Fischetti Vincent A
Laboratory of Bacterial Pathogenesis; Rockefeller University; New York, NY USA.
Bacteriophage. 2011 Jul 1;1(4):188-194. doi: 10.4161/bact.1.4.17747.
In the billion years that bacteriophage (or phage) have existed together with bacteria the phage have evolved systems that may be exploited for our benefit. One of these is the lytic system used by the phage to release their progeny from an infected bacterium. Endolysins (or lysins) are highly evolved enzymes in the lytic system produced to cleave essential bonds in the bacterial cell wall peptidoglycan for progeny release. Small quantities of purified recombinant lysin added externally to gram-positive bacteria results in immediate lysis causing log-fold death of the target bacterium. Lysins have now been used successfully in a variety of animal models to control pathogenic antibiotic resistant bacteria found on mucosal surfaces and in infected tissues. The advantages over antibiotics are their specificity for the pathogen without disturbing the normal flora, the low chance of bacterial resistance, and their ability to kill colonizing pathogens on mucosal surfaces, a capacity previously unavailable. Lysins therefore, may be a much-needed anti-infective (or enzybiotic) in an age of mounting antibiotic resistance.
在噬菌体与细菌共存的数十亿年里,噬菌体已经进化出了一些可为我们所用的系统。其中之一是噬菌体用于从受感染细菌中释放其后代的裂解系统。内溶素(或溶素)是裂解系统中高度进化的酶,其产生的目的是裂解细菌细胞壁肽聚糖中的关键化学键,以便后代释放。将少量纯化的重组溶素外部添加到革兰氏阳性细菌中会导致立即裂解,使目标细菌呈对数级死亡。溶素现已成功用于多种动物模型,以控制在粘膜表面和受感染组织中发现的致病性抗生素抗性细菌。与抗生素相比,其优势在于对病原体具有特异性,不会干扰正常菌群,细菌产生抗性的可能性低,以及能够杀死粘膜表面的定植病原体,这是以前所没有的能力。因此,在抗生素耐药性不断增加的时代,溶素可能是一种急需的抗感染剂(或酶生素)。