Identification of signaling pathways, matrix-digestion enzymes, and motility components controlling Vibrio cholerae biofilm dispersal.
Identification of signaling pathways, matrix-digestion enzymes, and motility components controlling Vibrio cholerae biofilm dispersal.
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DOI：
10.1073/pnas.2021166117
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发表时间：
2020-12-22
影响因子：
11.1
通讯作者：
Bassler BL
中科院分区：
文献类型：
--
作者：
Bridges AA;Fei C;Bassler BL
全球病原体霍乱弧菌在自由游动和存在于被称为生物膜的固定多细胞群落之间交替。这些生活方式之间的转换是疾病传播的关键。霍乱弧菌生物膜的形成得到了很好的研究；然而，关于霍乱弧菌细胞如何从生物膜上分散几乎一无所知，这妨碍了我们对中心致病性步骤的理解。在这里，我们对未能分散的霍乱弧菌突变体进行了成像筛选。我们的筛选揭示了扩散所需的三类成分：信号转导、基质降解和运动因子。我们对这些成分进行了表征，以揭示编排霍乱弧菌生物膜扩散的分子事件序列。我们的报告为制定调节生物膜扩散以预防或治疗疾病的策略提供了一个框架。细菌在自由游动和作为被称为生物膜的固定多细胞群落的成员之间交替存在。生物膜的生命周期分为三个阶段：细胞附着、生物膜成熟和生物膜扩散。霍乱弧菌生物膜具有高传染性，生物膜的形成和扩散被认为是疾病传播的核心。虽然生物膜的形成已经得到了很好的研究，但对生物膜的扩散却几乎一无所知。在这里，我们对无法分散的霍乱弧菌突变体进行了成像筛选，揭示了三类分散成分：信号转导蛋白、基质降解酶和运动因子。信号蛋白在筛选中占主导地位，其中，我们重点研究了一个未表征的双组分感觉系统，我们将其称为DbfS/DbfR，用于生物膜传感器/调节器的分散。Phospho-DbfR抑制生物膜扩散。dbf去磷酸化，从而使DbfR失活，从而允许扩散。基质降解需要两种酶：分解粘附素的LapG酶和消化基质多糖的rmb酶。由CheY3介导的游动方向的重新定向是细胞从多孔生物膜基质中逃逸所必需的。我们认为这些成分是顺序作用的：信号通过终止基质产生和触发基质消化来启动扩散，随后的细胞运动允许从生物膜中逃逸。本研究为旨在调节霍乱弧菌生物膜扩散以改善疾病的干预奠定了基础。
The global pathogen Vibrio cholerae alternates between free swimming and existing in sessile multicellular communities known as biofilms. Transitioning between these lifestyles is key for disease transmission. V. cholerae biofilm formation is well studied; however, almost nothing is known about how V. cholerae cells disperse from biofilms, precluding our understanding of a central pathogenicity step. Here, we conducted an imaging screen for V. cholerae mutants that failed to disperse. Our screen revealed three classes of components required for dispersal: signal transduction, matrix degradation, and motility factors. We characterized these components to reveal the sequence of molecular events that choreograph V. cholerae biofilm dispersal. Our report provides a framework for developing strategies to modulate biofilm dispersal to prevent or treat disease. Bacteria alternate between being free-swimming and existing as members of sessile multicellular communities called biofilms. The biofilm lifecycle occurs in three stages: cell attachment, biofilm maturation, and biofilm dispersal. Vibrio cholerae biofilms are hyperinfectious, and biofilm formation and dispersal are considered central to disease transmission. While biofilm formation is well studied, almost nothing is known about biofilm dispersal. Here, we conducted an imaging screen for V. cholerae mutants that fail to disperse, revealing three classes of dispersal components: signal transduction proteins, matrix-degradation enzymes, and motility factors. Signaling proteins dominated the screen and among them, we focused on an uncharacterized two-component sensory system that we term DbfS/DbfR for dispersal of biofilm sensor/regulator. Phospho-DbfR represses biofilm dispersal. DbfS dephosphorylates and thereby inactivates DbfR, which permits dispersal. Matrix degradation requires two enzymes: LapG, which cleaves adhesins, and RbmB, which digests matrix polysaccharides. Reorientation in swimming direction, mediated by CheY3, is necessary for cells to escape from the porous biofilm matrix. We suggest that these components act sequentially: signaling launches dispersal by terminating matrix production and triggering matrix digestion, and subsequent cell motility permits escape from biofilms. This study lays the groundwork for interventions aimed at modulating V. cholerae biofilm dispersal to ameliorate disease.
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DOI：
10.1126/science.1222981
发表时间：
2012-07-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Berk V;Fong JC;Dempsey GT;Develioglu ON;Zhuang X;Liphardt J;Yildiz FH;Chu S
通讯作者：
Chu S
影响因子：
5.4
作者：
Conner JG;Zamorano-Sánchez D;Park JH;Sondermann H;Yildiz FH
通讯作者：
Yildiz FH
影响因子：
9.8
作者：
Bridges, Andrew A.;Bassler, Bonnie L.
通讯作者：
Bassler, Bonnie L.
影响因子：
3.4
作者：
Licata, Nicholas A.;Mohari, Bitan;Setayeshgar, Sima
通讯作者：
Setayeshgar, Sima
DOI：
10.1073/pnas.0308052101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Butler, SM;Camilli, A
通讯作者：
Camilli, A