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SELECTIVE WHOLE-GENOME AMPLIFICATION REVEALS POPULATION GENETICS OF LEISHMANIA BRAZILIENSIS DIRECTLY FROM PATIENT SKIN BIOPSIES
Genética populacional
Leishmania braziliensis
Pele do paciente
Biópsias
Author
Pilling, Olivia A.
Cunha, João L. Reis
Grace, Cooper A.
Berry, Alexander S. F.
Mitchell, Matthew W.
Yu, Jane A.
Malekshahi, Clara R.
Krespan, Elise
Go, Christina K.
Lombana, Cláudia
Song, Yun S.
Amorim, Camila F.
Lago, Alexsandro S.
Carvalho, Lucas P.
Carvalho, Edgar M.
Brisson, Dustin
Scott, Phillip
Jeffares, Daniel C.
Beiting, Daniel P.
Cunha, João L. Reis
Grace, Cooper A.
Berry, Alexander S. F.
Mitchell, Matthew W.
Yu, Jane A.
Malekshahi, Clara R.
Krespan, Elise
Go, Christina K.
Lombana, Cláudia
Song, Yun S.
Amorim, Camila F.
Lago, Alexsandro S.
Carvalho, Lucas P.
Carvalho, Edgar M.
Brisson, Dustin
Scott, Phillip
Jeffares, Daniel C.
Beiting, Daniel P.
Affilliation
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Biology. York Biomedical Research Institute. University of York. York, United Kingdom.
Department of Biology. York Biomedical Research Institute. University of York. York, United Kingdom.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Biology. School of Arts & Sciences. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Computer Science Division. University of California. Berkeley, Berkeley, California, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Computer Science Division. University of California. Berkeley, Berkeley, California, United States of America / Department of Statistics. University of California. Berkeley, California, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Department of Biology. School of Arts & Sciences. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Biology. York Biomedical Research Institute. University of York. York, United Kingdom.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Biology. York Biomedical Research Institute. University of York. York, United Kingdom.
Department of Biology. York Biomedical Research Institute. University of York. York, United Kingdom.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Biology. School of Arts & Sciences. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Computer Science Division. University of California. Berkeley, Berkeley, California, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Computer Science Division. University of California. Berkeley, Berkeley, California, United States of America / Department of Statistics. University of California. Berkeley, California, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clínicas. Salvador, BA, Brasil.
Department of Biology. School of Arts & Sciences. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Department of Biology. York Biomedical Research Institute. University of York. York, United Kingdom.
Department of Pathobiology. School of Veterinary Medicine. University of Pennsylvania. Philadelphia, Pennsylvania, United States of America.
Abstract
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.
Keywords in Portuguese
GenomaGenética populacional
Leishmania braziliensis
Pele do paciente
Biópsias
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