Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland.
Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
Nat Microbiol. 2023 Mar;8(3):387-399. doi: 10.1038/s41564-022-01317-3. Epub 2023 Jan 30.
At the end of a lytic bacteriophage replication cycle in Gram-positive bacteria, peptidoglycan-degrading endolysins that cause explosive cell lysis of the host can also attack non-infected bystander cells. Here we show that in osmotically stabilized environments, Listeria monocytogenes can evade phage predation by transient conversion to a cell wall-deficient L-form state. This L-form escape is triggered by endolysins disintegrating the cell wall from without, leading to turgor-driven extrusion of wall-deficient, yet viable L-form cells. Remarkably, in the absence of phage predation, we show that L-forms can quickly revert to the walled state. These findings suggest that L-form conversion represents a population-level persistence mechanism to evade complete eradication by phage attack. Importantly, we also demonstrate phage-mediated L-form switching of the urinary tract pathogen Enterococcus faecalis in human urine, which underscores that this escape route may be widespread and has important implications for phage- and endolysin-based therapeutic interventions.
在革兰氏阳性菌的裂解噬菌体复制周期结束时，可导致宿主细胞爆炸裂解的肽聚糖降解内溶素也可以攻击未感染的旁观者细胞。在这里，我们表明在渗透压稳定的环境中，李斯特菌可以通过短暂转化为细胞壁缺陷的 L 型状态来逃避噬菌体的捕食。这种 L 型逃避是由从外部破坏细胞壁的内溶素触发的，导致充满膨胀压的、缺乏细胞壁但仍有活力的 L 型细胞被挤出。值得注意的是，在没有噬菌体捕食的情况下，我们表明 L 型可以快速恢复到有壁状态。这些发现表明，L 型转换代表了一种群体水平的持久性机制，可以逃避噬菌体攻击的完全根除。重要的是，我们还证明了噬菌体介导的人类尿液中尿路病原体粪肠球菌的 L 型转换，这突出表明这种逃避途径可能很普遍，并对基于噬菌体和内溶素的治疗干预具有重要意义。
