S-aryl-L-cysteine sulphoxides and related organosulphur compounds alter oral biofilm development and AI-2-based cell-cell communication.
S-aryl-L-cysteine sulphoxides and related organosulphur compounds alter oral biofilm development and AI-2-based cell-cell communication.
复制标题
S-芳基-L-半胱氨酸亚砜和相关有机硫化合物改变口腔生物膜发育和基于 AI-2 的细胞间通讯。
DOI：
10.1111/jam.12616
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发表时间：
2014
影响因子：
4
通讯作者：
Cady,NC
中科院分区：
文献类型：
--
作者：
Kasper,SH;Samarian,D;Jadhav,AP;Rickard,AH;Musah,RA;Cady,NC
目的设计和合成一个结构相关的小分子库，这些小分子与植物大蒜素产生的化合物的同系物相关，并确定它们干扰口腔细菌AI-2细胞间通讯和生物膜形成的能力。许多人类疾病与持久性细菌生物膜有关。口腔生物膜（牙菌斑）是有问题的，因为它们往往与蛀牙，牙周病和全身性疾病，如心脏病和diabetes.Methods和ResultsUsing一个基于微孔板的方法，生物启发的小分子库进行了筛选抗生物膜活性对口腔菌种变形链球菌UA 159，链球菌sanguis 10556和放线菌orisMG 1。为了补充静态筛选，还在代表人类口腔的条件下进行了基于流动的BioFlux微流体系统筛选。发现几种化合物在所有三种测试的口腔细菌中显示生物膜抑制活性。这些化合物也被证明可以抑制哈维氏弧菌的生物发光，因此被推断为群体感应（quorum sensing，QS）抑制剂。结论由于这些化合物彼此之间的结构相似性，以及AI-2生物合成途径中的关键分子，我们认为这些分子可能通过拮抗QS或QS相关途径来减少生物膜的形成。研究的意义和影响这项研究强调了潜在的基于非抗菌剂的策略，专注于AI-2细胞-细胞信号传导，以控制牙菌斑的发展。考虑到许多细菌物种使用AI-2细胞-细胞信号传导，以及对医疗保健产品中使用抗菌剂的日益关注，这种抗生物膜方法也可用于控制人类口腔以外环境中的生物膜。
AimsTo design and synthesize a library of structurally related, small molecules related to homologues of compounds produced by the plantPetiveria alliaceaand determine their ability to interfere with AI‐2 cell–cell communication and biofilm formation by oral bacteria. Many human diseases are associated with persistent bacterial biofilms. Oral biofilms (dental plaque) are problematic as they are often associated with tooth decay, periodontal disease and systemic disorders such as heart disease and diabetes.Methods and ResultsUsing a microplate‐based approach, a bio‐inspired small molecule library was screened for anti‐biofilm activity against the oral speciesStreptococcus mutansUA159, Streptococcus sanguis10556 andActinomyces orisMG1. To complement the static screen, a flow‐based BioFlux microfluidic system screen was also performed under conditions representative of the human oral cavity. Several compounds were found to display biofilm inhibitory activity in all three of the oral bacteria tested. These compounds were also shown to inhibit bioluminescence byVibrio harveyiand were thus inferred to be quorum sensing (QS) inhibitors.ConclusionDue to the structural similarity of these compounds to each other, and to key molecules in AI‐2 biosynthetic pathways, we propose that these molecules potentially reduce biofilm formation via antagonism of QS or QS‐related pathways.Significance and Impact of the StudyThis study highlights the potential for a non‐antimicrobial‐based strategy, focused on AI‐2 cell–cell signalling, to control the development of dental plaque. Considering that many bacterial species use AI‐2 cell–cell signalling, as well as the increased concern of the use of antimicrobials in healthcare products, such an anti‐biofilm approach could also be used to control biofilms in environments beyond the human oral cavity.