Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain.
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 leishmanias...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-07-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4081786?pdf=render |
| _version_ | 1819075977993519104 |
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| author | Wen Wei Zhang Gowthaman Ramasamy Laura-Isobel McCall Andrew Haydock Shalindra Ranasinghe Priyanka Abeygunasekara Ganga Sirimanna Renu Wickremasinghe Peter Myler Greg Matlashewski |
| author_facet | Wen Wei Zhang Gowthaman Ramasamy Laura-Isobel McCall Andrew Haydock Shalindra Ranasinghe Priyanka Abeygunasekara Ganga Sirimanna Renu Wickremasinghe Peter Myler Greg Matlashewski |
| author_sort | Wen Wei Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:33:59Z |
| format | Article |
| id | doaj.art-b8524135859c4f919a2f31d9512a5d6d |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T18:33:59Z |
| publishDate | 2014-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b8524135859c4f919a2f31d9512a5d6d2022-12-21T18:54:12ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-07-01107e100424410.1371/journal.ppat.1004244Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain.Wen Wei ZhangGowthaman RamasamyLaura-Isobel McCallAndrew HaydockShalindra RanasinghePriyanka AbeygunasekaraGanga SirimannaRenu WickremasinghePeter MylerGreg MatlashewskiA 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.http://europepmc.org/articles/PMC4081786?pdf=render |
| spellingShingle | Wen Wei Zhang Gowthaman Ramasamy Laura-Isobel McCall Andrew Haydock Shalindra Ranasinghe Priyanka Abeygunasekara Ganga Sirimanna Renu Wickremasinghe Peter Myler Greg Matlashewski Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. PLoS Pathogens |
| title | Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. |
| title_full | Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. |
| title_fullStr | Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. |
| title_full_unstemmed | Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. |
| title_short | Genetic analysis of Leishmania donovani tropism using a naturally attenuated cutaneous strain. |
| title_sort | genetic analysis of leishmania donovani tropism using a naturally attenuated cutaneous strain |
| url | http://europepmc.org/articles/PMC4081786?pdf=render |
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