Core Technology Research Department, Central R&D Laboratory, Kobayashi Pharmaceutical Co., Ltd.
J Microorg Control. 2024;29(1):27-31. doi: 10.4265/jmc.29.1_27.
Cutibacterium acnes is an opportunistic pathogen in acne vulgaris. C. acnes produces autoinducer-2 (AI-2), a signaling molecule used for communication known as quorum sensing (QS). In C. acnes, QS reportedly upregulates biofilm formation leading to resistance against bactericidal agents. In this study, we analyzed how heparinoid affected QS and biofilm formation of the opportunistic pathogen C. acnes. We also verified whether heparinoid would suppress biofilm formation and enhance the efficacy of the bactericidal agent 4-isopropyl-3-methylphenol (IPMP) against C. acnes biofilms. We ran an AI-2 bioassay using Vibrio harveyi ATCC BBA-1121. Heparinoid exhibited inhibitory activity against AI-2 at concentrations of 0.003-0.005%, suggesting an AI-2 analog-derived or C. acnes culture supernatant-derived inhibition of the AI-2 activity. To evaluate how heparinoid suppresses biofilm formation in C. acnes, we completed a biofilm assay in 96-well plates. We also evaluated the bactericidal activity of IPMP against the C. acnes biofilm prepared with or without heparinoid. Heparinoid inhibited C. acnes biofilm formation and IPMP bactericidal efficacy increased upon heparinoid-mediated suppression of biofilm formation. In this study, we clarified that heparinoid inhibits the AI-2-mediated QS of C. acnes, thereby suppressing biofilm formation and increasing IPMP bactericidal efficacy, potentially suppressing acne vulgaris.
痤疮丙酸杆菌是寻常痤疮的机会致病菌。痤疮丙酸杆菌产生自诱导因子-2(AI-2),这是一种用于群体感应(QS)的信号分子。据报道,在痤疮丙酸杆菌中,QS 上调生物膜形成,导致对杀菌剂的耐药性。在这项研究中,我们分析了肝素类似物如何影响机会致病菌痤疮丙酸杆菌的 QS 和生物膜形成。我们还验证了肝素类似物是否会抑制生物膜形成并增强杀菌剂 4-异丙基-3-甲基苯酚(IPMP)对痤疮丙酸杆菌生物膜的功效。我们使用哈维弧菌 ATCC BBA-1121 进行了 AI-2 生物测定。肝素类似物在 0.003%-0.005%的浓度下表现出对 AI-2 的抑制活性,表明 AI-2 活性受到 AI-2 类似物或痤疮丙酸杆菌培养上清液的抑制。为了评估肝素类似物如何抑制痤疮丙酸杆菌的生物膜形成,我们在 96 孔板上完成了生物膜测定。我们还评估了 IPMP 对有无肝素类似物制备的痤疮丙酸杆菌生物膜的杀菌活性。肝素类似物抑制了痤疮丙酸杆菌生物膜的形成,并且 IPMP 的杀菌效力在肝素类似物介导的生物膜形成抑制作用下增加。在这项研究中,我们阐明了肝素类似物抑制了痤疮丙酸杆菌的 AI-2 介导的 QS,从而抑制了生物膜形成并提高了 IPMP 的杀菌效力,可能抑制了寻常痤疮。
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