Intra-Specific Diversity of Leishmania major Isolates: A Key Determinant of Tunisian Zoonotic Cutaneous Leishmaniasis Clinical Polymorphism.

Hanene Attia,Adel Gharbi,Dhafer Laouini,Chiraz Atri,Afif Ben-Salah,Manel Sghaier,Nabil Belhaj-Hamida,Aymen Bali,Fatma Guerfali,Sadok Chlif,Amor Zaatour,Koussay Dellagi

doi:10.3390/microorganisms10030505

Abstract

The clinical expression of zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major parasites has a broad spectrum ranging from asymptomatic infection to self-limited cutaneous sores or severe disease. In concert with the host immune responses, the vector variability and the number of bites, genetic variation between L. major isolates might impact on the clinical output of the disease. We investigated herein the intra-specific variability of L. major field isolates independently of host or vector factors and then tried to correlate parasite variability to ZCL severity in corresponding patients. Several assays were applied, i.e., in vivo pathogenicity of promastigotes in a BALB/c mice model, resistance/sensibility to complement lysis, in vitro growth kinetics, and expression of different lectins on the promastigote surface. Combining all these parameters allowed us to conclude that the resistance to complement lysis and PNA/Jacalin lectins binding to parasite surfaces are important markers of parasite virulence. These factors correlate significantly with clinic polymorphism of ZCL and modestly with genetic micro-heterogeneity, a characteristic we previously revealed with a MLMT profile.

Highlights

Introduction iationsAbout 20 Leishmania (L.) species are considered as pathogens for humans and cause a group of diseases known as leishmaniasis [1]
We previously reported, using multi-locus microsatellite typing (MLMT) with 10 highly informative and discriminative markers, the genetic structure of Tunisian L. major isolates collected from patients living in different old and emerging foci of Central Tunisia [8]
In order to study the intra-specific variability of L. major, as one of the key factors of zoonotic cutaneous leishmaniasis (ZCL) clinical polymorphism and virulence, we report here the experimental pathogenicity in a BALB/c mouse model, the in vitro resistance to complement lysis, the in vitro growth kinetics, and the expression of carbohydrates on the parasite surface of 18 Tunisian L. major isolates obtained from the field, and correlated the results to their clinical manifestation in human patients from whom they were isolated

Summary

Introduction

About 20 Leishmania (L.) species are considered as pathogens for humans and cause a group of diseases known as leishmaniasis [1]. Different clinical manifestations of CL caused by the same Leishmania species have been described. Uncommon lesions caused by L. major reported in Sudan are difficult to recognize as Leishmania infection and are difficult to treat [2]. In Iran, CL cases caused by L. major were reported as polymorphic. The clinical presentation of cases varied from typical lesions to atypical ones including erythematous volcanic ulcers, multi-infections, lupoid, diffuse, eczematous, verrucous, dry, and nodular lesions [3]. In Tunisia, L. major is the most prevalent dermotropic Leishmania species and causes zoonotic cutaneous leishmaniasis (ZCL) [4]. It is a polymorphic disease, even within a small endemic focus, with various

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