Regulation of mannitol metabolism inEnterococcus faecalisand association withparEF0409toxin-antitoxin locus function

Abstract

AbstractTheparEF0409type I toxin-antitoxin locus is situated between genes for two paralogous mannitol-family phosphoenolpyruvate phosphotransferase systems (PTS). In order to address the possibility thatparEF0409function was associated with sugar metabolism, genetic and phenotypic analyses were performed on the flanking genes. It was found that the genes were transcribed as two operons; the downstream operon essential for mannitol transport and metabolism and the upstream operon performing a regulatory function. In addition to genes for the PTS components, the upstream operon encodes a gene similar tomtlR, the key regulator of mannitol metabolism in other Gram-positive bacteria. We confirmed that this gene is essential for regulation of the downstream operon and identified putative phosphorylation sites required for carbon catabolite repression and mannitol-specific regulation. Genomic comparisons revealed that this dual operon organization of mannitol utilization genes is uncommon in enterococci and that association with a toxin-antitoxin system is unique toE. faecalis. Finally, we consider possible links betweenparEF0409function and mannitol utilization.ImportanceEnterococcus faecalisis both a common member of the human gut microbiota and an opportunistic pathogen. Its evolutionary success is partially due to its metabolic flexibility: in particular, its ability to import and metabolize a wide variety of sugars. While a large number of phosphoenolpyruvate phosphotransferase sugar transport systems have been identified in theE. faecalisgenome bioinformatically, the specificity and regulation of most of these systems remains undetermined. Here we characterize a complex system of two operons flanking a type I toxin-antitoxin system required for the transport and metabolism of the common dietary sugar mannitol. We also determine the phylogenetic distribution of mannitol utilization genes in the enterococcal genus and discuss the significance of association with toxin-antitoxin systems.