Carbon utilization of Salmonella Typhimurium in different mouse models and on the family level of Enterobacteriaceae

Salmonella Typhimurium (S. Tm) is a common foodborne pathogen and a well-established pathogenic Enterobacterium to study colonization and infection of mammalian hosts. S. Tm invades the gastrointestinal tract and causes inflammation, which drastically changes the gut luminal environment, providing S. Tm with inorganic electron acceptors to bloom and outcompete the resident microbiota (1). However, it is largely unknown which carbon sources S. Tm utilizes at the onset of invasion. For this reason, mutant pools representing the metabolic capacity of S. Tm specifically sugar degradation were constructed, with each mutant labeled with a wild-type isogenic standardized hybrid (WISH) tag (2). The WISH tag is unique for each mutant and can be quantified by qPCR or Illumina sequencing, allowing us to study the fitness of several mutants. To modulate niche competition, the mutant pool will be studied in different mouse models and challenged in the presence of different competitors. Host physiology, e.g., colonization resistance and microbiota composition are known to impact S. Tm colonization (3). In a complementary approach, we looked at the family level of Enterobacteriaceae and identified the core and the accessory genome. Our focus was specifically on carbon utilization, leading to the identification of a core metabolic network centered around simple sugars and mixed acid fermentation. This observation aligns seamlessly with our in vivo data concerning S. Tm. Our investigation promises to uncover crucial insights into the significant metabolic pathways governing the initial growth of S. Tm. Additionally, we aim to identify shared metabolic traits within the family of Enterobacteriaceae that are imperative for invading mammalian hosts. By combining both species and family-level approaches, we aspire to unravel key metabolic characteristics inherent to Enterobacteriaceae.

(1) Rogers, A. W., Tsolis, R. M., & Bäumler, A. J. (2021). Microbiol. Mol. Biol. Rev, 85(1), e00027-19.

(2) Daniel, B. et al, (2024). Nat. Microbiol, accepted.

(3) Herzog, M. K. M., ... & Hardt, W. D. (2023). Gut microbes, 15(1), 2172667.