Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Microbiol Spectr. 2022 Jun 29;10(3):e0180621. doi: 10.1128/spectrum.01806-21. Epub 2022 May 23.
Bacteriocins have been applied in the food industries and have become promising next-generation antibiotics. Some bacteria produce bacteriocins and possess immunity factors for self-protection. Nisin A, a bacteriocin produced by Lactococcus lactis, shows broad-spectrum activity. However, the evolution and cross-resistance ability of the immunity factors in some species results in reduced susceptibility to bacteriocins. Here, we investigated the elements responsible for nisin A resistance in Streptococcus mutans and their contribution to mutacins (bacteriocins produced by S. mutans) resistance. We classified the nisin A-resistance regions into six types based on the different combinations of 3 immunity factors, and , and the presence of mutacin synthesis operon upstream of . Data shows that NsrX effectively acts against nisin A but not mutacins, while the newly identified ABC transporter MutHIJ acts against three mutacins but not nisin A. Three types of MutFEG are identified based on their amino acid sequences: α (in Nsr-types C and D-I), β (in Nsr-types B and d-III), and γ (in Nsr-type E). MutFEG-α strongly contributes to mutacin I resistance, while MutFEG-β and MutFEG-γ strongly contribute to mutacin III, IIIb, and nisin A resistance. Additionally, -like structures could be found in various streptococcal species isolated from the oral cavity of humans, chimpanzees, monkeys, bears, and hamsters. Our findings suggest that immunity factors rearrange and adapt in the presence of bacteriocins and could be transferred among closely related species, thus altering the bacterial competition within the microflora. Streptococcus mutans is an important organism of oral microbiota and associated with dental caries and systemic diseases such as stroke and endocarditis. They produce bacteriocins known as mutacins to compete with other oral bacteria and possess immune factors for self-protection. We found that the nisin A and mutacins resistance patterns correlated with the immunity components and MutFEG variants, and the genetic difference was driven by the insertion of mutacin-synthesis cassettes. Our study provides an understanding of the development of bacteriocin resistance among streptococcal species, which may alter the bacterial interaction and ecology within the oral biofilm.
细菌素已应用于食品工业，并成为有前途的下一代抗生素。一些细菌产生细菌素，并拥有自我保护的免疫因子。乳球菌产生的细菌素乳链菌肽 A 具有广谱活性。然而，某些物种中免疫因子的进化和交叉耐药能力导致对细菌素的敏感性降低。在这里，我们研究了导致变形链球菌对乳链菌肽 A 耐药的因素及其对mutacins（变形链球菌产生的细菌素）耐药性的贡献。我们根据 3 种不同免疫因子的组合以及 和 的存在，将乳链菌肽 A 耐药区域分为 6 种类型，并在 的上游存在 mutacin 合成操纵子。数据表明，NsrX 有效对抗乳链菌肽 A，但不针对 mutacins，而新鉴定的 ABC 转运蛋白 MutHIJ 则针对 3 种 mutacins，但不针对乳链菌肽 A。根据氨基酸序列，鉴定了三种类型的 MutFEG：α（在 Nsr 型 C 和 D-I 中）、β（在 Nsr 型 B 和 d-III 中）和 γ（在 Nsr 型 E 中）。MutFEG-α 强烈促进 mutacin I 耐药性，而 MutFEG-β 和 MutFEG-γ 强烈促进 mutacin III、IIIb 和乳链菌肽 A 耐药性。此外，在从人类、黑猩猩、猴子、熊和仓鼠口腔中分离的各种链球菌物种中可以发现类似 -like 的结构。我们的研究结果表明，在细菌素存在的情况下，免疫因子会发生重排和适应，并可以在密切相关的物种之间转移，从而改变微生物群内的细菌竞争。变形链球菌是口腔微生物群的重要组成部分，与龋齿和中风、心内膜炎等系统性疾病有关。它们产生被称为 mutacins 的细菌素来与其他口腔细菌竞争，并拥有自我保护的免疫因子。我们发现，乳链菌肽 A 和 mutacins 耐药模式与免疫成分和 MutFEG 变体相关，遗传差异是由 mutacin 合成盒的插入驱动的。我们的研究提供了对链球菌种中细菌素耐药性发展的理解，这可能会改变口腔生物膜内的细菌相互作用和生态。
