A conserved peptidase governs glucose homeostasis in Bacteroides
Year: 2026
Type: preprint
Abstract: Glucose homeostasis is governed by peptidases across the kingdom of life. Host overconsumption of glucose transforms gut microbial compositions and activities. Here, we identify an IDE-like M16 peptidase in human gut commensal Bacteroides that controls glucose-dependent inhibition of the transcriptional regulator, Cur, which is important for intestinal colonization and host-microbial interactions. This regulatory paradigm is independent of fructose, establishing a specific pathway whereby glucose signaling hinders commensal fitness in the host. We determined that this peptidase cleaves targets of other M16-family peptidases, including insulin, to control carbon metabolism through the oxidative pentose phosphate pathway (OPPP). Furthermore, we show that peptidase activity governs the abundance of glycolytic enzymes to alter Cur activity. These findings establish that the activity of an M16 peptidase mediates changes to global transcription in Bacteroides species when glucose is abundant in the host diet.
Institutions: Pennsylvania State University, Yale University
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Elucidating the consequences of dietary sugar consumption on the gut microbiota, G4122164632, G5933690935, G8008075946, How Bacteroides species coordinate glycogen metabolism and global gene expression to colonize the mammalian intestine, Control of gut colonization by the prominent gut bacterium Bacteroides thetaiotaomicron, Harnessing the gut microbiome to detect and quantify glycans
OpenAlex ID: W7153533833