Seryl-phosphorylated HPr regulates CcpA-independent carbon catabolite repression in conjunction with PTS permeases in Streptococcus mutans.

Carbohydrate catabolite repression (CCR) in Streptococcus mutans can be independent of catabolite control protein A (CcpA) and requires specific components of phosphoenolpyruvate-dependent sugar:phosphotransferase system (PTS) permeases. Here, the effects of various ptsH (HPr) and hprK (HPr kinase/phosphatase) mutations on growth and CCR were evaluated. An hprKV265F mutation, which enhanced Ser46 phosphorylation of HPr, inhibited growth on multiple PTS sugars. A ptsHS46A mutation reversed the effects of hprKV265F in most cases. A strain carrying a ptsHS46D mutation, which mimics HPr(Ser-P), presented with more severe growth defects than the hprKV265F mutant. The hprKV265F mutant enhanced CCR of the fruA and levD operons, a phenotype reversible by the ptsHS46A mutation. The effects of the hprKV265F mutation on fruA and levD expression were independent of CcpA, but dependent on ManL (IIAB(Man)) and, to a lesser extent, on FruI (IIABC(Fru)), in a carbohydrate-specific fashion. Expression of the Bacillus subtilis ptsG gene in the manL mutant did not restore CCR of the lev or fru operons. The hprKV265F mutation inhibited growth on cellobiose and lactose, but only the transcription of the cel operon was decreased. Thus, in S. mutans, serine-phosphorylated HPr functions in concert with particular PTS permeases to prioritize carbohydrate utilization by modulating sugar transport and transcription of catabolic operons.