Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme
Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme
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DOI：
10.1073/pnas.061038398
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发表时间：
2001-03-27
影响因子：
11.1
通讯作者：
Fischetti, VA
中科院分区：
文献类型：
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作者：
Nelson, D;Loomis, L;Fischetti, VA
噬菌体裂解酶迅速破坏宿主细菌的细胞壁，释放出后代噬菌体。由于这种裂解酶能特异性地杀死生产它们的物种，它们可能是一种在不干扰正常微生物区系的情况下控制病原菌的有效方法。在这份报告中，我们研究了一种来自链球菌噬菌体C-1的毛脲水解酶，称为赖氨酸。这种酶是A、C和E组链球菌所特有的，对几种口腔链球菌或其他共生生物几乎没有或几乎没有活性。在体外使用纯化的溶酶，我们发现1,000单位(10 Ng)的酶足以在5秒内杀灭大约10(7)群A组链球菌。当首先向小鼠口腔中加入单剂溶素(250单位)，然后加入10(7)活的A组链球菌，与没有溶素的对照组(70.5%感染，n=17)相比，它提供了防止定植的保护(28.5%感染，n=21)(P<；0.03)。此外，当给9只重定植小鼠口服500单位的溶菌素时，2小时后未发现可检出的链球菌。总之，这些研究表明，溶素是一种独特的毛霉素水解酶，在体外和体内都能对A组链球菌产生快速致死作用，而不会影响所分析的其他本土微生物。这一一般方法可用于消除或减少携带者或感染者上呼吸道粘膜上皮中的链球菌，从而减少相关疾病。
Bacteriophage lytic enzymes quickly destroy the cell wall of the host bacterium to release progeny phage. Because such lytic enzymes specifically kill the species in which they were produced, they may represent an effective way to control pathogenic bacteria without disturbing normal microflora. In this report, we studied a murein hydrolase from the streptococcal bacteriophage C-1 termed lysin. This enzyme is specific for groups A, C, and E streptococci, with little or no activity toward several oral streptococci or other commensal organisms tested. Using purified lysin in vitro, we shaw that 1,000 units (10 ng) of enzyme is sufficient to sterilize a culture of approximate to 10(7) group A streptococci within 5 seconds. When a single dose of lysin (250 units) is first added to the oral cavity of mice, followed by 10(7) live group A streptococci, it provides protection from colonization (28.5% infected, n = 21) compared with controls without lysin (70.5% infected, n = 17) (P < 0.03). Furthermore, when lysin (500 units) was given orally to 9 heavily colonized mice, no detectable streptococci were observed 2 h after lysin treatment. In all, these studies show that lysin represents a unique murein hydrolase that has a rapid lethal effect both in vitro and in vivo on group A streptococci, without affecting other indigenous microorganisms analyzed. This general approach may be used to either eliminate or reduce streptococci from the upper respiratory mucosal epithelium of either carriers or infected individuals, thus reducing associated disease.