Biology subjects

Fansler, R. T.

Publications and source records attributed to Fansler, R. T..

3 recordsLinked to original sources

bioRxiv2025

An RNA regulates iron homeostasis and host mucus colonization in Bacteroides thetaiotaomicron

Symbiotic bacteria in the human intestinal microbiota provide many pivotal functions to human health and occupy distinct biogeographic niches within the gut. Yet the molecular basis underlying niche-specific colonization remains poorly defined. To address this, we conducted a time-resolved dual RNA-seq experiment to simultaneously monitor the transcriptional co-adaptations of human commensal Bacteroides thetaiotaomicron and human gut epithelial cells in an anaerobe-epithelium co-culture system. Comparative transcriptomic analysis of mucus-associated versus supernatant Bacteroides populations unveiled small RNAs (sRNAs) that are differentially regulated between spatially segregated subpopulations. Among these, we identified IroR as a key sRNA that facilitates B. thetaiotaomicron adaptation to the mucus-rich, iron-limiting niche, partly by modulating expression of bacterial capsule genes. This work provides new insights into the spatiotemporal dynamics of gut colonization and underscores a previously underappreciated role for bacterial sRNAs in shaping mutualistic interactions between the human microbiota and the gut epithelium.

microbiology↗

bioRxiv2025

An Anaerobic Pathogen Rewires Host Metabolism to Fuel Oxidative Growth in the Inflamed Gut

To colonize their host and cause disease, enteric pathogens must deploy their virulence factors to establish distinct nutrient niches. How obligate anaerobic pathogens construct nutrient niches in the densely populated large intestine remains poorly understood. Enterotoxigenic Bacteroides fragilis (ETBF) is considered an obligate anaerobic bacterium and has been implicated in inflammation-associated diseases, including colitis and colorectal cancer. Here we show that ETBF uses its virulence factor, Bacteroides fragilis toxin, to reprogram colonic epithelial cell metabolism to colonize the inflamed gut. Bacteroides fragilis toxin activates colonic epithelial signaling and hijacks the host bile acid recycling pathway, inducing a metabolic shift in the epithelium from oxidative phosphorylation to glycolysis. This shift increases local concentrations of lactate and oxygen, nutrients that support an oxidative metabolism in ETBF. These findings reveal an unexpected strategy by which a pathogenic organism, previously considered to be an obligate anaerobic bacterium, generates and exploits an oxidative niche in the inflamed gut.

microbiology↗

bioRxiv2023

Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients such as iron. Pathogens scavenge iron using siderophores, which is counteracted by the host using lipocalin-2, a protein that sequesters iron-laden siderophores, including enterobactin. Although the host and pathogens compete for iron in the presence of gut commensal bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored. Here, we report that the gut commensal Bacteroides thetaiotaomicron acquires iron in the inflamed gut by utilizing siderophores produced by other bacteria including Salmonella, via a secreted siderophore-binding lipoprotein termed XusB. Notably, XusB-bound siderophores are less accessible to host sequestration by lipocalin-2 but can be "re-acquired" by Salmonella, allowing the pathogen to evade nutritional immunity. As the host and pathogen have been the focus of studies of nutritional immunity, this work adds commensal iron metabolism as a previously unrecognized mechanism modulating the interactions between pathogen and host nutritional immunity.

microbiology↗