Enterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization

Bin Liu, Lingyan Jiang, Yutao Liu, Hongmin Sun, Jun Yan, Chenbo Kang and Bin Yang ()
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Bin Liu: Nankai University, TEDA
Lingyan Jiang: Nankai University, TEDA
Yutao Liu: Nankai University, TEDA
Hongmin Sun: Nankai University, TEDA
Jun Yan: Nankai University, TEDA
Chenbo Kang: Nankai University, TEDA
Bin Yang: Nankai University, TEDA

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract The mammalian gastrointestinal tract is a complex environment that hosts a diverse microbial community. To establish infection, bacterial pathogens must be able to compete with the indigenous microbiota for nutrients, as well as sense the host environment and modulate the expression of genes essential for colonization and virulence. Here, we found that enterohemorrhagic Escherichia coli (EHEC) O157:H7 imports host- and microbiota-derived L-malate using the DcuABC transporters and converts these substrates into fumarate to fuel anaerobic fumarate respiration during infection, thereby promoting its colonization of the host intestine. Moreover, L-malate is important not only for nutrient metabolism but also as a signaling molecule that activates virulence gene expression in EHEC O157:H7. The complete virulence-regulating pathway was elucidated; the DcuS/DcuR two-component system senses high L-malate levels and transduces the signal to the master virulence regulator Ler, which in turn activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence to epithelial cells of the large intestine. Disruption of this virulence-regulating pathway by deleting either dcuS or dcuR significantly reduced colonization by EHEC O157:H7 in the infant rabbit intestinal tract; therefore, targeting these genes and altering physiological aspects of the intestinal environment may offer alternatives for EHEC infection treatment.

Date: 2023
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DOI: 10.1038/s41467-023-43149-7

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