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The role of anthrolysin O in gut epithelial barrier disruption during Bacillus anthracis infection.

Abstract：

:Gastrointestinal (GI) anthrax, caused by the bacterial infection of Bacillus anthracis, posts a significant bioterrorism threat by its relatively high mortality rate in humans. Different from inhalational anthrax by the route of infection, accumulating evidence indicates the bypass of vegetative bacteria across GI epithelium is required to initiate GI anthrax. Previously, we reported that purified anthrolysin O (ALO), instead of tripartite anthrax edema and lethal toxins, is capable of disrupting gut epithelial tight junctions and barrier function in cultured cells. Here, we show that ALO can disrupt intestinal tissue barrier function in an ex vivo mouse model. To explore the effects of ALO in a cell culture model of B. anthracis infection, we showed that anthrax bacteria can effectively reduce the monolayer integrity of human Caco-2 brush-border expressor (C2BBE) cells based on the reduced transepithelial resistance and the increased leakage of fluorescent dye. This disruption is likely caused by tight junction dysfunction observed by the reorganization of the tight junction protein occludin. Consequently, we observe significant passage of vegetative anthrax bacteria across C2BBE cells. This barrier disruption and bacterial crossover requires ALO since ALO-deficient B. anthracis strains fail to induce monolayer dysfunction and allow the passage of anthrax bacteria. Together these findings point to a pivotal role for ALO within the establishment of GI anthrax infection and the initial bypass of the epithelial barrier.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Bishop BL,Lodolce JP,Kolodziej LE,Boone DL,Tang WJ

doi

10.1016/j.bbrc.2010.02.091

subject

Has Abstract

pub_date

2010-04-02 00:00:00

pages

254-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)00311-6

journal_volume

394

pub_type

杂志文章

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