Department of Microbiology, Harvard Medical School, Boston, United States.
The Florey Institute, Molecular Biology Biotechnology, University of Sheffield, Sheffield, United Kingdom.
Elife. 2019 Apr 9;8:e44912. doi: 10.7554/eLife.44912.
Penicillin and related antibiotics disrupt cell wall synthesis to induce bacteriolysis. Lysis in response to these drugs requires the activity of cell wall hydrolases called autolysins, but how penicillins misactivate these deadly enzymes has long remained unclear. Here, we show that alterations in surface polymers called teichoic acids (TAs) play a key role in penicillin-induced lysis of the Gram-positive pathogen (). We find that during exponential growth, cells primarily produce lipid-anchored TAs called lipoteichoic acids (LTAs) that bind and sequester the major autolysin LytA. However, penicillin-treatment or prolonged stationary phase growth triggers the degradation of a key LTA synthase, causing a switch to the production of wall-anchored TAs (WTAs). This change allows LytA to associate with and degrade its cell wall substrate, thus promoting osmotic lysis. Similar changes in surface polymer assembly may underlie the mechanism of antibiotic- and/or growth phase-induced lysis for other important Gram-positive pathogens.
青霉素和相关抗生素会破坏细胞壁合成，从而诱导细菌裂解。这些药物引发的裂解需要细胞壁水解酶（称为自溶酶）的活性，但青霉素如何错误地激活这些致命的酶一直不清楚。在这里，我们表明，称为磷壁酸（TAs）的表面聚合物的改变在青霉素诱导的革兰氏阳性病原体（）裂解中起着关键作用。我们发现，在指数生长期，细胞主要产生脂质锚定的磷壁酸（LTAs），这些磷壁酸结合并隔离主要的自溶酶 LytA。然而，青霉素处理或长时间的静止期生长会触发关键的 LTAs 合成酶的降解，导致产生壁锚定的 TAs（WTAs）。这种变化使得 LytA 能够与细胞壁底物结合并降解，从而促进渗透裂解。其他重要的革兰氏阳性病原体的抗生素和/或生长阶段诱导裂解的机制可能基于类似的表面聚合物组装变化。
