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Regulation of virulence by butyrate sensing in enterohaemorrhagic Escherichia coli

¹ Division of Applied Microbiology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
² Department of Genetic Resources Technology, Faculty of Agriculture, Kyusyu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan
³ Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kiyotake, Miyazaki 889-1692, Japan

Correspondence
Toru Tobe
torutobe{at}bact.med.osaka-u.ac.jp

Enterohaemorrhagic Escherichia coli (EHEC) colonizes and proliferates at the mucosal surface, inducing severe diarrhoea. Short-chain fatty acids (SCFAs) are abundant in the intestine owing to the metabolic activity of microflora, and are important for colonic health. We found that, although a high concentration of SCFAs inhibited the growth of EHEC, at low concentrations, the SCFAs markedly enhanced the expression of the virulence genes required for cell adherence and the induction of attaching and effacing (A/E) lesions. Of the SCFAs tested, butyrate markedly enhanced the expression of these virulence-associated genes, even at the low concentration of 1.25 mM, but acetate and propionate showed only a small effect at concentrations higher than 40 mM. Butyrate enhanced the promoter activity of the LEE1 operon, which encodes a global regulator of the LEE genes, Ler. This enhancement was dependent on a regulator, PchA. Butyrate sensing was completely abrogated by the deletion of lrp, the gene for the leucine-responsive regulatory protein, Lrp. Expression of a constitutively active mutant of Lrp enhanced the expression of the LEE genes in the absence of butyrate, and a response-defective Lrp derivative reduced the response to butyrate. Thus, upon entering the distal ileum, EHEC may respond to the higher butyrate level via Lrp by increasing its virulence expression, leading to efficient colonization of the target niche.

The GEO accession number for the microarray data associated with this paper is GSE12903.

Four supplementary figures are available with the online version of this paper.