Biofilm development on Caenorhabditis elegans by Yersinia is facilitated by quorum sensing-dependent repression of type III secretion.
Biofilm development on Caenorhabditis elegans by Yersinia is facilitated by quorum sensing-dependent repression of type III secretion.
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DOI：
10.1371/journal.ppat.1001250
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发表时间：
2011-01-06
期刊：
影响因子：
6.7
通讯作者：
Williams P
中科院分区：
文献类型：
--
作者：
Atkinson S;Goldstone RJ;Joshua GW;Chang CY;Patrick HL;Cámara M;Wren BW;Williams P
假结核耶尔森菌在秀丽隐杆线虫上形成生物膜，阻止线虫进食。这种遗传上顺从的宿主-病原体模型对于生物膜在活的、活动的表面上的发育具有重要意义。在这里，我们表明，秀丽隐杆线虫上的假结核杆菌生物膜发育受N-酰基高丝氨酸内酯（AHL）介导的群体感应（QS）控制，因为（i）AHL是在线虫相关生物膜中产生的，并且（ii）表达AHL降解酶或其中AHL合酶的假结核杆菌菌株 （ypsI 和 ytbI）或反应调节因子（ypsR 和 ytbR）基因已发生突变、减弱。尽管在 QS 控制的运动调节基因 flhDC 和 fliA 以及鞭毛蛋白输出基因 flhA 中携带突变的假结核杆菌菌株中，生物膜形成也减弱，但由于 fliC 突变体形成正常生物膜，因此不需要鞭毛。然而，与亲本和fliC突变体相反，Yop病毒蛋白在flhDC、fliA和flhA突变体中以不依赖于温度和钙的方式上调。对于假结核杆菌 QS 突变体也发现了类似的观察结果，表明 Yop 病毒通过主运动调节因子 flhDC 被 QS 抑制。通过从 ypsI/ytbI 突变体中消除 pYV 毒力质粒，通过在允许 III 型针形成但不允许 Yop 分泌的条件下生长 YpIII，以及通过突变 III 型分泌装置基因 yscJ，我们表明可以在 flhDC 和 ypsI/ytbI 突变体中恢复生物膜形成。这些数据表明，III 型分泌阻断生物膜形成，并通过 QS 与运动性相互调节。许多革兰氏阴性细菌通过产生和感知化学信号分子（例如 N-酰基高丝氨酸内酯 (AHL)）的存在来进行交流。细菌细胞使用 AHL 来传达有关其环境、新陈代谢和种群规模的信息。这种类型的化学信号被称为“群体感应”（QS），通常被病原菌用来通过控制运动、毒素、组织降解酶和表面相关生物膜来促进急性或慢性感染。假结核耶尔森氏菌是一种人类病原体，在线虫秀丽隐杆线虫表面形成生物膜。这为研究活体组织上生物膜的形成提供了一种简单的方法，并且可用于识别导致生物膜相关感染的病原体和宿主的遗传特征。我们发现，群体感应是线虫上假结核杆菌生物膜形成所必需的，通过一条调控途径，该途径涉及相互控制细菌游动的主运动调节蛋白（FlhDC）和构建一种专门的分泌针，将蛋白质输送到哺乳动物细胞中以破坏其正常活动。
Yersinia pseudotuberculosis forms biofilms on Caenorhabditis elegans which block nematode feeding. This genetically amenable host-pathogen model has important implications for biofilm development on living, motile surfaces. Here we show that Y. pseudotuberculosis biofilm development on C. elegans is governed by N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) since (i) AHLs are produced in nematode associated biofilms and (ii) Y. pseudotuberculosis strains expressing an AHL-degrading enzyme or in which the AHL synthase (ypsI and ytbI) or response regulator (ypsR and ytbR) genes have been mutated, are attenuated. Although biofilm formation is also attenuated in Y. pseudotuberculosis strains carrying mutations in the QS-controlled motility regulator genes, flhDC and fliA, and the flagellin export gene, flhA, flagella are not required since fliC mutants form normal biofilms. However, in contrast to the parent and fliC mutant, Yop virulon proteins are up-regulated in flhDC, fliA and flhA mutants in a temperature and calcium independent manner. Similar observations were found for the Y. pseudotuberculosis QS mutants, indicating that the Yop virulon is repressed by QS via the master motility regulator, flhDC. By curing the pYV virulence plasmid from the ypsI/ytbI mutant, by growing YpIII under conditions permissive for type III needle formation but not Yop secretion and by mutating the type III secretion apparatus gene, yscJ, we show that biofilm formation can be restored in flhDC and ypsI/ytbI mutants. These data demonstrate that type III secretion blocks biofilm formation and is reciprocally regulated with motility via QS. Many Gram-negative bacteria communicate by producing and sensing the presence of chemical signal molecules such as the N-acylhomoserine lactones (AHLs). Bacterial cells use AHLs to convey information about their environment, metabolism and population size. This type of chemical signalling is called ‘quorum sensing’ (QS) and is often used by pathogenic bacteria to promote acute or chronic infections through the control of motility, toxins, tissue degrading enzymes and surface-associated biofilms. Yersinia pseudotuberculosis is a human pathogen which forms biofilms on the surface of the nematode worm, Caenorhabditis elegans. This offers a simple means for investigating biofilm development on living tissues and can be used to identify genetic features of both the pathogen and the host that contribute to biofilm-associated infections. We have discovered that quorum sensing is required for Y. pseudotuberculosis biofilm formation on C. elegans through a regulatory pathway which involves the master motility regulator protein (FlhDC) reciprocally controlling bacterial swimming and the construction of a specialized secretion needle that delivers proteins into mammalian cells to disrupt their normal activities.
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