Titball R W
Microbiology Group, Defence Evaluation and Research Agency, Salisbury, Wilts, UK.
Symp Ser Soc Appl Microbiol. 1998;27:127S-137S.
The phospholipases are a diverse group of enzymes, produced by a variety of Gram-positive and Gram-negative bacteria. The roles of these enzymes in the pathogenesis of infectious disease is equally diverse. It is only recently that molecular genetic approaches have allowed data to be obtained which indicates the role of these enzymes in the disease process. In the case of some pathogens phospholipases play an overriding role in disease. Roles for these enzymes have been demonstrated in the pathogenesis of disease caused by extracellular and intracellular pathogens and by disease caused by pathogens which enter via the respiratory tract, the intestinal tract or after traumatic injury. Some of the mechanisms by which phospholipases C affect tissues in vitro or ex vivo are understood but, in the main, the mechanisms by which phospholipases C affect tissues in vivo are not known. A key event, which can determine the extent of involvement of phospholipases in the disease process, is the interaction of the enzyme with phospholipids in eukaryotic cell membranes. Whilst progress has been made in understanding the molecular basis of these interactions, the process is far from understood. Two theories attempt to explain the reasons why only some phospholipases C are membrane active. In general, the membrane active enzymes are able to hydrolyse both phosphatidylcholine and sphingomyelin and appear to have mechanisms which allow them to interact with membrane phospholipids. The structural differences between phosphatidylcholine and sphingomyelin lie within the fatty acyl chain/ester bond region which would be partially embedded in the membrane bilayer. Therefore, there may be a common explanation for membrane interaction and recognition of both phospholipid types. The value of this information will be several fold. The demonstration of the role of these enzymes in disease will allow the development of vaccines or therapeutics which block the effects of these enzymes. In this context it is worth bearing in mind that eukaryotic phospholipases C, which play key roles in many inflammatory and autoimmune diseases, are the subject of intense study by the pharmaceutical industry. Some of the bacterial toxins are potent cytotoxic agents and this has encouraged some workers to explore the possibility that immunotoxins can be developed (Chovnick et al. 1991). Purified recombinant phospholipases C will continue to be used in the study of cell membranes, and the increasing numbers of enzymes with different substrate specificities will enhance their application.
磷脂酶是一类多样的酶，由多种革兰氏阳性菌和革兰氏阴性菌产生。这些酶在传染病发病机制中的作用同样多样。直到最近，分子遗传学方法才使人们获得了表明这些酶在疾病过程中作用的数据。对于某些病原体而言，磷脂酶在疾病中起着至关重要的作用。这些酶在由细胞外和细胞内病原体引起的疾病以及由经呼吸道、肠道或外伤后进入人体的病原体引起的疾病的发病机制中都发挥了作用。磷脂酶C在体外或离体条件下影响组织的一些机制已为人所知，但总体而言，磷脂酶C在体内影响组织的机制尚不清楚。一个能决定磷脂酶参与疾病过程程度的关键事件是该酶与真核细胞膜中的磷脂相互作用。虽然在理解这些相互作用的分子基础方面已取得进展，但这个过程仍远未被完全理解。有两种理论试图解释为什么只有一些磷脂酶C具有膜活性。一般来说，具有膜活性的酶能够水解磷脂酰胆碱和鞘磷脂，并且似乎具有使其能够与膜磷脂相互作用的机制。磷脂酰胆碱和鞘磷脂之间的结构差异存在于脂肪酸酰基链/酯键区域，该区域会部分嵌入膜双层中。因此，对于膜相互作用以及对这两种磷脂类型的识别可能存在一个共同的解释。这些信息的价值体现在多个方面。证明这些酶在疾病中的作用将有助于开发能阻断这些酶作用的疫苗或治疗方法。在这种情况下，值得记住的是，在许多炎症和自身免疫性疾病中起关键作用的真核磷脂酶C是制药行业深入研究的对象。一些细菌毒素是强效细胞毒性剂，这促使一些研究人员探索开发免疫毒素的可能性（乔夫尼克等人，1991年）。纯化的重组磷脂酶C将继续用于细胞膜的研究，并且越来越多具有不同底物特异性的酶将增强它们的应用。
