Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain.

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Zhang WW,Ramasamy G,McCall LI,Haydock A,Ranasinghe S,Abeygunasekara P,Sirimanna G,Wickremasinghe R,Myler P,Matlashewski G

doi

10.1371/journal.ppat.1004244

subject

Has Abstract

pub_date

2014-07-03 00:00:00

pages

e1004244

issue

7

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-14-00089

journal_volume

10

pub_type

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