Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies.
In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome...
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011230 |
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| author | Olivia A Pilling João L Reis-Cunha Cooper A Grace Alexander S F Berry Matthew W Mitchell Jane A Yu Clara R Malekshahi Elise Krespan Christina K Go Cláudia Lombana Yun S Song Camila F Amorim Alexsandro S Lago Lucas P Carvalho Edgar M Carvalho Dustin Brisson Phillip Scott Daniel C Jeffares Daniel P Beiting |
| author_facet | Olivia A Pilling João L Reis-Cunha Cooper A Grace Alexander S F Berry Matthew W Mitchell Jane A Yu Clara R Malekshahi Elise Krespan Christina K Go Cláudia Lombana Yun S Song Camila F Amorim Alexsandro S Lago Lucas P Carvalho Edgar M Carvalho Dustin Brisson Phillip Scott Daniel C Jeffares Daniel P Beiting |
| author_sort | Olivia A Pilling |
| collection | DOAJ |
| description | In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes. |
| format | Article |
| id | doaj-art-737717bbee8b47e590ec22cd8859a3a4 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-737717bbee8b47e590ec22cd8859a3a42025-08-20T03:57:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-03-01193e101123010.1371/journal.ppat.1011230Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies.Olivia A PillingJoão L Reis-CunhaCooper A GraceAlexander S F BerryMatthew W MitchellJane A YuClara R MalekshahiElise KrespanChristina K GoCláudia LombanaYun S SongCamila F AmorimAlexsandro S LagoLucas P CarvalhoEdgar M CarvalhoDustin BrissonPhillip ScottDaniel C JeffaresDaniel P BeitingIn Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.https://doi.org/10.1371/journal.ppat.1011230 |
| spellingShingle | Olivia A Pilling João L Reis-Cunha Cooper A Grace Alexander S F Berry Matthew W Mitchell Jane A Yu Clara R Malekshahi Elise Krespan Christina K Go Cláudia Lombana Yun S Song Camila F Amorim Alexsandro S Lago Lucas P Carvalho Edgar M Carvalho Dustin Brisson Phillip Scott Daniel C Jeffares Daniel P Beiting Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. PLoS Pathogens |
| title | Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. |
| title_full | Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. |
| title_fullStr | Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. |
| title_full_unstemmed | Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. |
| title_short | Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. |
| title_sort | selective whole genome amplification reveals population genetics of leishmania braziliensis directly from patient skin biopsies |
| url | https://doi.org/10.1371/journal.ppat.1011230 |
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