title: Two-Component Systems Involved in Susceptibility to Nisin A in Streptococcus pyogenes.
abstract: Two-component systems (TCSs) are regulatory systems in bacteria that play important roles in sensing and adapting to the environment. In this study, we systematically evaluated the roles of TCSs in the susceptibility of the group A Streptococcus (GAS; Streptococcus pyogenes) SF370 strain to several types of lantibiotics. Using individual TCS deletion mutants, we found that the deletion of srtRK (spy_1081-spy_1082) in SF370 increased the susceptibility to nisin A, which is produced by Lactococcus lactis ATCC 11454, but susceptibility to other types of lantibiotics (nukacin ISK-1, produced by Staphylococcus warneri, and staphylococcin C55, produced by Staphylococcus aureus) was not altered in the TCS mutants tested. The expression of srtFEG (spy_1085 to spy_1087), which is located downstream of srtRK and is homologous to ABC transporters, was increased in response to nisin A. However, srtEFG expression was not induced by nisin A in the srtRK mutant. The inactivation of srtFEG increased the susceptibility to nisin A. These results suggest that SrtRK controls SrtFEG expression to alter the susceptibility to nisin A. Further experiments showed that SrtRK is required for coexistence with L. lactis ATCC 11454, which produces nisin A. Our results elucidate the important roles of S. pyogenes TCSs in the interactions between different bacterial species, including bacteriocin-producing bacteria.
  
  
  
  In this study, we focused on the association of TCSs with susceptibility to bacteriocins in S. pyogenes SF370, which has no ability to produce bacteriocins, and reported two major new findings. We demonstrated that the SrtRK TCS is related to susceptibility to nisin A by controlling the ABC transporter SrtFEG. We also showed that S. pyogenes SrtRK is important for survival when the bacteria are cocultured with nisin A-producing Lactococcus lactis This report highlights the roles of TCSs in the colocalization of bacteriocin-producing bacteria and non-bacteriocin-producing bacteria. Our findings provide new insights into the function of TCSs in S. pyogenes.
authors.affiliation: Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kawada-Matsuo
authors.affiliation: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.affiliation: Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Arii
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Zendo
authors.affiliation: Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oogai
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan Research and Education Center for Advanced Oral Science, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sonomoto
authors.affiliation: Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan Research and Education Center for Advanced Oral Science, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan hkomatsu@dent.kagoshima-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komatsuzawa
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001430:Bacteriocins / Q000096:biosynthesis / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D009561:Nisin / Q000096:biosynthesis / Q000494:pharmacology*; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D001430:Bacteriocins; C421186:nukacin ISK-1; D009561:Nisin; C017724:staphylococcin; C102526:nisin A