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bioRxiv · 10.1101/274878

Perforin-2 Permeabilizes the Envelope of Phagocytosed Bacteria

Bai, F.·McCormack, R.·Hower, S.·Plano, G. V.·Lichtenheld, M.·Munson, G. P.
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Abstract

Perforin-2, the product of the MPEG1 gene, limits the spread and dissemination of bacterial pathogens in vivo. It is highly expressed in murine and human phagocytes, and macrophages lacking Perforin-2 are compromised in their ability to kill phagocytosed bacteria. In this study we used Salmonella typhimurium as a model intracellular pathogen to elucidate the mechanism of Perforin-2 s bactericidal activity. In vitro Perforin-2 was found to facilitate the degradation of antigens contained within the envelope of phagocytosed bacteria. In contrast, degradation of a representative surface antigen was found to be independent of Perforin-2. Consistent with our in vitro results a protease sensitive, periplasmic superoxide disumutase (SodCII) contributed to the virulence of S. typhimurium in Perforin-2 knockout but not wild-type mice. In aggregate our studies indicate that Perforin-2 breaches the envelope of phagocytosed bacteria facilitating the delivery of proteases and other antimicrobial effectors to sites within the bacterial envelope.

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Bai, F., McCormack, R., Hower, S., Plano, G. V., Lichtenheld, M., Munson, G. P.. 2018-03-02. Perforin-2 Permeabilizes the Envelope of Phagocytosed Bacteria. https://doi.org/10.1101/274878

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