Abstract
SummaryHaemolytic uraemic syndrome caused by Shiga toxin-producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx-related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx-related events and enhance Stx absorption during STEC infection.
Highlights
Shiga toxin-producing E. coli (STEC) are the fourth most common bacterial foodborne pathogen and responsible for around 1200 illnesses per year in the UK (Money et al, 2010)
Our study suggests that the MA environment in the human colon may modulate Shiga toxins (Stxs)-related events and enhance Stx absorption during STEC infection
While all transcytosis studies on polarized Gb3-negative human T84 colon carcinoma cells have been performed with purified Stx1, we have studied Stx production, release and translocation during infection with Stx2-producing STEC O157:H7 and O104:H4 bacterial strains
Summary
Shiga toxin-producing E. coli (STEC) are the fourth most common bacterial foodborne pathogen and responsible for around 1200 illnesses per year in the UK (Money et al, 2010). HUS is the leading cause of acute kidney failure in children in the western world (Tarr et al, 2005). After ingestion via contaminated food or water, STEC adhere to human intestinal epithelium and inject bacterial effector proteins into the host cell through a type III secretion system (T3SS). These effector proteins interfere with host cell signalling and function (e.g. tight junction integrity and alteration of ion channels) which leads to loss of absorptive function and diarrhoea (Viswanathan et al, 2009; Wong et al, 2011).
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