Department of Microbiology, Harvard Medical School, Boston, United States.
UMass Chan Medical School, Worcester, United States.
Elife. 2022 May 20;11:e76392. doi: 10.7554/eLife.76392.
Penicillin and related antibiotics disrupt cell wall synthesis in bacteria causing the downstream misactivation of cell wall hydrolases called autolysins to induce cell lysis. Despite the clinical importance of this phenomenon, little is known about the factors that control autolysins and how penicillins subvert this regulation to kill cells. In the pathogen (), LytA is the major autolysin responsible for penicillin-induced bacteriolysis. We recently discovered that penicillin treatment of causes a dramatic shift in surface polymer biogenesis in which cell wall-anchored teichoic acids (WTAs) increase in abundance at the expense of lipid-linked teichoic acids (LTAs). Because LytA binds to both species of teichoic acids, this change recruits the enzyme to its substrate where it cleaves the cell wall and elicits lysis. In this report, we identify WhyD (SPD_0880) as a new factor that controls the level of WTAs in cells to prevent LytA misactivation and lysis during exponential growth . We show that WhyD is a WTA hydrolase that restricts the WTA content of the wall to areas adjacent to active peptidoglycan (PG) synthesis. Our results support a model in which the WTA tailoring activity of WhyD during exponential growth directs PG remodeling activity required for proper cell elongation in addition to preventing autolysis by LytA.
青霉素和相关抗生素会破坏细菌的细胞壁合成，导致细胞壁水解酶（称为自溶素）的下游错误激活，从而诱导细胞裂解。尽管这种现象具有重要的临床意义，但人们对控制自溶素的因素以及青霉素如何破坏这种调节以杀死细胞知之甚少。在病原体 （）中，LytA 是主要的自溶素，负责青霉素诱导的细菌溶解。我们最近发现，青霉素处理 会导致表面聚合物生物发生的剧烈转变，其中细胞壁锚定的磷壁酸（WTAs）的丰度增加，而脂质连接的磷壁酸（LTAs）则减少。由于 LytA 结合两种类型的磷壁酸，这种变化会将酶募集到其底物上，在那里它会切割细胞壁并引发裂解。在本报告中，我们确定了 WhyD（SPD_0880）作为一种新的因子，它可以控制 细胞中 WTA 的水平，以防止 LytA 在指数生长期的错误激活和裂解。我们表明，WhyD 是一种 WTA 水解酶，它将 WTA 的含量限制在与活性肽聚糖（PG）合成相邻的细胞壁区域。我们的结果支持这样一种模型，即在指数生长期，WhyD 的 WTA 修剪活性指导 PG 重塑活性，这是除了防止 LytA 自溶之外，细胞正常伸长所必需的。
