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

Abstract

Enterococci are Gram-positive bacteria present in the healthy human microbiota, but they are also a leading cause of nosocomial infections. Maltodextrins utilization by Enterococcus faecalis has been identified as an important factor for colonization of mammalians hosts. Here we show that the LacI/GalR transcriptional regulator MalR, the maltose genes regulator, is also the main regulator of the operons encoding an ABC transporter (mdxEFG) and three metabolic enzymes (mmdH-gmdH-mmgT) required for the uptake and catabolism of maltotetraose and longer maltodextrins. The utilization of maltose and maltodextrins is consequently coordinated and induced by the disaccharide maltose, which binds to MalR. Carbon catabolite repression of the mdxEFG and mmdH-gmdH-mmgT operons is mediated by both, P-Ser-HPr/MalR and P-Ser-HPr/CcpA. The latter complex exerts only moderate catabolite repression which became visible when comparing maltodextrin operon expression in a malR- and a malR-ΔccpA double mutant grown in the presence of maltose, which is transported via a phosphotransferase system and thus favours the formation of P-Ser-HPr. Moreover, maltodextrin transport via MdxEFG slows rapidly when glucose is added, suggesting an additional regulation via inducer exclusion. This complex regulation of metabolic operons likely allows E. faecalis to fine-tune gene expression in response to changing environmental conditions. IMPORTANCE Enterococcus faecalis represents a leading cause of hospital acquired infections worldwide. Several studies highlighted the importance of carbohydrate metabolism in the infection process of this bacterium. The genes required for maltodextrin metabolism are particularly induced during mice infection and therefore should play an important role for pathogenesis. Since no data were hitherto available concerning the regulation of expression of the maltodextrin operons, we have conducted experiments to study the underlying mechanisms.

The role of the universal sugar transport system components PtsI (EI) and PtsH (HPr) in Enterococcus faecium

“…This may mean that PTS are not used to transport these sugars, or that there is a high-affinity, non-PTS system that compensates for the loss of PTS. In low G+C gram-positive bacteria, CcpA, PtsH (HPr), and bifunctional HPr kinase/phosphatase (HPrK/P) are involved in global transcriptional regulation of carbon catabolite repression (CCR) (Grand et al 2020 ). The inability to activate CCR due to the absence of PtsH (HPr) in the ∆ ptsHI mutant could be a confounding factor stemming from its reduced ability to regulate gene expression.…”

Pervasive selective sweeps across human gut microbiomes

“…We detected a total of 8 distinct peaks in this species, in line with the typical number of peaks observed per species in our dataset. The tallest peak coincides with the genes mdxE and mdxF , which are ATP-binding cassette transporters involved in metabolizing maltodextrin [46]. R. bromii was not alone in exhibiting peaks containing genes related to maltodextrin metabolism: 3 other species ( E. rectale, E. siraeum , and B. cellulosilyticus ) also had peaks overlapping maltodextrin-related genes (Table S4).…”

CcpA mutants influence selective carbon source utilization by changing interactions with target genes in Bacillus licheniformis

“…Over the past few years, the function of CcpA has been investigated extensively [52,53]. Many studies have been performed [54,55] to explore the relationship between structure and function of CcpA.…”