Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity
| Autor: | Amel Ghouila, Dhafer Laouini, Chiraz Atri, Hanène Attia, Ghada Mkannez, Rabiaa M. Sghaier, Nicholas J. Dickens, Aymen Bali, Fatma Z. Guerfali |
|---|---|
| Přispěvatelé: | Université de Tunis El Manar (UTM), Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Réseau International des Instituts Pasteur (RIIP), This work was funded as part of LeiSHield consortium by contribution of the Institut Pasteur International Direction and was partly supported by a NIAID/NIH Grant Number 5P50AI074178 and by Wellcome Trust (104111) Core Funding for the WTCMP., We are grateful to Prof. Afif Ben Salah, Mr Adel Gharbi and Mr Amor Zaatour for kindly providing us with L. major isolates from the field, all members of the Medical Epidemiology team in Institut Pasteur de Tunis for collecting these isolates and for the follow-up of lesions sizes and data collection, and the Tunisian patients for their kind help and consent. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MESH: Leishmania major/genetics MESH: Leishmaniasis Cutaneous/transmission Endemic Diseases Gene Dosage Disease MESH: Tunisia/epidemiology Severity of Illness Index MESH: INDEL Mutation Mice INDEL Mutation Genomic variability Leishmania major MESH: Animals Copy-number variation Phylogeny MESH: Phylogeny Genetics Mice Inbred BALB C MESH: Polymorphism Single Nucleotide MESH: Genomics MESH: Gene Dosage Genomics MESH: Follow-Up Studies MESH: Chromosomes/chemistry 3. Good health MESH: Endemic Diseases Phylogeography MESH: Leishmania major/classification Infectious Diseases [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology MESH: Phylogeography Female Microbiology (medical) Tunisia MESH: Leishmaniasis Cutaneous/epidemiology MESH: Mice Inbred BALB C Leishmaniasis Cutaneous Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Microbiology Article Chromosomes Severity 03 medical and health sciences Cutaneous leishmaniasis High-throughput genomic screening MESH: Severity of Illness Index medicine Animals Humans Indel Molecular Biology MESH: Mice Ecology Evolution Behavior and Systematics Comparative genomics Clinical isolates MESH: Leishmaniasis Cutaneous/parasitology MESH: Humans DNA Protozoan MESH: DNA Protozoan/genetics medicine.disease Leishmania biology.organism_classification MESH: Leishmania major/isolation & purification 030104 developmental biology MESH: Female Zoonotic cutaneous leishmaniasis [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Follow-Up Studies |
| Zdroj: | Infection, Genetics and Evolution Infection, Genetics and Evolution, Elsevier, 2017, 50, pp.110-120. ⟨10.1016/j.meegid.2016.10.029⟩ |
| ISSN: | 1567-1348 1567-7257 |
| Popis: | International audience; Zoonotic cutaneous leishmaniasis caused by Leishmania (L.) major parasites affects urban and suburban areas in the center and south of Tunisia where the disease is endemo-epidemic. Several cases were reported in human patients for which infection due to L major induced lesions with a broad range of severity. However, very little is known about the mechanisms underlying this diversity. Our hypothesis is that parasite genomic variability could, in addition to the host immunological background, contribute to the intra-species clinical variability observed in patients and explain the lesion size differences observed in the experimental model. Based on several epidemiological, in vivo and in vitro experiments, we focused on two clinical isolates showing contrasted severity in patients and BALB/c experimental mice model. We used DNA-seq as a high-throughput technology to facilitate the identification of genetic variants with discriminating potential between both isolates. Our results demonstrate that various levels of heterogeneity could be found between both L major isolates in terms of chromosome or gene copy number variation (CNV), and that the intra-species divergence could surprisingly be related to single nucleotide polymorphisms (SNPs) and Insertion/Deletion (InDels) events. Interestingly, we particularly focused here on genes affected by both types of variants and correlated them with the observed gene CNV. Whether these differences are sufficient to explain the severity in patients is obviously still open to debate, but we do believe that additional layers of -omic information is needed to complement the genomic screen in order to draw a more complete map of severity determinants. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect