The WaIR-WalK Signaling Pathway Modulates the Activities o both CwlO and LytE through Control of the Peptidoglycan Deacetylase PdaC in Bacillus subtilis
The WaIR-WalK Signaling Pathway Modulates the Activities o both CwlO and LytE through Control of the Peptidoglycan Deacetylase PdaC in Bacillus subtilis
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DOI：
10.1128/jb.00533-21
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发表时间：
2022-02-01
影响因子：
3.2
通讯作者：
Rudner, David Z.
中科院分区：
文献类型：
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作者：
Dobihal, Genevieve S.;Flores-Kim, Josue;Rudner, David Z.
枯草芽孢杆菌中的 WaIR-WalK 两组分信号系统在细胞生长所需的肽聚糖 (PG) 水解酶 LytE 和 CwlO 的稳态控制中发挥作用。当这些酶的活性较低时，WaIR 会激活 lytE 和 CwlO 的转录，并抑制 iseA（LytE 的分泌型抑制剂）的转录。相反，当PG水解酶活性过高时，lytE和CwlO的WaIR依赖性表达会减少，并且iseA会被去抑制。在筛选调节该信号通路的其他因素时，我们发现膜锚定的 PG 脱乙酰酶 PdaC 的过度表达会增加 WaIR 依赖性基因的表达。我们发现，PdaC 表达的增加（而非催化突变体）阻止了 LytE 和 CwlO 对细胞壁的裂解，这解释了 WaIR 的激活。重要的是，pdaC 基因与 iseA 一样，受到活性 WaIR 的抑制。我们认为，当 PG 水解酶活性过高时，pdaC 的去抑制会导致 PG 近膜层的修饰，从而保护壁免受膜束缚的 CwlO 的过度裂解。因此，WaIR-WalK 系统稳态控制两种伸长特异性细胞壁水解酶的水平和活性。 重要性 细菌生长和分裂需要细胞壁外骨骼的合成和重塑之间的微妙平衡。细菌如何调节重塑细胞壁肽聚糖的潜在自溶酶仍不完全清楚。在这里，我们提供的证据表明，广泛保守的 WaIR-WalK 双组分信号系统能够稳态控制对细胞生长至关重要的两种细胞壁水解酶的水平和活性。
The WaIR-WalK two component signaling system in Bacillus subtilis functions in the homeostatic control of the peptidoglycan (PG) hydrolases LytE and CwlO that are required for cell growth. When the activities of these enzymes are low, WaIR activates transcription of lytE and CwlO and represses transcription of iseA, a secreted inhibitor of LytE. Conversely, when PG hydrolase activity is too high, WaIR-dependent expression of lytE and CwlO is reduced and iseA is derepressed. In a screen for additional factors that regulate this signaling pathway, we discovered that overexpression of the membrane-anchored PG deacetylase PdaC increases WaIR-dependent gene expression. We show that increased expression of PdaC, but not catalytic mutants, prevents cell wall cleavage by both LytE and CwlO, explaining the WaIR activation. Importantly, the pdaC gene, like iseA, is repressed by active WaIR. We propose that derepression of pdaC when PG hydrolase activity is too high results in modification of the membrane-proximal layers of the PG, protecting the wall from excessive cleavage by the membrane-tethered CwlO. Thus, the WaIR-WalK system homeostatically controls the levels and activities of both elongation-specific cell wall hydrolases.IMPORTANCE Bacterial growth and division requires a delicate balance between the synthesis and remodeling of the cell wall exoskeleton. How bacteria regulate the potentially autolytic enzymes that remodel the cell wall peptidoglycan remains incompletely understood. Here, we provide evidence that the broadly conserved WaIR-WalK two-component signaling system homeostatically controls both the levels and activities of two cell wall hydrolases that are critical for cell growth.