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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Veröffentlicht in:PLoS pathogens 2023-03, Vol.19 (3), p.e1011230
Hauptverfasser: Pilling, Olivia A, Reis-Cunha, João L, 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
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container_issue 3
container_start_page e1011230
container_title PLoS pathogens
container_volume 19
creator Pilling, Olivia A
Reis-Cunha, João L
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
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.
doi_str_mv 10.1371/journal.ppat.1011230
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subjects Amplification
Analysis
Biology and Life Sciences
Biopsy
Brazil
Care and treatment
Computer and Information Sciences
Cutaneous leishmaniasis
Design
Diagnosis
Drug resistance
Experimental infection
Failure rates
Gene amplification
Genetic aspects
Genetics
Genetics, Population
Genome, Protozoan - genetics
Genomes
Genomics
Health aspects
Health services
Humans
Infections
Leishmania
Leishmania braziliensis
Leishmania braziliensis - genetics
Leishmaniasis
Leishmaniasis, Cutaneous - parasitology
Medical research
Medicine and Health Sciences
Medicine, Experimental
Parasites
Parasitic diseases
Parasitology - methods
Patients
People and places
Phenotypes
Population genetics
Skin
Skin - parasitology
Tropical diseases
Vector-borne diseases
title Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies
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