SECRETION OF THE LANTIBIOTICS EPIDERMIN AND GALLIDERMIN - SEQUENCE-ANALYSIS OF THE GENES GDMT AND GDMH, THEIR INFLUENCE ON EPIDERMIN PRODUCTION AND THEIR REGULATION BY EPIQ

The closely related lantibiotics epidermin and gallidermin are produce d by Staphylococcus epidermidis Tu3298 and S. gallinarum Tu3928, respe ctively. The epidermin biosynthetic genes involved in maturation, regu lation, and immunity have been identified previously. How epidermin or gallidermin is secreted, however, has remained unclear. Here, we char acterize two additional genes, epiH and epiT, as well as the homologou s gallidermin genes gdmH and gdmT. EpiT and GdmT are similar to one-co mponent ABC transporters that are involved in the secretion of protein s or peptides. EpiH and GdmH are hydrophobic proteins without conspicu ous similarities to other proteins. Comparison of the gene sequences r evealed that epiT is incomplete, having an internal deletion that caus es a frame shift and a second deletion at the 3'-end, while gdmT is in tact. Introduction of epiT and epiH into the heterologous host S. carn osus (pTepil4) bearing the maturation and regulation genes had no sign ificant effect on the rather low level of epidermin production. The pr esence of the homologous gdmT and gdmH, however, resulted in a strong increase (seven- to tenfold) in the production level, which is very li kely to be due to increased efficiency of epidermin secretion. Both gd mT and gdmH were necessary for this effect, indicating that the two ge ne products cooperate in some way. In the epidermin-producing wild-typ e strain Tu3298, which contains epiH and the disrupted epiT, the addit ion of gdmT alone led to a two-fold increase in epidermin production. Both gdmT and gdmH and the corresponding epi genes were activated by t he transcriptional regulator EpiQ; this is in accordance with the pres ence of putative EpiQ operator sites in the promoter regions.