Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity.
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.
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Amel
A
Ghouila
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia. Electronic address: fatma.guerfali@gmail.com.
Fatma Z
FZ
Guerfali
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Chiraz
C
Atri
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Aymen
A
Bali
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Hanene
H
Attia
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Rabiaa M
RM
Sghaier
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Ghada
G
Mkannez
Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Nicholas J
NJ
Dickens
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.
Dhafer
D
Laouini
D000818:Animals; D002875:Chromosomes / Q000737:chemistry*; D016054:DNA, Protozoan / Q000235:genetics; D019353:Endemic Diseases; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D023281:Genomics; D006801:Humans; D054643:INDEL Mutation; D018320:Leishmania major / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology* / Q000469:parasitology / Q000635:transmission; D051379:Mice; D008807:Mice, Inbred BALB C; D010802:Phylogeny; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014416:Tunisia / Q000453:epidemiology
D016054:DNA, Protozoan
Clinical isolates; Genomic variability; High-throughput genomic screening; Leishmania major; Severity; Zoonotic cutaneous leishmaniasis