Biology subjects

Schrimpe-Rutledge, A. C.

Publications and source records attributed to Schrimpe-Rutledge, A. C..

5 recordsLinked to original sources

bioRxiv2026

Rational engineering of facultative anaerobiosis enables commensal survival in the oxygenated gut

Life originated in the absence of oxygen. Despite its substantial energetic advantages, many modern microbes remain obligate anaerobes, confined to anoxic niches such as the mammalian gut. Why these organisms cannot tolerate oxygen has remained unresolved for more than two centuries. Here, using integrated multi-omics analyses, we identify a network of interlocking vulnerabilities in central metabolism, biosynthetic pathways, and redox homeostasis that together impose an aerobic growth barrier in the obligate anaerobic commensal Bacteroides thetaiotaomicron. Rational repair of these vulnerabilities restores metabolic integrity and progressively enhances oxygen tolerance, yielding engineered strains capable of robust growth at 10% O2 and markedly improved resilience in the oxygenated, inflamed gut. These findings define a molecular basis for obligate anaerobiosis and establish a framework for engineering commensal bacteria to function in oxidative environments, expanding their ecological range and therapeutic potential.

microbiology↗

bioRxiv2025

Dehydration promotes intracellular lipid synthesis and accumulation

Lipids can be considered a water reservoir used to offset dehydration stress as their oxidation by the mitochondria generates water. However, whether dehydration and the ensuing hypertonic stress directly regulate lipid synthesis is unknown. We found that hypertonic stress decreases cellular oxygen consumption, increases intracellular lipid synthesis, and favors glutamine oxidation as a carbon precursor for lipid synthesis via remodeling mitochondrial metabolism. These findings provide a mechanism whereby cellular dehydration leads to intracellular lipid accumulation, functionally linking water availability to lipid storage.

physiology↗

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↗

bioRxiv2025

Short-term alterations in dietary amino acids override host genetic susceptibility and reveal mechanisms of Salmonella Typhimurium small intestine colonization

In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S. Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S. Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S. Tm ileal expansion to be microbiota-dependent. Mechanistically, S. Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiotas ability to prevent S. Tm ileal colonization.

microbiology↗

bioRxiv2022

Serine Deamination as a New Acid Resistance Mechanism in Escherichia coli

Escherichia coli associates with humans early in life and can occupy several body niches either as a commensal in the gut and vagina, or as a pathogen in the urinary tract. As such, E. coli has an arsenal of acid response mechanisms that allow it to withstand the different levels of acid stress encountered within and outside the host. Here, we report the discovery of an additional acid response mechanism that involves the deamination of L-serine to pyruvate by the conserved L-serine deaminases SdaA and SdaB. L-serine is the first amino acid to be imported in E. coli during growth in laboratory media, as the culture senesces. However, there remains a lack in knowledge as to why L-serine is preferred and how it is utilized. We show that in acidified media, L-serine is brought into the cell via the SdaC transporter and deletion of both SdaA and SdaB renders E. coli susceptible to acid stress, with a phenotype similar to other acid stress deletion mutants. We also show that the pyruvate produced by L-serine de-amination activates the pyruvate sensor BtsS, which in concert with the non-cognate response regulator YpdB upregulates the putative transporter YhjX, similar to what has been reported for this system during transition of E. coli to stationary phase. Based on these observations, we propose that L-serine deamination constitutes another acid response mechanism in E. coli that may function to protect E. coli as it transitions to stationary phase of growth. IMPORTANCEThe observation that L-serine uptake occurs as an E. coli culture senesces is well-established, yet the benefit E. coli garners from this uptake remains unclear. Here, we report a novel acid resistance mechanism, where L-serine is deaminated to pyruvate and ammonia, promoting acid tolerance in E. coli. This study is important as it provides evidence of the use of L-serine as an acid response strategy, not previously reported for E. coli.

microbiology↗