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Genetic Analysis of Leishmania donovani Tropism Using a Naturally Attenuated Cutaneous Strain.
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- Author(s): Zhang, Wen Wei; Ramasamy, Gowthaman; McCall, Laura-Isobel; Haydock, Andrew; Ranasinghe, Shalindra; Abeygunasekara, Priyanka; Sirimanna, Ganga; Wickremasinghe, Renu; Myler, Peter; Matlashewski, Greg
- Source:
PLoS Pathogens; Jul2014, Vol. 10 Issue 7, p1-11, 11p- Subject Terms:
- Source:
- Additional Information
- 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. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of PLoS Pathogens is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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