The NagY antiterminator in <i>Enterococcus faecalis:</i> a novel regulatory mechanism and its impact on cell metabolism

The <i>Enterococcus</i> genus is the most controversial group of lactic acid bacteria. While some strains are used as probiotics, other species, including <i>Enterococcus faecalis</i>, are responsible for health-related pathologies. Under conditions of infection, the N-acetylglucosamine metabolism of <i>E. faecalis</i> undergoes significant changes in expression, even more important than those of virulence factors. This metabolism is mediated by the <i>nagY-nagE</i> operon, which is regulated by the transcriptional antiterminator NagY. In this report, we focus on the regulatory mechanism of NagY and its impact on bacterial metabolism. We showed that NagY requires the interaction with the RNase III to achieve optimal induction of its own expression by cleaving the 5' untranslated region of the <i>nagY</i> mRNA. The NagY regulon was identified and the central role of the antiterminator in the <i>E. faecalis</i> metabolism was demonstrated, highlighting its importance in the opportunistic nature of the bacterium. This study provides a valuable advance in the understanding of regulation and the importance of post-transcriptional actors in <i>E. faecalis</i> adaptation.IMPORTANCEAs a commensal<i>, Enterococcus faecalis</i> colonizes the gastrointestinal tract of 31 to 80% of the intestinal microbiota in adults and is considered ubiquitous, due to its strong environmental stress resistance capabilities. However, in immunocompromised patients, the poorly understood transition from commensal to opportunistic pathogen occurs, and many studies suggest that the metabolism plays a central role in this process. In this study, we focus on the regulator NagY, which is involved in the metabolism of N-acetylglucosamine, an important carbon source for bacterial pathogens in the human host. We characterized a novel regulatory mechanism involving the NagY antiterminator and the ribonuclease RNase III. In addition, we identified the target genes of the regulator, through which we were able to demonstrate that NagY has a strong impact on the metabolism of β-glucosides. Overall, this work highlights the importance of regulation of the bacterial metabolic adaptation in the host.