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 produced by Staphylococcus epidermidis Tu3298 and S. gallinarum Tu3928, respectively. The epidermin biosynthetic genes involved in maturation, regulation, and immunity have been identified previously. How epidermin or gallidermin is secreted, however, has remained unclear. Here, we characterize two additional genes, epiH and epiT, as well as the homologous gallidermin genes gdmH and gdmT. EpiT and GdmT are similar to one-component ABC transporters that are involved in the secretion of proteins or peptides. EpiH and GdmH are hydrophobic proteins without conspicuous similarities to other proteins. Comparison of the gene sequences revealed that epiT is incomplete, having an internal deletion that causes a frame shift and a second deletion at the 3'-end, while gdmT is intact. Introduction of epiT and epiH into the heterologous host S. carnosus (pTepi14) bearing the maturation and regulation genes had no significant effect on the rather low level of epidermin production. The presence of the homologous gdmT and gdmH, however, resulted in a strong increase (seven- to tenfold) in the production level, which is very likely to be due to increased efficiency of epidermin secretion. Both gdmT and gdmH were necessary for this effect, indicating that the two gene products cooperate in some way. In the epidermin-producing wild-type strain Tu3298, which contains epiH and the disrupted epiT, the addition of gdmT alone led to a two-fold increase in epidermin production. Both gdmT and gdmH and the corresponding epi genes were activated by the transcriptional regulator EpiQ; this is in accordance with the presence of putative EpiQ operator sites in the promoter regions.