Gene-level analysis of core carbohydrate metabolism across the Enterobacteriaceae pan-genome

Enterobacteriaceae is a diverse bacterial family that commonly colonizes the gastrointestinal tracts of humans and animals, influences host health, and also includes members adapted to colonize the phyllosphere as well as insect hosts. We lack systematic knowledge regarding the core metabolic strategy shared among Enterobacteriaceae. To address this gap, we have analyzed the pan-genome of nearly 20,000 genomes, including Citrobacter, Escherichia, Klebsiella, and Salmonella. We found that genes necessary for monosaccharide-fuelled mixed acid fermentation and (micro-)aerobic respiration are part of the Enterobacteriaceae core genome, whereas most genes involved in anaerobic respiration and carbohydrate utilization are associated to the accessory genome. Most Enterobacteriaceae possess genes enabling the utilization of D-glucose, its epimers, D-glucose-containing disaccharides, and chemically modified derivatives of D-glucose - highlighting the evolutionary adaptation of this family to efficiently exploit this simple sugar. Understanding Enterobacteriaceae's core metabolic strategy helps clarify the distinction of niche-defining nutrient sources, which can be genus-, species- or strain-specific. This study highlights the core metabolic strategy of Enterobacteriaceae, supporting the development of targeted interventions in microbiome research and infectious disease control.