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- Title
SODB1 is essential for Leishmania major infection of Macrophages and Pathogenesis in Mice.
- Authors
Davenport, Bennett J.; Martin, Casey G.; Beverley, Stephen M.; Orlicky, David J.; Vazquez-Torres, Andres; Morrison, Thomas E.
- 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/⊗sodb1) 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/⊗sodb1 L. major in WT macrophages was impaired, and the development of cutaneous lesions in SODB1/⊗sodb1 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/⊗sodb1 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.
- Subjects
REACTIVE oxygen species; SUPEROXIDE dismutase genetics; MACROPHAGE activation; LABORATORY rats; ANIMAL vaccination
- Publication
PLoS Neglected Tropical Diseases, 2018, Vol 12, Issue 10, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0006921