LeuO enhances butyrate‐induced virulence expression through a positive regulatory loop in enterohaemorrhagic Escherichia coli

Abstract

SummaryEnterohaemorrhagic Escherichia coli (EHEC) causes bloody diarrhoea and other severe symptoms such as haemorrhagic uraemic syndrome. The expression of virulence genes on the locus for enterocyte effacement (LEE) and associated genes is regulated by a variety of factors, including transcriptional regulators and environmental signals. Butyrate, one of the major short-chain fatty acids present in the intestine, enhances expression of LEE genes and flagella biosynthesis genes in EHEC O157:H7, resulting in increased bacterial adherence and motility. Here, we show that expression of the leuO gene, which encodes a LysR-type transcriptional regulator, is enhanced by butyrate via Lrp, which is also necessary for butyrateinduced responses of LEE genes. LeuO expression induces prolonged activation of the promoter of LEE1 operon, including the ler gene, as well as virulence mechanisms such as microcolony formation. Activation of the LEE1 promoter by LeuO depends on another regulator, called Pch. The response of the leuO promoter to butyrate requires two virulence regulators, Pch and Ler, in addition to Lrp. Pch, Ler and Lrp bind the upstream region of the leuO promoter. Thus, leuO is involved in butyrate-enhanced expression of LEE genes through a positive feedback mechanism, but its expression and action on the LEE1 promoter are dependent on the virulence regulators Pch and Ler.

Sodium Butyrate Attenuates Diarrhea in Weaned Piglets and Promotes Tight Junction Protein Expression in Colon in a GPR109A-Dependent Manner

“…Our study did not reveal an obvious change in average daily feed intake, average daily gain, and the feed/gain ratio between the sodium butyrate and control groups, but sodium butyrate exerted a significant effect on ameliorating diarrhea. Sodium butyrate has been shown to relieve diarrhea caused by weaning stress or enterohemorrhagic Escherichia coli in piglets [19][20][21]. Moreover, butyrate therapy is beneficial in patients with congenital chloride diarrhea [22,23], consistent with our results.…”

Interactions between the microbiota and pathogenic bacteria in the gut

“…However, the detailed mechanism of this regulation is yet to be unravelled. In EHEC, exposure to the levels of butyrate found in the colon increases the expression of the EHEC T3SS through post-transcriptional activation of the transcriptional regulator Lrp 42 . Exposure to the concentrations of acetate and propionate that are found in the small intestine does not significantly affect the virulence of EHEC.…”

Ribavirin suppresses bacterial virulence by targeting LysR-type transcriptional regulators

“…LTTRs namely QseA, LeuO and LrhA regulates the LEE genes and the flagellar regulon, and is involved in the microcolony formation and adherence to the epithelial cells20212223. To determine if ribavirin could inhibit LEE genes expression, expression of the target genes ler , a master regulator of LEE and escU in the in vitro cultures of EPEC was quantified by qPCR.…”

“…LTTR family proteins, such as QseA21, LeuO23 and LrhA22 regulate the locus for enterocyte effacement (LEE), which is critical for intestinal colonization and pathogenesis of EPEC and EHEC. Although we failed to identify the LTTR protein which was inhibited by ribavirin, we found that the drug inhibits the expression of LEE genes and colonization of mouse small intestine by EPEC.…”