Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Pathogens. 2012 Jul 20;1(1):3-11. doi: 10.3390/pathogens1010003.
Several members of the staphylococcal phenol-soluble modulin (PSM) peptide family exhibit pronounced capacities to lyse eukaryotic cells, such as neutrophils, monocytes, and erythrocytes. This is commonly assumed to be due to the amphipathic, α-helical structure of PSMs, giving PSMs detergent-like characteristics and allowing for a relatively non-specific destruction of biological membranes. However, the capacities of PSMs to lyse synthetic phospholipid vesicles have not been investigated. Here, we analyzed lysis of synthetic phosphatidylcholine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC) vesicles by all Staphylococcus aureus and S. epidermidis PSMs. In addition, we investigated the lytic capacities of culture filtrates obtained from different S. aureus PSM deletion mutants toward POPC vesicles. Our results show that all staphylococcal PSMs have phospholipid vesicle-lysing activity and the capacity of S. aureus culture filtrate to lyse POPC vesicles is exclusively dependent on PSMs. Notably, we observed largely differing capacities among PSM peptides to lyse POPC vesicles. Interestingly, POPC vesicle-lytic capacities did not correlate with those previously seen for the lysis of eukaryotic cells. For example, the β-type PSMs were strongly lytic for POPC vesicles, but are known to exhibit only very low lytic capacities toward neutrophils and erythrocytes. Thus our results also suggest that the interaction between PSMs and eukaryotic membranes is more specific than previously assumed, potentially depending on additional structural features of those membranes, such as phospholipid composition or yet unidentified docking molecules.
葡萄球菌酚溶性调节素（PSM）肽家族的几个成员表现出明显的裂解真核细胞（如中性粒细胞、单核细胞和红细胞）的能力。这通常归因于 PSM 的两亲性、α-螺旋结构，赋予 PSM 去污剂样特性，并允许对生物膜进行相对非特异性的破坏。然而，尚未研究 PSM 裂解合成磷脂囊泡的能力。在这里，我们分析了所有金黄色葡萄球菌和表皮葡萄球菌 PSM 对合成磷脂酰胆碱（1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱，POPC）囊泡的裂解。此外，我们还研究了来自不同金黄色葡萄球菌 PSM 缺失突变体的培养滤液对 POPC 囊泡的裂解能力。我们的结果表明，所有葡萄球菌 PSM 都具有磷脂囊泡裂解活性，金黄色葡萄球菌培养滤液裂解 POPC 囊泡的能力完全依赖于 PSM。值得注意的是，我们观察到 PSM 肽裂解 POPC 囊泡的能力存在很大差异。有趣的是，POPC 囊泡裂解能力与先前观察到的真核细胞裂解能力没有相关性。例如，β 型 PSM 对 POPC 囊泡具有强烈的裂解活性，但已知对中性粒细胞和红细胞的裂解活性非常低。因此，我们的结果还表明，PSM 与真核细胞膜之间的相互作用比之前假设的更为特异，可能取决于这些膜的其他结构特征，如磷脂组成或尚未确定的对接分子。
