1887

Abstract

Periplasmic copper- and zinc-cofactored superoxide dismutases ([Cu,Zn]-SODs, SodC) of several Gram-negative pathogens can protect against superoxide-radical-mediated host defences, and thus contribute to virulence. This role has been previously defined for one [Cu,Zn]-SOD in various serovars. Following the recent discovery of a second periplasmic [Cu,Zn]-SOD in , the effect of knockout mutations in one or both of the original and the new on the virulence of the porcine pathogen is investigated here. In comparison to wild-type, while mutants – whether single or double – showed no impairment in growth, they all showed equally enhanced sensitivity to superoxide and a dramatically increased sensitivity to the combination of superoxide and nitric oxide . This observation had its correlate in experimental infection both and Mutation of significantly impaired survival of in interferon γ-stimulated murine macrophages compared to wild-type organisms, and all mutants persisted in significantly lower numbers than wild-type in BALB/c ( ) and C3H/HeN ( ) mice after experimental infection, but in no experimental system were double mutants more attenuated than either single mutant. These data suggest that both [Cu,Zn]-SODs are needed to protect bacterial periplasmic or membrane components. While SodC plays a role in virulence, the data presented here suggest that this is through overcoming a threshold effect, probably achieved by acquisition of on a bacteriophage. Loss of either gene confers maximum vulnerability to superoxide on .

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2002-03-01
2021-10-24
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