Genetic Analysis of Leishmania donovani Tropism Using a Naturally Attenuated Cutaneous Strain

PLoS Pathogens

Wen Wei Zhang¹  Greg Matlashewski¹  Laura-Isobel McCall¹  Renu Wickremasinghe²  Shalindra Ranasinghe²  Ganga Sirimanna³  Gowthaman Ramasamy⁴  Andrew Haydock⁴  Peter Myler⁴  Priyanka Abeygunasekara⁵ 

[1] Department of Microbiology and Immunology, McGill University, Montreal, Canada;Department of Parasitology, University of Sri Jayewardenepura, Gangodawila, Sri Lanka;Dermatology Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka;Seattle Biomedical Research Institute, Seattle, Washington, United States of America;Teaching Hospital Anuradhapura, Anuradhapura, Sri Lanka

关键词: Leishmania donovani;    Parasitic diseases;    Leishmaniasis;    Leishmania;    Mammalian genomics;    Spleen;    Promastigotes;    Amastigotes;   

DOI  :  10.1371/journal.ppat.1004244

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

A central question in Leishmania research is why most species cause cutaneous infections but others cause fatal visceral disease. Interestingly, L. donovani causes both visceral and cutaneous leishmaniasis in Sri Lanka. L. donovani clinical isolates were therefore obtained from cutaneous leishmaniasis (CL-SL) and visceral leishmaniasis (VL-SL) patients from Sri Lanka. The CL-SL isolate was severely attenuated compared to the VL-SL isolate for survival in visceral organs in BALB/c mice. Genomic and transcriptomic analysis argue that gene deletions or pseudogenes specific to CL-SL are not responsible for the difference in disease tropism and that single nucleotide polymorphisms (SNPs) and/or gene copy number variations play a major role in altered pathology. This is illustrated through the observations within showing that a decreased copy number of the A2 gene family and a mutation in the ras-like RagC GTPase enzyme in the mTOR pathway contribute to the attenuation of the CL-SL strain in visceral infection. Overall, this research provides a unique perspective on genetic differences associated with diverse pathologies caused by Leishmania infection.

【 授权许可】

CC BY