A Novel Type of Immunity Protein, NukH, for the Lantibiotic Nukacin ISK-1 Produced by Staphylococcus warneriISK-1

Staphylococcus warneriISK-1 produces a lantibiotic, nukacin ISK-1. The nukacin ISK-1 gene cluster consists of at least six genes, nukA, -M, -T, -F, -E, and -G, and two open reading frames, ORF1 and ORF7 (designated nukH). Sequence comparisons suggested that NukF, -E, -G, and -H contribute to immunity to nukacin ISK-1. We investigated the immunity levels of recombinant Lactococcus lactisexpressing nukFEGand nukHagainst nukacin ISK-1. The co-expression of nukFEGand nukHresulted in a high degree of immunity. The expression of either nukFEGor nukHconferred partial immunity against nukacin ISK-1. These results suggest that NukH contributes cooperatively to self-protection with NukFEG. The nukacin ISK-1 immunity system might function against another lantibiotic, lacticin 481. Western blot analysis showed that NukH expressed in Staphylococcus carnosuswas localized in the membrane. Peptide release/bind assays indicated that the recombinant L. lactisexpressing nukHinteracted with nukacin ISK-1 and lacticin 481 but not with nisin A. These findings suggest that NukH contributes cooperatively to host immunity as a novel type of lantibiotic-binding immunity protein with NukFEG.