Davey Lauren, Halperin Scott A, Lee Song F
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada Department of Pediatrics, Faculty of Medicine, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.
J Bacteriol. 2015 Nov 2;198(2):321-31. doi: 10.1128/JB.00800-15. Print 2016 Jan 15.
Streptococcus gordonii is a commensal inhabitant of the human oral cavity. To maintain its presence as a major component of oral biofilms, S. gordonii secretes inhibitory molecules such as hydrogen peroxide and bacteriocins to inhibit competitors. S. gordonii produces two nonmodified bacteriocins (i.e., Sth1 and Sth2) that are regulated by the Com two-component regulatory system, which also regulates genetic competence. Previously we found that the thiol-disulfide oxidoreductase SdbA was required for bacteriocin activity; however, the role of SdbA in Com signaling was not clear. Here we demonstrate that ΔsdbA mutants lacked bacteriocin activity because the bacteriocin gene sthA was strongly repressed and the peptides were not secreted. Addition of synthetic competence-stimulating peptide to the medium reversed the phenotype, indicating that the Com pathway was functional but was not activated in the ΔsdbA mutant. Repression of bacteriocin production was mediated by the CiaRH two-component system, which was strongly upregulated in the ΔsdbA mutant, and inactivation of CiaRH restored bacteriocin production. The CiaRH-induced protease DegP was also upregulated in the ΔsdbA mutant, although it was not required for inhibition of bacteriocin production. This establishes CiaRH as a regulator of Sth bacteriocin activity and links the CiaRH and Com systems in S. gordonii. It also suggests that either SdbA or one of its substrates is an important factor in regulating activation of the CiaRH system.
Streptococcus gordonii is a noncariogenic colonizer of the human oral cavity. To be competitive in the oral biofilm, S. gordonii secretes antimicrobial peptides called bacteriocins, which inhibit closely related species. Our previous data showed that mutation of the disulfide oxidoreductase SdbA abolished bacteriocin production. In this study, we show that mutation of SdbA generates a signal that upregulates the CiaRH two-component system, which in turn downregulates a second two-component system, Com, which regulates bacteriocin expression. Our data show that these systems are also linked in S. gordonii, and the data reveal that the cell's ability to form disulfide bonds is sensed by the CiaRH system.
戈登氏链球菌是人类口腔中的共生菌。为了作为口腔生物膜的主要成分维持其存在，戈登氏链球菌分泌抑制性分子，如过氧化氢和细菌素，以抑制竞争者。戈登氏链球菌产生两种未修饰的细菌素（即Sth1和Sth2），它们受Com双组分调节系统调控，该系统也调节遗传感受态。此前我们发现硫醇-二硫键氧化还原酶SdbA是细菌素活性所必需的；然而，SdbA在Com信号传导中的作用尚不清楚。在此我们证明，ΔsdbA突变体缺乏细菌素活性，因为细菌素基因sthA受到强烈抑制且肽未分泌。向培养基中添加合成的感受态刺激肽可逆转该表型，表明Com途径功能正常，但在ΔsdbA突变体中未被激活。细菌素产生的抑制由CiaRH双组分系统介导，该系统在ΔsdbA突变体中强烈上调，CiaRH失活可恢复细菌素产生。CiaRH诱导的蛋白酶DegP在ΔsdbA突变体中也上调，尽管它不是抑制细菌素产生所必需的。这确立了CiaRH作为Sth细菌素活性的调节因子，并将戈登氏链球菌中的CiaRH和Com系统联系起来。这也表明SdbA或其底物之一是调节CiaRH系统激活的重要因素。
戈登氏链球菌是人类口腔中的非致龋定植菌。为了在口腔生物膜中具有竞争力，戈登氏链球菌分泌称为细菌素的抗菌肽，其抑制密切相关的物种。我们之前的数据表明，二硫键氧化还原酶SdbA的突变消除了细菌素的产生。在本研究中，我们表明SdbA的突变产生了一个信号，该信号上调CiaRH双组分系统，而CiaRH双组分系统又下调调节细菌素表达的第二个双组分系统Com。我们的数据表明，这些系统在戈登氏链球菌中也相互关联，并且数据揭示细胞形成二硫键的能力由CiaRH系统感知。
