A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania.
Infection with Leishmania results in a broad spectrum of pathologies where L. infantum and L. donovani cause fatal visceral leishmaniasis and L. major causes destructive cutaneous lesions. The identification and characterization of Leishmania virulence genes may define the genetic basis for these di...
Published in: | PLoS Neglected Tropical Diseases |
---|---|
Main Authors: | , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2008
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0000248 https://doaj.org/article/f4b3ff48ff054fc0a5726b51f8392f56 |
id |
ftdoajarticles:oai:doaj.org/article:f4b3ff48ff054fc0a5726b51f8392f56 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:f4b3ff48ff054fc0a5726b51f8392f56 2023-05-15T15:11:31+02:00 A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. Wen-Wei Zhang Christopher S Peacock Greg Matlashewski 2008-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000248 https://doaj.org/article/f4b3ff48ff054fc0a5726b51f8392f56 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2398785?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000248 https://doaj.org/article/f4b3ff48ff054fc0a5726b51f8392f56 PLoS Neglected Tropical Diseases, Vol 2, Iss 6, p e248 (2008) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2008 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000248 2022-12-30T21:57:31Z Infection with Leishmania results in a broad spectrum of pathologies where L. infantum and L. donovani cause fatal visceral leishmaniasis and L. major causes destructive cutaneous lesions. The identification and characterization of Leishmania virulence genes may define the genetic basis for these different pathologies.Comparison of the recently completed L. major and L. infantum genomes revealed a relatively small number of genes that are absent or present as pseudogenes in L. major and potentially encode proteins in L. infantum. To investigate the potential role of genetic differences between species in visceral infection, seven genes initially classified as absent in L. major but present in L. infantum were cloned from the closely related L. donovani genome and introduced into L. major. The transgenic L. major expressing the L. donovani genes were then introduced into BALB/c mice to select for parasites with increased virulence in the spleen to determine whether any of the L. donovani genes increased visceral infection levels. During the course of these experiments, one of the selected genes (LinJ32_V3.1040 (Li1040)) was reclassified as also present in the L. major genome. Interestingly, only the Li1040 gene significantly increased visceral infection in the L. major transfectants. The Li1040 gene encodes a protein containing a putative component of an endosomal protein sorting complex involved with protein transport.These observations demonstrate that the levels of expression and sequence variations in genes ubiquitously shared between Leishmania species have the potential to significantly influence virulence and tissue tropism. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 2 6 e248 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Wen-Wei Zhang Christopher S Peacock Greg Matlashewski A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Infection with Leishmania results in a broad spectrum of pathologies where L. infantum and L. donovani cause fatal visceral leishmaniasis and L. major causes destructive cutaneous lesions. The identification and characterization of Leishmania virulence genes may define the genetic basis for these different pathologies.Comparison of the recently completed L. major and L. infantum genomes revealed a relatively small number of genes that are absent or present as pseudogenes in L. major and potentially encode proteins in L. infantum. To investigate the potential role of genetic differences between species in visceral infection, seven genes initially classified as absent in L. major but present in L. infantum were cloned from the closely related L. donovani genome and introduced into L. major. The transgenic L. major expressing the L. donovani genes were then introduced into BALB/c mice to select for parasites with increased virulence in the spleen to determine whether any of the L. donovani genes increased visceral infection levels. During the course of these experiments, one of the selected genes (LinJ32_V3.1040 (Li1040)) was reclassified as also present in the L. major genome. Interestingly, only the Li1040 gene significantly increased visceral infection in the L. major transfectants. The Li1040 gene encodes a protein containing a putative component of an endosomal protein sorting complex involved with protein transport.These observations demonstrate that the levels of expression and sequence variations in genes ubiquitously shared between Leishmania species have the potential to significantly influence virulence and tissue tropism. |
format |
Article in Journal/Newspaper |
author |
Wen-Wei Zhang Christopher S Peacock Greg Matlashewski |
author_facet |
Wen-Wei Zhang Christopher S Peacock Greg Matlashewski |
author_sort |
Wen-Wei Zhang |
title |
A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. |
title_short |
A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. |
title_full |
A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. |
title_fullStr |
A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. |
title_full_unstemmed |
A genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania. |
title_sort |
genomic-based approach combining in vivo selection in mice to identify a novel virulence gene in leishmania. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2008 |
url |
https://doi.org/10.1371/journal.pntd.0000248 https://doaj.org/article/f4b3ff48ff054fc0a5726b51f8392f56 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 2, Iss 6, p e248 (2008) |
op_relation |
http://europepmc.org/articles/PMC2398785?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000248 https://doaj.org/article/f4b3ff48ff054fc0a5726b51f8392f56 |
op_doi |
https://doi.org/10.1371/journal.pntd.0000248 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
2 |
container_issue |
6 |
container_start_page |
e248 |
_version_ |
1766342355900694528 |