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...
Gespeichert in:
Veröffentlicht in: | PLoS pathogens 2023-03, Vol.19 (3), p.e1011230 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
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 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2802052940</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A744741150</galeid><doaj_id>oai_doaj_org_article_737717bbee8b47e590ec22cd8859a3a4</doaj_id><sourcerecordid>A744741150</sourcerecordid><originalsourceid>FETCH-LOGICAL-c662t-a01564d087035a5da7efd97599f9790ba6e64c38220558a8e6f183e029170c043</originalsourceid><addsrcrecordid>eNqVkk-P0zAQxSMEYpeFb4DAEhc4tNhxHDsntFrxp1IFEgtna-JMWhcnDnZaWC58dVyaXW3RXlAOica_eeP3Mln2lNE545K93vht6MHNhwHGOaOM5Zzey06ZEHwmuSzu3_o-yR7FuKG0YJyVD7MTXlYFzVl1mv2-RIdmtDskP9be4WyFve-QQDc421oDo_U9CbhDcJEMfti6QylxOFoTiW_JEm1cd9BbIHWAX9ZZ7KONpLEhabsr0gbfkXTPVB9J_GZ7Uls_RIvxcfagTcr4ZHqfZV_fvf1y8WG2_PR-cXG-nJmyzMcZUCbKoqFKUi5ANCCxbSopqqqtZEVrKLEsDFd5ToVQoLBsmeJI84pJamjBz7LnB93B-ain7KLOFU0deUojEYsD0XjY6CHYDsKV9mD134IPKw0hOXaoU6SSybpGVHUhUVQUTZ6bRilRAYf9tDfTtG3dYWOS7QDuSPT4pLdrvfI7zSgt0y8qk8LLSSH471uMo-5sNOgc9Oi36eJSKUWpqPKEvvgHvdveRK0gObB969NgsxfV57IoZMGY2FPzO6j0NNhZ43tsbaofNbw6akjMiD_HFWxj1IvLz__BfjxmiwNrgo8xYHsTHqN6v__XJvV-__W0_6nt2e3gb5quF57_AYCQAjc</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2802052940</pqid></control><display><type>article</type><title>Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><source>Public Library of Science (PLoS)</source><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</creator><creatorcontrib>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</creatorcontrib><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.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1011230</identifier><identifier>PMID: 36940219</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PLoS pathogens, 2023-03, Vol.19 (3), p.e1011230</ispartof><rights>Copyright: © 2023 Pilling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Pilling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Pilling et al 2023 Pilling et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c662t-a01564d087035a5da7efd97599f9790ba6e64c38220558a8e6f183e029170c043</citedby><cites>FETCH-LOGICAL-c662t-a01564d087035a5da7efd97599f9790ba6e64c38220558a8e6f183e029170c043</cites><orcidid>0000-0002-2865-4589</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063166/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063166/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36940219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pilling, Olivia A</creatorcontrib><creatorcontrib>Reis-Cunha, João L</creatorcontrib><creatorcontrib>Grace, Cooper A</creatorcontrib><creatorcontrib>Berry, Alexander S F</creatorcontrib><creatorcontrib>Mitchell, Matthew W</creatorcontrib><creatorcontrib>Yu, Jane A</creatorcontrib><creatorcontrib>Malekshahi, Clara R</creatorcontrib><creatorcontrib>Krespan, Elise</creatorcontrib><creatorcontrib>Go, Christina K</creatorcontrib><creatorcontrib>Lombana, Cláudia</creatorcontrib><creatorcontrib>Song, Yun S</creatorcontrib><creatorcontrib>Amorim, Camila F</creatorcontrib><creatorcontrib>Lago, Alexsandro S</creatorcontrib><creatorcontrib>Carvalho, Lucas P</creatorcontrib><creatorcontrib>Carvalho, Edgar M</creatorcontrib><creatorcontrib>Brisson, Dustin</creatorcontrib><creatorcontrib>Scott, Phillip</creatorcontrib><creatorcontrib>Jeffares, Daniel C</creatorcontrib><creatorcontrib>Beiting, Daniel P</creatorcontrib><title>Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><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.</description><subject>Amplification</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Brazil</subject><subject>Care and treatment</subject><subject>Computer and Information Sciences</subject><subject>Cutaneous leishmaniasis</subject><subject>Design</subject><subject>Diagnosis</subject><subject>Drug resistance</subject><subject>Experimental infection</subject><subject>Failure rates</subject><subject>Gene amplification</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genetics, Population</subject><subject>Genome, Protozoan - genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Health services</subject><subject>Humans</subject><subject>Infections</subject><subject>Leishmania</subject><subject>Leishmania braziliensis</subject><subject>Leishmania braziliensis - genetics</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Medicine, Experimental</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Parasitology - methods</subject><subject>Patients</subject><subject>People and places</subject><subject>Phenotypes</subject><subject>Population genetics</subject><subject>Skin</subject><subject>Skin - parasitology</subject><subject>Tropical diseases</subject><subject>Vector-borne diseases</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVkk-P0zAQxSMEYpeFb4DAEhc4tNhxHDsntFrxp1IFEgtna-JMWhcnDnZaWC58dVyaXW3RXlAOica_eeP3Mln2lNE545K93vht6MHNhwHGOaOM5Zzey06ZEHwmuSzu3_o-yR7FuKG0YJyVD7MTXlYFzVl1mv2-RIdmtDskP9be4WyFve-QQDc421oDo_U9CbhDcJEMfti6QylxOFoTiW_JEm1cd9BbIHWAX9ZZ7KONpLEhabsr0gbfkXTPVB9J_GZ7Uls_RIvxcfagTcr4ZHqfZV_fvf1y8WG2_PR-cXG-nJmyzMcZUCbKoqFKUi5ANCCxbSopqqqtZEVrKLEsDFd5ToVQoLBsmeJI84pJamjBz7LnB93B-ain7KLOFU0deUojEYsD0XjY6CHYDsKV9mD134IPKw0hOXaoU6SSybpGVHUhUVQUTZ6bRilRAYf9tDfTtG3dYWOS7QDuSPT4pLdrvfI7zSgt0y8qk8LLSSH471uMo-5sNOgc9Oi36eJSKUWpqPKEvvgHvdveRK0gObB969NgsxfV57IoZMGY2FPzO6j0NNhZ43tsbaofNbw6akjMiD_HFWxj1IvLz__BfjxmiwNrgo8xYHsTHqN6v__XJvV-__W0_6nt2e3gb5quF57_AYCQAjc</recordid><startdate>20230301</startdate><enddate>20230301</enddate><creator>Pilling, Olivia A</creator><creator>Reis-Cunha, João L</creator><creator>Grace, Cooper A</creator><creator>Berry, Alexander S F</creator><creator>Mitchell, Matthew W</creator><creator>Yu, Jane A</creator><creator>Malekshahi, Clara R</creator><creator>Krespan, Elise</creator><creator>Go, Christina K</creator><creator>Lombana, Cláudia</creator><creator>Song, Yun S</creator><creator>Amorim, Camila F</creator><creator>Lago, Alexsandro S</creator><creator>Carvalho, Lucas P</creator><creator>Carvalho, Edgar M</creator><creator>Brisson, Dustin</creator><creator>Scott, Phillip</creator><creator>Jeffares, Daniel C</creator><creator>Beiting, Daniel P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2865-4589</orcidid></search><sort><creationdate>20230301</creationdate><title>Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c662t-a01564d087035a5da7efd97599f9790ba6e64c38220558a8e6f183e029170c043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Amplification</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Biopsy</topic><topic>Brazil</topic><topic>Care and treatment</topic><topic>Computer and Information Sciences</topic><topic>Cutaneous leishmaniasis</topic><topic>Design</topic><topic>Diagnosis</topic><topic>Drug resistance</topic><topic>Experimental infection</topic><topic>Failure rates</topic><topic>Gene amplification</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Genetics, Population</topic><topic>Genome, Protozoan - genetics</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Health aspects</topic><topic>Health services</topic><topic>Humans</topic><topic>Infections</topic><topic>Leishmania</topic><topic>Leishmania braziliensis</topic><topic>Leishmania braziliensis - genetics</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Medicine, Experimental</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Parasitology - methods</topic><topic>Patients</topic><topic>People and places</topic><topic>Phenotypes</topic><topic>Population genetics</topic><topic>Skin</topic><topic>Skin - parasitology</topic><topic>Tropical diseases</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pilling, Olivia A</creatorcontrib><creatorcontrib>Reis-Cunha, João L</creatorcontrib><creatorcontrib>Grace, Cooper A</creatorcontrib><creatorcontrib>Berry, Alexander S F</creatorcontrib><creatorcontrib>Mitchell, Matthew W</creatorcontrib><creatorcontrib>Yu, Jane A</creatorcontrib><creatorcontrib>Malekshahi, Clara R</creatorcontrib><creatorcontrib>Krespan, Elise</creatorcontrib><creatorcontrib>Go, Christina K</creatorcontrib><creatorcontrib>Lombana, Cláudia</creatorcontrib><creatorcontrib>Song, Yun S</creatorcontrib><creatorcontrib>Amorim, Camila F</creatorcontrib><creatorcontrib>Lago, Alexsandro S</creatorcontrib><creatorcontrib>Carvalho, Lucas P</creatorcontrib><creatorcontrib>Carvalho, Edgar M</creatorcontrib><creatorcontrib>Brisson, Dustin</creatorcontrib><creatorcontrib>Scott, Phillip</creatorcontrib><creatorcontrib>Jeffares, Daniel C</creatorcontrib><creatorcontrib>Beiting, Daniel P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pilling, Olivia A</au><au>Reis-Cunha, João L</au><au>Grace, Cooper A</au><au>Berry, Alexander S F</au><au>Mitchell, Matthew W</au><au>Yu, Jane A</au><au>Malekshahi, Clara R</au><au>Krespan, Elise</au><au>Go, Christina K</au><au>Lombana, Cláudia</au><au>Song, Yun S</au><au>Amorim, Camila F</au><au>Lago, Alexsandro S</au><au>Carvalho, Lucas P</au><au>Carvalho, Edgar M</au><au>Brisson, Dustin</au><au>Scott, Phillip</au><au>Jeffares, Daniel C</au><au>Beiting, Daniel P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2023-03-01</date><risdate>2023</risdate><volume>19</volume><issue>3</issue><spage>e1011230</spage><pages>e1011230-</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36940219</pmid><doi>10.1371/journal.ppat.1011230</doi><tpages>e1011230</tpages><orcidid>https://orcid.org/0000-0002-2865-4589</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1553-7374 |
ispartof | PLoS pathogens, 2023-03, Vol.19 (3), p.e1011230 |
issn | 1553-7374 1553-7366 1553-7374 |
language | eng |
recordid | cdi_plos_journals_2802052940 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
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 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T21%3A09%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Selective%20whole-genome%20amplification%20reveals%20population%20genetics%20of%20Leishmania%20braziliensis%20directly%20from%20patient%20skin%20biopsies&rft.jtitle=PLoS%20pathogens&rft.au=Pilling,%20Olivia%20A&rft.date=2023-03-01&rft.volume=19&rft.issue=3&rft.spage=e1011230&rft.pages=e1011230-&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1011230&rft_dat=%3Cgale_plos_%3EA744741150%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2802052940&rft_id=info:pmid/36940219&rft_galeid=A744741150&rft_doaj_id=oai_doaj_org_article_737717bbee8b47e590ec22cd8859a3a4&rfr_iscdi=true |