Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Orthodontics and Dentofacial Orthopedics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Appl Environ Microbiol. 2020 Apr 1;86(8). doi: 10.1128/AEM.02923-19.
Nisin A is a bacteriocin produced by and is widely used as a food preservative. has the BraRS-VraDE system that provides resistance against low concentrations of nisin A. BraRS is a two-component system that induces the expression of the ABC transporter VraDE. Previously, we isolated a highly nisin A-resistant strain with increased VraDE expression due to a mutation in In this study, we isolated MW2 mutants with BraRS-VraDE-independent nisin A resistance. These mutants, designated SAN2 ( isin resistant) and SAN469, had a mutation in , which encodes a transcriptional regulator responsible for the expression of the operon. As a result, these mutants exhibited increased expression of PmtABCD, a transporter responsible for the export of phenol-soluble modulin (PSM). Characterization of the mutants revealed that they have decreased susceptibility to human β-defensin-3 (hBD3) and LL37, which are innate immune factors. Additionally, these mutants showed higher hemolytic activity than the original MW2 strain. Furthermore, in a mouse bacteremia model, the SAN2 strain exhibited a lower survival rate than the original MW2 strain. These results indicate that the increased expression of due to a mutation is an alternative nisin A resistance mechanism that also affects virulence in Recently, the emergence of antibiotic-resistant bacteria has resulted in serious problems for chemotherapy. In addition, many antibacterial agents, such as disinfectants and food additives, are widely used. Therefore, there is a possibility that bacteria are becoming resistant to some antibacterial agents. In this study, we investigated whether can become resistant to nisin A, one of the bacteriocins applied as a food additive. We isolated a highly nisin A-resistant strain designated SAN2 that displayed increased expression of Pmt proteins, which are involved in the secretion of virulence factors called phenol-soluble modulins (PSMs). This strain also showed decreased susceptibility to human antimicrobial peptides and increased hemolytic activity. In addition, SAN2 showed increased lethal activity in a mouse bacteremia model. Our study provides new insights into the possibility that the acquisition of resistance against food preservatives may modulate virulence in , suggesting that we need to pay more attention to the use of food preservatives together with antibiotics.
乳链菌肽 A 是由 产生的细菌素，被广泛用作食品防腐剂。 具有 BraRS-VraDE 系统，可提供对低浓度乳链菌肽 A 的抗性。BraRS 是一种双组分系统，可诱导 ABC 转运体 VraDE 的表达。之前，我们由于 中的突变而分离出一种对乳链菌肽 A 高度抗性的菌株，该菌株表达增加了 VraDE。在这项研究中，我们分离出了 BraRS-VraDE 不依赖的乳链菌肽 A 抗性的 MW2 突变体。这些突变体，命名为 SAN2（对乳链菌肽 A 具有抗性）和 SAN469，在 中发生突变，该基因编码负责 操纵子表达的转录调节剂。结果，这些突变体表现出对负责酚溶性调节素（PSM）外排的转运蛋白 PmtABCD 的表达增加。突变体的表征表明，它们对人 β-防御素-3（hBD3）和 LL37 的敏感性降低，这是先天免疫因子。此外，这些突变体比原始 MW2 菌株表现出更高的溶血活性。此外，在小鼠菌血症模型中，SAN2 菌株的存活率低于原始 MW2 菌株。这些结果表明，由于 中的突变导致的 表达增加是一种替代的乳链菌肽 A 抗性机制，也会影响 的毒力。最近，抗生素耐药菌的出现给化疗带来了严重问题。此外，许多抗菌剂，如消毒剂和食品添加剂，被广泛使用。因此，细菌对抗菌剂的耐药性有可能增加。在这项研究中，我们研究了 是否可以对乳链菌肽 A 产生耐药性，乳链菌肽 A 是作为食品添加剂应用的一种细菌素。我们分离出了一种高度耐乳链菌肽 A 的菌株，命名为 SAN2，该菌株表现出参与分泌称为酚溶性调节素（PSMs）的毒力因子的 Pmt 蛋白表达增加。该菌株还表现出对人抗菌肽的敏感性降低和溶血活性增加。此外，SAN2 在小鼠菌血症模型中表现出更高的致死活性。我们的研究提供了新的见解，即获得对食品防腐剂的耐药性可能会调节 中的毒力，这表明我们需要更加注意食品防腐剂与抗生素的联合使用。
