Jack R W, Tagg J R, Ray B
Russell Grimwade School of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
Microbiol Rev. 1995 Jun;59(2):171-200. doi: 10.1128/mr.59.2.171-200.1995.
In recent years, a group of antibacterial proteins produced by gram-positive bacteria have attracted great interest in their potential use as food preservatives and as antibacterial agents to combat certain infections due to gram-positive pathogenic bacteria. They are ribosomally synthesized peptides of 30 to less than 60 amino acids, with a narrow to wide antibacterial spectrum against gram-positive bacteria; the antibacterial property is heat stable, and a producer strain displays a degree of specific self-protection against its own antibacterial peptide. In many respects, these proteins are quite different from the colicins and other bacteriocins produced by gram-negative bacteria, yet customarily they also are grouped as bacteriocins. Although a large number of these bacteriocins (or bacteriocin-like inhibitory substances) have been reported, only a few have been studied in detail for their mode of action, amino acid sequence, genetic characteristics, and biosynthesis mechanisms. Nevertheless, in general, they appear to be translated as inactive prepeptides containing an N-terminal leader sequence and a C-terminal propeptide component. During posttranslational modifications, the leader peptide is removed. In addition, depending on the particular type, some amino acids in the propeptide components may undergo either dehydration and thioether ring formation to produce lanthionine and beta-methyl lanthionine (as in lantibiotics) or thio ester ring formation to form cystine (as in thiolbiotics). Some of these steps, as well as the translocation of the molecules through the cytoplasmic membrane and producer self-protection against the homologous bacteriocin, are mediated through specific proteins (enzymes). Limited genetic studies have shown that the structural gene for such a bacteriocin and the genes encoding proteins associated with immunity, translocation, and processing are present in a cluster in either a plasmid, the chromosome, or a transposon. Following posttranslational modification and depending on the pH, the molecules may either be released into the environment or remain bound to the cell wall. The antibacterial action against a sensitive cell of a gram-positive strain is produced principally by destabilization of membrane functions. Under certain conditions, gram-negative bacterial cells can also be sensitive to some of these molecules. By application of site-specific mutagenesis, bacteriocin variants which may differ in their antimicrobial spectrum and physicochemical characteristics can be produced. Research activity in this field has grown remarkably but sometimes with an undisciplined regard for conformity in the definition, naming, and categorization of these molecules and their genetic effectors. Some suggestions for improved standardization of nomenclature are offered.
近年来,革兰氏阳性菌产生的一类抗菌蛋白引起了人们极大的兴趣,因为它们有可能用作食品防腐剂以及作为抗菌剂来对抗某些由革兰氏阳性病原菌引起的感染。它们是核糖体合成的肽,由30至少于60个氨基酸组成,对革兰氏阳性菌具有窄到宽的抗菌谱;抗菌特性对热稳定,并且产生菌对其自身的抗菌肽具有一定程度的特异性自我保护。在许多方面,这些蛋白质与革兰氏阴性菌产生的大肠杆菌素和其他细菌素截然不同,但习惯上它们也被归类为细菌素。尽管已经报道了大量的这些细菌素(或类细菌素抑制物质),但只有少数几种在作用方式、氨基酸序列、遗传特性和生物合成机制方面得到了详细研究。然而,一般来说,它们似乎被翻译为含有N端前导序列和C端前肽成分的无活性前肽。在翻译后修饰过程中,前导肽被去除。此外,根据具体类型,前肽成分中的一些氨基酸可能会经历脱水和硫醚环形成以产生羊毛硫氨酸和β-甲基羊毛硫氨酸(如在羊毛硫抗生素中)或硫酯环形成以形成胱氨酸(如在硫醇类抗生素中)。这些步骤中的一些,以及分子通过细胞质膜的转运和产生菌对同源细菌素的自我保护,是由特定蛋白质(酶)介导的。有限的遗传学研究表明,这种细菌素的结构基因以及编码与免疫、转运和加工相关蛋白质的基因存在于质粒、染色体或转座子中的一个簇中。翻译后修饰后,根据pH值,分子可能会释放到环境中或仍然与细胞壁结合。对革兰氏阳性菌株敏感细胞的抗菌作用主要是通过膜功能的不稳定产生的。在某些条件下,革兰氏阴性细菌细胞也可能对其中一些分子敏感。通过应用位点特异性诱变,可以产生在抗菌谱和物理化学特性上可能不同的细菌素变体。该领域的研究活动显著增加,但有时对这些分子及其遗传效应物的定义、命名和分类缺乏统一规范。本文提出了一些改进命名标准化的建议。