1887

Abstract

causes chronic lung infections in patients suffering from cystic fibrosis and chronic granulomatous disease. We have previously shown that survives intracellularly in macrophages within a membrane vacuole (BcCV) that delays acidification. Here, we report that after macrophage infection with live there is a ∼6 h delay in the association of NADPH oxidase with BcCVs, while heat-inactivated bacteria are normally trafficked into NADPH oxidase-positive vacuoles. BcCVs in macrophages treated with a functional inhibitor of the cystic fibrosis transmembrane conductance regulator exhibited a further delay in the assembly of the NADPH oxidase complex at the BcCV membrane, but the inhibitor did not affect NADPH oxidase complex assembly onto vacuoles containing heat-inactivated or live . Macrophages produced less superoxide following infection as compared to heat-inactivated and controls. Reduced superoxide production was associated with delayed deposition of cerium perhydroxide precipitates around BcCVs of macrophages infected with live , as visualized by transmission electron microscopy. Together, our results demonstrate that intracellular resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane. This phenomenon may contribute to preventing the efficient clearance of this opportunistic pathogen from the infected airways of susceptible patients.

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2009-04-01
2019-10-18
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