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.
磷脂酶是一组不同的酶,由多种革兰氏阳性和革兰氏阴性细菌产生。这些酶在传染病发病机制中的作用同样多种多样。直到最近,分子遗传学方法才允许获得数据,表明这些酶在疾病过程中的作用。在某些病原体中,磷脂酶在疾病中起着重要作用。这些酶的作用已被证明在细胞外和细胞内病原体引起的疾病的发病机制中,以及由病原体通过呼吸道、肠道或创伤性损伤引起的疾病的发病机制中。磷脂酶C在体外或离体作用于组织的一些机制已被了解,但总的来说,磷脂酶C在体内作用于组织的机制尚不清楚。一个关键事件,可以确定磷脂酶在疾病过程中的参与程度,是酶与真核细胞膜磷脂的相互作用。虽然在了解这些相互作用的分子基础方面取得了进展,但对其过程的了解还远远不够。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,膜活性酶能够水解磷脂酰胆碱和鞘磷脂,并且似乎具有允许它们与膜磷脂相互作用的机制。磷脂酰胆碱与鞘磷脂的结构差异在于脂肪酰基链/酯键区域,该区域部分嵌入膜双分子层。因此,对于两种磷脂类型的膜相互作用和识别可能有一个共同的解释。这一信息的价值将是几倍。证明这些酶在疾病中的作用将有助于开发阻断这些酶作用的疫苗或疗法。在这种情况下,值得记住的是,真核磷脂酶C在许多炎症和自身免疫性疾病中起着关键作用,是制药工业加紧研究的主题。有些细菌毒素是强效的细胞毒素,这促使一些工人探索开发免疫毒素的可能性(Chovnick et al. 1991)。纯化的重组磷脂酶C将继续用于细胞膜的研究,不同底物特异性酶数量的增加将增强其应用。
{"title":"Bacterial phospholipases.","authors":"R W Titball","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":79733,"journal":{"name":"Symposium series (Society for Applied Microbiology)","volume":"27 ","pages":"127S-137S"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20665178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}