Abstract
Caseous lymphadenitis (CLA) is a chronic disease that affects sheep and goats worldwide, and its etiological agent is Corynebacterium pseudotuberculosis. Despite the economic losses caused by CLA, there is little information about the molecular mechanisms of bacterial pathogenesis, and current immune prophylaxis against infection has been unable to reduce the incidence of CLA in goats. Recently, 21 different mutant strains of C. pseudotuberculosis were identified by random mutagenesis. In this study, these previously generated mutants were used in mice vaccination trials to develop new immunogens against CLA. Based on this analysis, CZ171053, an iron-acquisition-deficient mutant strain, was selected. After challenge with a virulent strain, 80% of the animals that were immunized with the CZ171053 strain survived. Furthermore, this vaccination elicited both humoral and cellular responses. Intracellular survival of the bacterium was determined using murine J774 cells; in this assay, the CZ171053 had reduced intracellular viability. Because iron acquisition in intracellular bacteria is considered one of their most important virulence factors during infection, these results demonstrate the immunogenic potential of this mutant against CLA.
Highlights
Corynebacterium pseudotuberculosis is a facultative grampositive intracellular pathogen that is the etiological agent of caseous lymphadenitis (CLA) in sheep and goats
Immunization assay, challenge and assessment of protection level Using a transposon-based random mutagenesis system, 34 alkaline phosphatase-positive recombinant strains of C. pseudotuberculosis were obtained; in these strains transposon insertions were identified at 21 different loci
Mice that were inoculated with the CZ171053 recombinant C. pseudotuberculosis strain, which is an ironacquisition-defective mutant, showed the best protection significantly higher levels of C. pseudotuberculosis-specific IgG, IgG1 and IgG2a than the control mice (Figure 3), indicating that the humoral immune response was activated by the immunization
Summary
Corynebacterium pseudotuberculosis is a facultative grampositive intracellular pathogen that is the etiological agent of caseous lymphadenitis (CLA) in sheep and goats. CLA is a chronic debilitating infection, and its main symptoms can be divided into external CLA, which affects superficial lymph nodes, and internal CLA, which leads to the development of abscesses in internal lymph nodes and organs, including the liver, lungs and kidneys [1,2,3] This disease has a worldwide distribution and causes economic losses in several countries, principally to producers in developing countries such as Brazil, where sheep and goat breeding are of increasing economic importance [4,5,6,7,8,9,10]. Driven by the paucity of information on the molecular basis of C. pseudotuberculosis virulence, we identified and characterized bacterial genes based on the cellular localization of their products, focusing mainly on those proteins that are anchored and secreted To identify such genes, we used, for the first time in this species, a reporter transposon-based system named TnFuZ [28]. We studied the cytokine and immunoglobulin production induced by the best vaccine candidates
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