Francius Grégory, Domenech Oscar, Mingeot-Leclercq Marie Paule, Dufrêne Yves F
Unité de Chimie des Interfaces, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
J Bacteriol. 2008 Dec;190(24):7904-9. doi: 10.1128/JB.01116-08. Epub 2008 Oct 3.
The advent of Staphylococcus aureus strains that are resistant to virtually all antibiotics has increased the need for new antistaphylococcal agents. An example of such a potential therapeutic is lysostaphin, an enzyme that specifically cleaves the S. aureus peptidoglycan, thereby lysing the bacteria. Here we tracked over time the structural and physical dynamics of single S. aureus cells exposed to lysostaphin, using atomic force microscopy. Topographic images of native cells revealed a smooth surface morphology decorated with concentric rings attributed to newly formed peptidoglycan. Time-lapse images collected following addition of lysostaphin revealed major structural changes in the form of cell swelling, splitting of the septum, and creation of nanoscale perforations. Notably, treatment of the cells with lysostaphin was also found to decrease the bacterial spring constant and the cell wall stiffness, demonstrating that structural changes were correlated with major differences in cell wall nanomechanical properties. We interpret these modifications as resulting from the digestion of peptidoglycan by lysostaphin, eventually leading to the formation of osmotically fragile cells. This study provides new insight into the lytic activity of lysostaphin and offers promising prospects for the study of new antistaphylococcal agents.
几乎对所有抗生素均耐药的金黄色葡萄球菌菌株的出现，增加了对新型抗葡萄球菌药物的需求。这种潜在治疗药物的一个例子是溶葡萄球菌酶，一种能特异性切割金黄色葡萄球菌肽聚糖从而裂解细菌的酶。在此，我们使用原子力显微镜，长期追踪了暴露于溶葡萄球菌酶的单个金黄色葡萄球菌细胞的结构和物理动态变化。天然细胞的形貌图像显示其表面形态光滑，有归因于新形成肽聚糖的同心环。添加溶葡萄球菌酶后收集的延时图像显示出细胞肿胀、隔膜分裂以及纳米级穿孔形成等主要结构变化。值得注意的是，还发现用溶葡萄球菌酶处理细胞会降低细菌的弹簧常数和细胞壁硬度，这表明结构变化与细胞壁纳米力学性质的重大差异相关。我们将这些修饰解释为溶葡萄球菌酶对肽聚糖的消化所致，最终导致形成对渗透压敏感的脆弱细胞。这项研究为溶葡萄球菌酶的裂解活性提供了新的见解，并为新型抗葡萄球菌药物的研究提供了广阔前景。
