Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation in Listeria monocytogenes.
Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation in Listeria monocytogenes.
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DOI：
10.1021/acs.biochem.3c00373
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发表时间：
2023-10-03
期刊：
影响因子：
2.9
通讯作者：
Blackwell, Helen E.
中科院分区：
文献类型：
--
作者：
West, Korbin H. J.;Ma, Stella V.;Pensinger, Daniel A.;Tucholski, Trisha;Tiambeng, Timothy N.;Eisenbraun, Emma L.;Yehuda, Avishag;Hayouka, Zvi;Ge, Ying;Sauer, John-Demian;Blackwell, Helen E.
细菌可以利用化学信号来评估其本地种群密度，这一过程被称为群体感应（QS）。这些细菌中有许多是常见的病原体，包括革兰氏阳性细菌，它们利用由大环自诱导肽（AIP）信号调节的agr QS系统。单核增生李斯特菌是一种重要的食源性病原体，它通过agr系统调节多种毒力因子和生物膜的形成，但对agr在李斯特菌感染及其在各种环境中的持续存在中的具体作用知之甚少。在此，我们报告了合成肽工具，将使研究QS在李斯特菌。我们在单核增生乳杆菌上清液中鉴定了一个6聚AIP信号，并选择它作为支架，围绕它设计和合成一系列非原生AIP模拟物。这些肽在基于细胞的agr报告细胞实验中被评估，以产生单核细胞增生L.基于aip的激动作用和拮抗作用的结构-活性关系。我们发现合成激动剂相对于天然AIP具有更高的效力，合成拮抗剂能够将agr活性降低到基础水平。值得注意的是，后一种肽能够减少90%以上的生物膜形成，这是野生型单核增生乳杆菌中首次合成QS调节剂。单核增生乳杆菌中的先导agr激动剂和拮抗剂也能拮抗相关病原菌金黄色葡萄球菌中的agr信号，进一步扩展了它们的用途，并提示了这两种病原菌中agr激活的不同机制。本研究是应用化学方法调控单增李斯特菌QS及其毒力结果的重要的第一步。
Bacteria can use chemical signals to assess their local population density in a process called quorum sensing (QS). Many of these bacteria are common pathogens, including Gram-positive bacteria that utilize agr QS systems regulated by macrocyclic autoinducing peptide (AIP) signals. Listeria monocytogenes, an important food-borne pathogen, uses an agr system to regulate a variety of virulence factors and biofilm formation, yet little is known about the specific roles of agr in Listeria infection and its persistence in various environments. Herein, we report synthetic peptide tools that will enable study of QS in Listeria. We identified a 6-mer AIP signal in L. monocytogenes supernatants and selected it as a scaffold around which to design and synthesize a collection of non-native AIP mimics. These peptides were evaluated in cell-based agr reporter assays to generate structure-activity relationships for AIP-based agonism and antagonism in L. monocytogenes. We discovered synthetic agonists with increased potency relative to the native AIP and a synthetic antagonist capable of reducing agr activity to basal levels. Notably, the latter peptide was able to reduce biofilm formation by over 90%, a first for a synthetic QS modulator in wild-type L. monocytogenes. The lead agr agonist and antagonist in L. monocytogenes were also capable of antagonizing agr signaling in the related pathogen Staphylococcus aureus, further extending their utility and suggesting different mechanisms of agr activation in these two pathogens. This study represents an important first step in the application of chemical methods to modulate QS and concomitant virulence outcomes in L. monocytogenes.
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影响因子：
4
作者：
Bikash CR;Tal-Gan Y
通讯作者：
Tal-Gan Y
影响因子：
3.1
作者：
Autret, N;Raynaud, C;Charbit, A
通讯作者：
Charbit, A
DOI：
10.3390/s130405130
发表时间：
2013-04-18
期刊：
Sensors (Basel, Switzerland)
影响因子：
--
作者：
Gray B;Hall P;Gresham H
通讯作者：
Gresham H
增加AIP大环的大小揭示了金黄色葡萄球菌中AGR激活的关键特征。
DOI：
10.1002/cbic.201500006
发表时间：
2015-05-04
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Johnson JG;Wang B;Debelouchina GT;Novick RP;Muir TW
通讯作者：
Muir TW
影响因子：
3.7
作者：
Garmyn, Dominique;Augagneur, Yoann;Piveteau, Pascal
通讯作者：
Piveteau, Pascal