Chronic wound infections

Gelatinase regulates the egress of intracellular replicating populations during Enterococcus faecalis infection

SUMMARY

Enterococcus faecalis is a common opportunistic pathogen, frequently isolated from chronic wounds, yet the mechanisms underlying its virulence and persistence in this niche remain incompletely understood. The authors previously showed that a subpopulation of E. faecalis can survive intracellularly for several days during murine wound infection and can replicate within macrophages, revealing an unexpected intracellular phase for this traditionally extracellular bacterium. Here, they identify the secreted metalloprotease gelatinase (GelE) and its regulator, the Fsr quorum sensing system, as key modulators of E. faecalis intracellular survival and replication. Mechanistically, Fsr quorum sensing is induced during intracellular replication, promoting GelE-dependent host cell lysis and bacterial egress. In the absence of active GelE, E. faecalis accumulates as large intracellular clusters, a phenotype observed consistently across GelE-deficient wound isolates. In a mouse wound model, GelE-deficient E. faecalis similarly exhibited higher intracellular numbers within wound infection-associated host cells. Together, this study uncovers GelE as a central effector that orchestrates the transition between intracellular and extracellular lifestyles of E. faecalis, providing a possible explanation for its persistence in chronic wound infection.

Full article: https://doi.org/10.1371/journal.ppat.1013738

WHY IS THIS IMPORTANT?

Chronic wound infections are often difficult to treat, partly due to bacteria like Enterococcus faecalis. This study shows that this bacterium can live inside human cells, where it is protected from immune defenses.

The authors of this work discovered that a communication system called quorum sensing activates production of an enzyme (GelE) that allows bacteria to break out of host cells. Without this enzyme, bacteria accumulate inside cells and remain hidden.

This matters because intracellular bacteria may act as reservoirs, causing persistent or recurring infections. Understanding this mechanism could help design treatments that better eliminate bacteria hiding inside cells, which is key to managing chronic infections more effectively.

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