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Staphylococcus aureus  uses two-component systems (TCSs) to adapt to stressful environmental conditions. To colonize a host,  S. aureus  must resist bacteriocins produced by commensal bacteria. In a comprehensive analysis using individual TCS inactivation mutants, the inactivation of two TCSs,  graRS  and  braRS , significantly increased the susceptibility to the class I bacteriocins, nukacin ISK-1 and nisin A, and inactivation of  vraSR  slightly increased the susceptibility to nukacin ISK-1. In addition, two ABC transporters (BraAB and VraDE) regulated by BraRS and one transporter (VraFG) regulated by GraRS were associated with resistance to nukacin ISK-1 and nisin A. We investigated the role of these three TCSs of  S. aureus  in co-culture with  S. warneri , which produces nukacin ISK-1, and  Lactococcus lactis , which produces nisin A. When co-cultured with  S. warneri  or  L. lactis , the  braRS  mutant showed a significant decrease in its population compared with the wild-type, whereas the  graRS  and  vraSR  mutants showed slight decreases. Expression of  vraDE  was elevated significantly in  S. aureus  co-cultured with nisin A/nukacin ISK-1-producing strains. These results suggest that three distinct TCSs are involved in the resistance to nisin A and nukacin ISK-1. Additionally,  braRS  and its related transporters played a central role in  S. aureus  survival in co-culture with the strains producing nisin A and nukacin ISK-1.

Three Distinct Two-Component Systems Are Involved in Resistance to the Class I Bacteriocins, Nukacin ISK-1 and Nisin A, in Staphylococcus aureus