THE GROUP-A STREPTOCOCCAL DIPEPTIDE PERMEASE (DPP) IS INVOLVED IN THEUPTAKE OF ESSENTIAL AMINO-ACIDS AND AFFECTS THE EXPRESSION OF CYSTEINE PROTEASE

The majority of characterized bacterial dipeptide permeases (Dpp) are membrane-associated complexes of five proteins belonging to the ABC-tr ansporter family, They have been found to be involved in the uptake of essential amino acids, haem production, chemotaxis and sporulation. A 5.8 kb genomic DNA fragment of the serotype M49 group A streptococcal (GAS) strain CS101 was sequenced and found to contain five putative G AS Dpp genes (dppA to dppE), Deduced amino acid sequences exhibited 17 -54% similarity to corresponding ABC-transporter sequences, The operon organization of the five genes was confirmed by transcriptional analy sis, and a shorter, more abundant, dppA-only transcript was detected s imilar to that found in the GAS oligopeptide permease (Opp) system, In sertional inactivation was used to create serotype M2 and M49 strains that did not express the dppD and dppEATPase genes or nearly the entir e operon, In feeding experiments with di- to hexapeptides, the wild-ty pe strain grew with each peptide tested. The dpp mutants were unable t o grow on dipeptides, whereas hexapeptides did not sustain the growth of dpp mutants, Expression of the dpp operon was induced approximately fourfold in late exponential growth phase. In addition, a striking in crease in the dppA to dppA-E ratio from 5:1 to more than 20:1 occurred during late exponential growth phase in complex medium. Growth in che mically defined medium (CDM) supplemented with various dipeptides spec ifically induced the expression of dpp and reduced both the dppA to dp pA-E and oppA to oppA-FmRNA ratios, Expression of the virulence factor SpeB (major cysteine protease) was reduced eightfold in dpp mutants, whereas dpp expression was decreased about fourfold in a Mga virulence regulator mutant, Taken together, these data indicate a correlation b etween levels of intracellular essential amino acids and the regulatio n of virulence factor expression.