essential genes of the intraflagellar transport (IFT) pathway. We tested a range of stem lengths targeting the L. braziliensis hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and reporter firefly luciferase (LUC) genes and found that the efficacy of RNAi increased with stem length, and fell off greatly below about 128 nt. We used the StL length dependency to establish a useful ‘hypomorphic’ approach not possible with other gene ablation strategies, with shorter IFT140 stems yielding viable cells with compromised flagellar morphology. We showed that co-selection for RNAi against adenine phosphoryl transferase (APRT1) using 4-aminopyrazolpyrimidine (APP) could increase the efficacy of RNAi against reporter constructs, a finding that may facilitate improvements in future work. Thus, for many genes, RNAi provides a useful tool for studying Leishmania gene function with some unique advantages. Full article
(This article belongs to the Special Issue Genetics and Genomics of Leishmania)
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22 pages, 7376 KiB  
Article
Gene Annotation and Transcriptome Delineation on a De Novo Genome Assembly for the Reference Leishmania major Friedlin Strain
by Esther Camacho, Sandra González-de la Fuente, Jose C. Solana, Alberto Rastrojo, Fernando Carrasco-Ramiro, Jose M. Requena and Begoña Aguado
Genes 2021, 12(9), 1359; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091359 - 29 Aug 2021
Cited by 9 | Viewed by 2492
Abstract
Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The [...] Read more.
Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The objective was successfully attained in 2005, and this represented a milestone for Leishmania molecular biology studies around the world. Although the LmjF genome sequence was done following a shotgun strategy and using classical Sanger sequencing, the results were excellent, and this genome assembly served as the reference for subsequent genome assemblies in other Leishmania species. Here, we present a new assembly for the genome of this strain (named LMJFC for clarity), generated by the combination of two high throughput sequencing platforms, Illumina short-read sequencing and PacBio Single Molecular Real-Time (SMRT) sequencing, which provides long-read sequences. Apart from resolving uncertain nucleotide positions, several genomic regions were reorganized and a more precise composition of tandemly repeated gene loci was attained. Additionally, the genome annotation was improved by adding 542 genes and more accurate coding-sequences defined for around two hundred genes, based on the transcriptome delimitation also carried out in this work. As a result, we are providing gene models (including untranslated regions and introns) for 11,238 genes. Genomic information ultimately determines the biology of every organism; therefore, our understanding of molecular mechanisms will depend on the availability of precise genome sequences and accurate gene annotations. In this regard, this work is providing an improved genome sequence and updated transcriptome annotations for the reference L. major Friedlin strain. Full article
(This article belongs to the Special Issue Genetics and Genomics of Leishmania)
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20 pages, 1107 KiB  
Article
Genome Analysis of Endotrypanum and Porcisia spp., Closest Phylogenetic Relatives of Leishmania, Highlights the Role of Amastins in Shaping Pathogenicity
by Amanda T. S. Albanaz, Evgeny S. Gerasimov, Jeffrey J. Shaw, Jovana Sádlová, Julius Lukeš, Petr Volf, Fred R. Opperdoes, Alexei Y. Kostygov, Anzhelika Butenko and Vyacheslav Yurchenko
Genes 2021, 12(3), 444; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12030444 - 20 Mar 2021
Cited by 10 | Viewed by 3591
Abstract
While numerous genomes of Leishmania spp. have been sequenced and analyzed, an understanding of the evolutionary history of these organisms remains limited due to the unavailability of the sequence data for their closest known relatives, Endotrypanum and Porcisia spp., infecting sloths and porcupines. [...] Read more.
While numerous genomes of Leishmania spp. have been sequenced and analyzed, an understanding of the evolutionary history of these organisms remains limited due to the unavailability of the sequence data for their closest known relatives, Endotrypanum and Porcisia spp., infecting sloths and porcupines. We have sequenced and analyzed genomes of three members of this clade in order to fill this gap. Their comparative analyses revealed only minute differences from Leishmaniamajor genome in terms of metabolic capacities. We also documented that the number of genes under positive selection on the Endotrypanum/Porcisia branch is rather small, with the flagellum-related group of genes being over-represented. Most significantly, the analysis of gene family evolution revealed a substantially reduced repertoire of surface proteins, such as amastins and biopterin transporters BT1 in the Endotrypanum/Porcisia species when compared to amastigote-dwelling Leishmania. This reduction was especially pronounced for δ-amastins, a subfamily of cell surface proteins crucial in the propagation of Leishmania amastigotes inside vertebrate macrophages and, apparently, dispensable for Endotrypanum/Porcisia, which do not infect such cells. Full article
(This article belongs to the Special Issue Genetics and Genomics of Leishmania)
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