Enterohemorrhagic Escherichia coli senses low biotin status in the large intestine for colonization and infection.

Bin Yang,Lei Wang,Fang Wang,Lu Feng

doi:10.1038/ncomms7592

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. Here we identify a virulence-regulating pathway in which the biotin protein ligase BirA signals to the global regulator Fur, which in turn activates LEE (locus of enterocyte effacement) genes to promote EHEC adherence in the low-biotin large intestine. LEE genes are repressed in the high-biotin small intestine, thus preventing adherence and ensuring selective colonization of the large intestine. The presence of this pathway in all nine EHEC serotypes tested indicates that it is an important evolutionary strategy for EHEC. The pathway is incomplete in closely related small-intestinal enteropathogenic E. coli due to the lack of the Fur response to BirA. Mice fed with a biotin-rich diet show significantly reduced EHEC adherence, indicating that biotin might be useful to prevent EHEC infection in humans.

Highlights

Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine
The ability to form A/E lesions is conferred by the locus of enterocyte effacement (LEE), which consists of five polycistronic operons (LEE1 to LEE5) that are conserved in all A/E-forming pathogens[3,5]
EHEC has developed strategies for consuming mucus-derived carbohydrates more rapidly than the resident bacteria[31] and for intimately adhering to host epithelial cells via the formation of A/E lesions[5]. The adoption of this BirA-mediated biotin signalling regulatory pathway to control the expression of LEE genes allows EHEC to recognize the large intestine for adhesion

Summary

Introduction

Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. We identify a virulence-regulating pathway in which the biotin protein ligase BirA signals to the global regulator Fur, which in turn activates LEE (locus of enterocyte effacement) genes to promote EHEC adherence in the low-biotin large intestine. LEE genes are repressed in the high-biotin small intestine, preventing adherence and ensuring selective colonization of the large intestine. The presence of this pathway in all nine EHEC serotypes tested indicates that it is an important evolutionary strategy for EHEC. Bile-salt treatment had no effect on LEE gene expression in EHEC19 Whether these factors are linked to the site-specific colonization of EHEC and EPEC needs to be examined further. No involvement of this biotin-dependent regulator in non-biotinrelated processes has been reported

Methods

Results

Conclusion