Intestinal bacteria hijack an evolutionarily conserved epithelial repair signal
Apoptosis in the gut triggers an expansion in the Enterobacteriaceae family of bacteria, causing both prolonged tissue injury and delayed repair. However, the mechanisms linking the Enterobacteriaceae bloom and subsequent deleterious tissue response are relatively unknown. Here, we establish purines as a major component of the apoptotic secretome that are consumed by bacteria. Explicitly, we…
Apoptosis occurring in the gut triggers an increase in the Enterobacteriaceae family of bacteria, leading to prolonged tissue injury and delayed repair. The connection between the bloom of Enterobacteriaceae and the negative impact on tissue is not entirely clear. This study reveals purines as a significant component of the apoptotic secretome that is consumed by bacteria.
Specifically, hypoxanthine, a critical metabolite, is taken up and metabolized by both harmful and harmless species within the Enterobacteriaceae family. Epithelial cells release hypoxanthine into the extracellular space during the early stages of apoptosis through the upregulation of equilibrative nucleoside transporters 1/2 (ENT1/2).
This discovery not only establishes a link between the host and the microbe but also explains how hypoxanthine aids in the repair of damaged epithelial tissue. Hypoxanthine, a potent promoter of epithelial cell repair across various species, including humans, mice, zebrafish, and fruit flies, stimulates similar ATP production and cellular proliferation in both eukaryotic and microbial recipients.
Consequently, the exclusive consumption of hypoxanthine by the Enterobacteriaceae competes with the host for this essential reparative signal.
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