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PLoS Negl Trop Dis. 2018 Oct 29;12(10):e0006921. doi: 10.1371/journal.pntd.0006921. eCollection 2018 Oct.

SODB1 is essential for Leishmania major infection of macrophages and pathogenesis in mice.

Author information

1
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
2
Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
3
Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

Abstract

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.

PMID:
30372439
PMCID:
PMC6224164
DOI:
10.1371/journal.pntd.0006921
[Indexed for MEDLINE]
Free PMC Article

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