Abstract
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 are human pathogens responsible for bloody diarrhea and renal failures. EHEC employ a type 3 secretion system to attach directly to the human colonic epithelium. This structure is encoded by the locus of enterocyte effacement (LEE) whose expression is regulated in response to specific nutrients. In this study, we show that the mucin-derived sugars N-acetylglucosamine (NAG) and N-acetylneuraminic acid (NANA) inhibit EHEC adhesion to epithelial cells through down-regulation of LEE expression. The effect of NAG and NANA is dependent on NagC, a transcriptional repressor of the NAG catabolism in E. coli. We show that NagC is an activator of the LEE1 operon and a critical regulator for the colonization of mice intestine by EHEC. Finally, we demonstrate that NAG and NANA as well as the metabolic activity of Bacteroides thetaiotaomicron affect the in vivo fitness of EHEC in a NagC-dependent manner. This study highlights the role of NagC in coordinating metabolism and LEE expression in EHEC and in promoting EHEC colonization in vivo.
Highlights
Escherichia coli O157:H7 are human foodborne pathogens responsible for outbreaks mostly in developed countries
The effect of N-acetylneuraminic acid (NANA) and NAG on Escherichia coli (EHEC) adhesion was examined by measuring the ability of the EHEC O157:H7 EDL933 strain to adhere to cultured epithelial cells in the presence or absence of NANA or NAG
The adhesion of EHEC O157:H7 to HeLa cells is mainly driven by the production of a T3SS, as previously demonstrated (Branchu et al, 2014) and as verified using the escN strain which is defective in the production of the T3SS (Figure EV1)
Summary
Escherichia coli O157:H7 are human foodborne pathogens responsible for outbreaks mostly in developed countries. Infections by EHEC occur following ingestion of contaminated food and provoke symptoms ranging from watery or bloody diarrhea to hemolytic and uremic syndrome (HUS). A range of virulence factors are involved in EHEC O157:H7 pathogenicity including the Shiga-toxin which is associated with development of HUS, and the T3SS which enables the pathogen to attach to the intestinal epithelium and cause diarrhea (Kaper et al, 2004). T3SS-encoding genes are gathered into the locus of enterocyte effacement (LEE) that is composed of five operons (LEE1 to LEE5) which encode for structural proteins, regulators, chaperones and effectors that are secreted into the host cells (Kaper et al, 2004). The first gene of the LEE, ler, encodes an activator that regulates the five major LEE operons.
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