SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice.
Leishmania species are sand fly-transmitted protozoan parasites that cause leishmaniasis, neglected tropical diseases that affect millions of people. Leishmania amastigotes must overcome a variety of host defenses, including reactive oxygen species (ROS) produced by the NADPH oxidase. Leishmania spe...
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ftdoajarticles:oai:doaj.org/article:ac0e9b0003914442986e96da9f3d93e1 2023-05-15T15:09:45+02:00 SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. Bennett J Davenport Casey G Martin Stephen M Beverley David J Orlicky Andres Vazquez-Torres Thomas E Morrison 2018-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006921 https://doaj.org/article/ac0e9b0003914442986e96da9f3d93e1 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6224164?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006921 https://doaj.org/article/ac0e9b0003914442986e96da9f3d93e1 PLoS Neglected Tropical Diseases, Vol 12, Iss 10, p e0006921 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006921 2022-12-31T01:48:39Z Leishmania species are sand fly-transmitted protozoan parasites that cause leishmaniasis, neglected tropical diseases that affect millions of people. Leishmania amastigotes must overcome a variety of host defenses, including reactive oxygen species (ROS) produced by the NADPH oxidase. Leishmania species encode three superoxide dismutases (SODs): the mitochondrial SODA and two glycosomal SODs (SODB1 and SODB2). SODs are metalloenzymes that function in antioxidant defense by converting superoxide to oxygen and hydrogen peroxide. Here, we investigated a role for SODB1 in Leishmania infection of macrophages and virulence in mice. We found that a single allele deletion of SODB1 (SODB1/Δsodb1) had minimal effects on the replication of axenically-grown L. major promastigotes or differentiation to infective metacyclic promastigotes. Disruption of a single SODB1 allele also did not affect L. donovani differentiation to amastigotes induced axenically, or the replication of axenically-grown L. donovani promastigotes and amastigotes. In contrast, the persistence of SODB1/Δsodb1 L. major in WT macrophages was impaired, and the development of cutaneous lesions in SODB1/Δsodb1 L. major-infected C57BL/6 and BALB/c mice was strongly reduced. The reduced disease severity in mice was associated with reduced burdens of SODB1/Δsodb1 L. major parasites in the foot at late, but not early times post-inoculation, as well as an impaired capacity to disseminate from the site of inoculation. Collectively, these data suggest that SODB1 is critical for L. major persistence in macrophages and virulence in mice. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 10 e0006921 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Bennett J Davenport Casey G Martin Stephen M Beverley David J Orlicky Andres Vazquez-Torres Thomas E Morrison SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leishmania species are sand fly-transmitted protozoan parasites that cause leishmaniasis, neglected tropical diseases that affect millions of people. Leishmania amastigotes must overcome a variety of host defenses, including reactive oxygen species (ROS) produced by the NADPH oxidase. Leishmania species encode three superoxide dismutases (SODs): the mitochondrial SODA and two glycosomal SODs (SODB1 and SODB2). SODs are metalloenzymes that function in antioxidant defense by converting superoxide to oxygen and hydrogen peroxide. Here, we investigated a role for SODB1 in Leishmania infection of macrophages and virulence in mice. We found that a single allele deletion of SODB1 (SODB1/Δsodb1) had minimal effects on the replication of axenically-grown L. major promastigotes or differentiation to infective metacyclic promastigotes. Disruption of a single SODB1 allele also did not affect L. donovani differentiation to amastigotes induced axenically, or the replication of axenically-grown L. donovani promastigotes and amastigotes. In contrast, the persistence of SODB1/Δsodb1 L. major in WT macrophages was impaired, and the development of cutaneous lesions in SODB1/Δsodb1 L. major-infected C57BL/6 and BALB/c mice was strongly reduced. The reduced disease severity in mice was associated with reduced burdens of SODB1/Δsodb1 L. major parasites in the foot at late, but not early times post-inoculation, as well as an impaired capacity to disseminate from the site of inoculation. Collectively, these data suggest that SODB1 is critical for L. major persistence in macrophages and virulence in mice. |
format |
Article in Journal/Newspaper |
author |
Bennett J Davenport Casey G Martin Stephen M Beverley David J Orlicky Andres Vazquez-Torres Thomas E Morrison |
author_facet |
Bennett J Davenport Casey G Martin Stephen M Beverley David J Orlicky Andres Vazquez-Torres Thomas E Morrison |
author_sort |
Bennett J Davenport |
title |
SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. |
title_short |
SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. |
title_full |
SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. |
title_fullStr |
SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. |
title_full_unstemmed |
SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice. |
title_sort |
sodb1 is essential for leishmania major infection of macrophages and pathogenesis in mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006921 https://doaj.org/article/ac0e9b0003914442986e96da9f3d93e1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 10, p e0006921 (2018) |
op_relation |
http://europepmc.org/articles/PMC6224164?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006921 https://doaj.org/article/ac0e9b0003914442986e96da9f3d93e1 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006921 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
10 |
container_start_page |
e0006921 |
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