Transcriptomic and Functional Analysis of NaCl-Induced Stress in <i>Enterococcus faecalis</i>

<div><p>The robust physiology of <i>Enterococcus faecalis</i> facilitates tolerance to various stresses. We here report the transcriptional response of <i>E. faecalis</i> V583 to growth in the presence of 6.5% NaCl. Among the early responses observed was an immediate down-regulation of <i>mscL</i>, accompanied by an up-regulation of genes predicted to be involved in uptake of extracellular potassium and glycine betaine. The high NaCl concentration also induced expression of chaperons and cell envelope related traits, such as the enterococcal polysaccharide antigen (<i>epa</i>) locus. Functional genetic analysis revealed reduced salt stress resistance in both <i>epaB</i> and <i>epaE</i> mutants. The reduced salt resistance phenotype associated with the <i>epaB</i> mutant was restored by complementation, hence demonstrating a role of Epa in the physiological robustness of <i>E. faecalis</i>. Furthermore, we demonstrate that Epa confers increased resistance towards multiple cell envelope stress-inducing factors. Accordingly, these findings delineate a potential link between the robust nature of <i>E. faecalis</i> and its ability to perform as a human pathogen, and provide a new perspective on the mechanisms by which Epa contributes to virulence. Notably, the high NaCl concentration also resulted in strict repression of the <i>gelE-sprE</i> operon and impaired gelatinase activity. We demonstrate that NaCl antagonize the GBAP-pheromone dependent induction in a concentration dependent manner.</p>