1887

Abstract

The gene designated BAB1_0591 in the 2308 genome sequence encodes the manganese-cofactored superoxide dismutase SodA. An isogenic mutant derived from 2308, designated JB12, displays a small colony phenotype, increased sensitivity to endogenous superoxide generators, hydrogen peroxide and exposure to acidic pH, and a lag in growth when cultured in rich and minimal media that can be rescued by the addition of all 20 amino acids to the growth medium. JB12 exhibits significant attenuation in both cultured murine macrophages and experimentally infected mice, but this attenuation is limited to the early stages of infection. Addition of the NADPH oxidase inhibitor apocynin to infected macrophages does not alleviate the attenuation exhibited by JB12, suggesting that the basis for the attenuation of the mutant is not an increased sensitivity to exogenous superoxide generated through the oxidative burst of host phagocytes. It is possible, however, that the increased sensitivity of the mutant to acid makes it less resistant than the parental strain to killing by the low pH encountered during the early stages of the development of the brucella-containing vacuoles in macrophages. These experimental findings support the proposed role for SodA as a major cytoplasmic antioxidant in brucella. Although this enzyme provides a clear benefit to 2308 during the early stages of infection in macrophages and mice, SodA appears to be dispensable once the brucellae have established an infection.

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2012-07-01
2019-12-08
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