Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections

SUMMARY:

Enterococcus faecalis is commonly isolated from a variety of wound types. Despite its prevalence, the pathogenic mechanisms of E. faecalis during wound infection are poorly understood. Using a mouse wound infection model, the authors led by Prof. Kimberly Kline performed in vivo E. faecalis transposon sequencing and RNA sequencing to identify fitness determinants that are crucial for replication and persistence of E. faecalis during wound infection. They found that E. faecalis purine biosynthesis genes are important for bacterial replication during the early stages of wound infection, a time when purine metabolites are consumed by E. faecalis within wounds. They also found that the E. faecalis MptABCD phosphotransferase system (PTS), involved in the import of galactose and mannose, is crucial for E. faecalis persistence within wounds of both healthy and diabetic mice, especially when carbohydrate availability changes throughout the course of infection. During in vitro growth with mannose as the sole carbohydrate source, shikimate and purine biosynthesis genes were downregulated in the OG1RF ∆mptD mutant compared to the isogenic wild-type strain, suggesting a link between mannose transport, shikimate, and purine biosynthesis. Together, their results suggest that dynamic and temporal microenvironment changes at the wound site necessitate concomitant responses by E. faecalis for successful pathogenesis. Moreover, both de novo purine biosynthesis and the MptABCD PTS system also contribute to E. faecalis fitness during catheter-associated urinary tract infection, suggesting that these pathways may be central and niche-independent virulence factors of E. faecalis and raising the possibility of lowering exogenous purine availability and/or targeting galactose/mannose PTS to control wound infections.

Link to full article: https://journals.asm.org/doi/full/10.1128/mbio.02384-23

Why is this important?

Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, using a mouse wound infection, the authors identified two metabolic pathways that are essential for acute replication and persistence of E. faecalis during wound infection. The essentiality of these two processes is due to the consumption of purine metabolites by E. faecalis during acute replication and the change in carbohydrate availability during wound infection. Overall, their findings reveal the importance of the wound microenvironment in the pathogenesis of E. faecalis and how these metabolic pathways can be targeted for better control of wound infections.

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