GSH-MODIFIED VIRULENCE IN ENTEROBACTERIACEAE

Abstract

Reduced glutathione (GSH) is a low molecular weight thiol found in eukaryotic cells that maintains intracellular redox balance. We discovered that exogenous GSH incubated with various species in the Enterobacteriaceae family can cause the rapid killing of 5’fluorodeoxyuridine (FUDR)-treated Caenorhabditis elegans.

We show that GSH is catabolised to H₂S by bacteria such as Escherichia coli using a tryptophanase known as TnaA. In a colonic epithelial cell line, H₂S reduced cell viability by inhibiting ATP production, exacerbated by FUDR treatment.

In the colon, high GSH levels could lead to H₂S being produced by enteric bacteria. GSH and H₂S could reduce intramolecular disulfide bonds in mucin glycoproteins increasing bacterial adhesion and penetration of the mucus layer and cause inflammation or mucositis. Strategies to manage the availability of GSH to Enterobacteriaceae species in the gut can guide better management of side effects for cancer patients treated with FUDR analogues such as 5-FU.