Enterococcus faecalis MalR acts as a repressor of the maltose operons and additionally mediates their catabolite repression via direct interaction with seryl‐phosphorylated‐HPr

Abstract

Enterococci are gram‐positive pathogens and lead to cause hospital‐acquired infections worldwide. Central carbon metabolism was shown as highly induced in Enterococcus faecalis during infection context. Metabolism of α‐polysaccharides was previously described as an important factor for host colonisation and biofilm formation. A better characterisation of the adaptation of this bacterium to carbohydrate availabilities may lead to a better understanding of the link between carbohydrate metabolism and the infection process of E. faecalis. Here we show that MalR, a LacI/GalR transcriptional regulator, is the main factor in the regulation of the two divergent operons involved in maltose metabolism in this bacterium. The malR gene is transcribed from the malP promoter, but also from an internal promoter inside the gene located upstream of malR. In the absence of maltose, MalR acts as a repressor and in the presence of glucose, it exerts efficient CcpA‐independent carbon catabolite repression. The central PTS protein P‐Ser‐HPr interacts directly with MalR and enhances its DNA binding capacity, which allows E. faecalis to adapt its metabolism to environmental conditions.

Enterococcus faecalis Maltodextrin Gene Regulation by Combined Action of Maltose Gene Regulator MalR and Pleiotropic Regulator CcpA

“…1B) were identified between the two later operons. These motifs are similar to the operator sites of the two maltose operons, which are recognized by MalR (22). We, therefore, presumed that MalR might also regulate the maltodextrin genes.…”

“…When searching for MdxR homologs in E. faecalis genomes, we found that most strains, including V583 and OG1RF (used in this study), contain only proteins with weak sequence identity (less than 30%), suggesting that different regulation mechanisms are operative in the two species. MalR was shown to specifically bind to DNA sequences preceding the two mal operons, which had the following consensus: CGMAACCGAT TGCR (22). Interestingly, we detected similar motifs upstream of the E. faecalis maltodextrin genes, suggesting that MalR might also directly regulate the expression of the two maltodextrin operons.…”

“…The metabolism of maltose and maltodextrins in E. faecalis, therefore, appears to be tightly connected. In a previous study (22), we showed that the maltose genes are regulated by MalR, a LacI/GalR family transcriptional regulator. These maltose genes were shown to be submitted to carbon catabolite repression (CCR) when the cells were grown in the presence of glucose (22).…”

“…In a previous study (22), we showed that the maltose genes are regulated by MalR, a LacI/GalR family transcriptional regulator. These maltose genes were shown to be submitted to carbon catabolite repression (CCR) when the cells were grown in the presence of glucose (22). CCR of the maltose genes was independent of the catabolite control protein A (CcpA), the main regulator of CCR in Firmicutes (23).…”

“…In this phosphorylation cascade, the HPr protein is phosphorylated on His-15 (PϳHis-HPr), but as mentioned above, this protein also carries an additional phosphorylatable seryl residue (Ser-46). Interestingly, P-Ser-HPr of E. faecalis was found to interact not only with CcpA but also with MalR (22). In addition, MalR was found to be required for CCR of the maltose genes likely mediated by the P-Ser-HPr/MalR complex.…”