Activation of ChvG-ChvI regulon by cell wall stress confers resistance to β-lactam antibiotics and initiates surface spreading in Agrobacterium tumefaciens.
Activation of ChvG-ChvI regulon by cell wall stress confers resistance to β-lactam antibiotics and initiates surface spreading in Agrobacterium tumefaciens.
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DOI：
10.1371/journal.pgen.1010274
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发表时间：
2022-12
期刊：
影响因子：
4.5
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中科院分区：
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作为几乎所有细菌的核心成分，细胞壁是广谱抗生素的理想靶标。许多细菌已经进化出了感知和响应抗生素的策略，这些抗生素靶向细胞壁的合成，特别是在土壤中，产生抗生素的细菌相互竞争。在这里，我们表明，细胞壁压力所造成的化学和遗传抑制的必要的，双功能的青霉素结合蛋白PBP 1a防止微菌落形成和激活典型的主机入侵双组分系统ChvG-ChvI在根癌农杆菌。使用RNA-seq，我们表明，6小时的PBP 1a耗竭导致鞭毛依赖性运动基因的转录下调，VI型分泌和琥珀聚糖生物合成基因的转录上调，这是ChvG-ChvI调节子的标志。消耗PBP 1a 16小时，导致许多其他基因的差异表达，并可能促进应激反应，类似于其他细菌中的σ因子。值得注意的是，琥珀聚糖的过量产生导致细胞扩散，并且琥珀聚糖生物合成基因exoA的缺失恢复了小菌落形成。用头孢磺啶处理表型模拟PBP 1a的消耗，我们相应地发现chvG和chvI突变体对头孢磺啶过敏。这种超敏反应仅发生在对β-内酰胺类抗生素治疗的反应中，表明ChvG-ChvI途径可能在对靶向细胞壁合成的抗生素的耐药性中发挥关键作用。最后，我们提供的证据表明，ChvG-ChvI可能有一个保守的作用，赋予抗细胞壁应力内的Alphaproteobacteria是独立的ChvG-ChvI阻遏exoR。土壤中的细菌生活在不断变化的环境中，这要求它们经常适应压力条件以确保生存。细菌被膜提供结构完整性和保护以抵抗由环境施加的渗透压和膨压。虽然细胞膜和细胞壁生物发生的机制已被广泛研究，但我们对不同微生物如何响应细胞包膜和细胞壁压力以增加其适应性的理解仍然有限。在这项工作中，我们确定ChvG-ChvI调节子作为一个信封应力响应系统，赋予保护下的细胞壁应力条件下的细菌性植物病原体根癌农杆菌。这是一个新的功能，充分表征的ChvG-ChvI途径，也是酸诱导和促进植物宿主入侵。我们的研究结果表明，ChvG-ChvI途径在保护Alphaproteobacterial细胞免受细胞外胁迫方面具有广泛的保守作用，在响应酸胁迫和促进植物-微生物相互作用方面具有更具体的作用。
A core component of nearly all bacteria, the cell wall is an ideal target for broad spectrum antibiotics. Many bacteria have evolved strategies to sense and respond to antibiotics targeting cell wall synthesis, especially in the soil where antibiotic-producing bacteria compete with one another. Here we show that cell wall stress caused by both chemical and genetic inhibition of the essential, bifunctional penicillin-binding protein PBP1a prevents microcolony formation and activates the canonical host-invasion two-component system ChvG-ChvI in Agrobacterium tumefaciens. Using RNA-seq, we show that depletion of PBP1a for 6 hours results in a downregulation in transcription of flagellum-dependent motility genes and an upregulation in transcription of type VI secretion and succinoglycan biosynthesis genes, a hallmark of the ChvG-ChvI regulon. Depletion of PBP1a for 16 hours, results in differential expression of many additional genes and may promote a stress response, resembling those of sigma factors in other bacteria. Remarkably, the overproduction of succinoglycan causes cell spreading and deletion of the succinoglycan biosynthesis gene exoA restores microcolony formation. Treatment with cefsulodin phenocopies depletion of PBP1a and we correspondingly find that chvG and chvI mutants are hypersensitive to cefsulodin. This hypersensitivity only occurs in response to treatment with β-lactam antibiotics, suggesting that the ChvG-ChvI pathway may play a key role in resistance to antibiotics targeting cell wall synthesis. Finally, we provide evidence that ChvG-ChvI likely has a conserved role in conferring resistance to cell wall stress within the Alphaproteobacteria that is independent of the ChvG-ChvI repressor ExoR. Soil dwelling bacteria reside in changing environments requiring them to frequently adapt to stressful conditions to ensure survival. The bacterial envelope provides structural integrity and protection against osmotic stress and turgor pressure imposed by the environment. While the mechanisms of cell membrane and cell wall biogenesis have been extensively studied, our understanding of how diverse microbes respond to cell envelope and cell wall stress to increase their fitness remains limited. In this work, we identify ChvG-ChvI regulon as an envelope stress response system that confers protection under cell wall stress conditions in the bacterial plant pathogen Agrobacterium tumefaciens. This is a new function for the well-characterized ChvG-ChvI pathway which is also acid induced and promotes plant host invasion. Our results suggest that the ChvG-ChvI pathway has a broadly conserved role in protecting Alphaproteobacterial cells from extracellular stress and a more specific role in response to acid stress and promoting plant-microbe interactions.
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