Work

Yersiniabactin-producing adherent-invasive Escherichia coli exploit host glycolysis to drive macrophage HIF-1α stabilization

Year: 2026

Type: article

Abstract: The siderophore yersiniabactin (Ybt) produced by a subset of intestinal adherent-invasive Escherichia coli (AIEC) drive intestinal fibrosis in murine model of Crohn’s disease (CD). This is linked to the Ybt-induced disruption of host metal homeostasis and activation of the hypoxia-inducible factor 1–alpha (HIF-1α) in macrophages. Elevated glycolytic activity has been documented in both intestinal tissues and macrophages from patients with CD, indicating that metabolic reprogramming is a characteristic feature of the disease. Here, we show that HIF-1α stabilization by Ybt + AIEC requires active host glycolysis. This effect is independent of Hif1a transcription and lipopolysaccharide stimulation and is not solely explained by intracellular bacterial load but instead relies on host metabolic activity. Mechanistically, Ybt + AIEC activated the Akt-mTOR pathway to support HIF-1α translation. Inhibition of glycolysis suppressed this signaling axis, reducing HIF-1α translation and nuclear localization. Given the association between Ybt + AIEC and fibrosis in CD, these findings suggest that targeting host glycolysis may limit AIEC-driven macrophage HIF-1α activation and fibrotic progression in CD patients.

Source: Science Advances