The cell wall hydrolase MltG is essential to maintain cell wall homeostasis of <i>Enterococcus faecalis</i>

<i>Enterococcus faecalis</i> is an opportunistic pathogen that colonizes the human gut microbiome. Infections caused by <i>E. faecalis</i> are increasingly prevalent and difficult to treat due to the multidrug resistance exhibited toward common clinical antibiotics. A thorough understanding of the mechanisms used by <i>E. faecalis</i> to maintain cell wall homeostasis will serve as a foundation for future development of new therapeutics that disable enterococcal resistance to cell-wall-active antibiotics and may reveal new vulnerabilities that could be exploited by novel antimicrobials. Here, we demonstrate that the MltG peptidoglycan hydrolase is essential for enterococcal cell wall homeostasis, but that the enzymatic activity of MltG is not required for this role. Instead, the enzymatic activity of MltG impacts intrinsic resistance toward cephalosporins.