May A K, Gleason T G, Sawyer R G, Pruett T L
Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville, Virginia.
Infect Immun. 2000 Jan;68(1):176-83. doi: 10.1128/IAI.68.1.176-183.2000.
Alpha-hemolysin (Hly) is a common exotoxin produced by Escherichia coli that enhances virulence in a number of clinical infections. The addition of hemolysin production to laboratory bacterial strains is known to increase the lethality of E. coli peritonitis. However, the mechanisms involved have not been determined and the contribution of hemolysin to the alterations in the host intraperitoneal environment and the leukocyte response is not known. Utilizing a rat peritonitis model, we show that wild-type hemolytic E. coli strains have a significant competitive advantage over nonhemolytic strains within the peritoneum. To examine the specific contribution of Hly to E. coli-induced virulence and alterations within the peritoneum, a mixed peritonitis model of E. coli, Bacteroides fragilis, and sterile fecal adjuvant was used. Three transformed E. coli strains were utilized: one strongly secretes active hemolysin (WAF 270), a second secretes active hemolysin but a reduced amount (WAF 260), and the third does not produce hemolysin (WAF 108). After an equal inoculum of each of the three strains, WAF 270 produced a markedly increased lethality and an increased recovery of both E. coli and B. fragilis from the host relative to the other strains. Changes in the intraperitoneal pH, degree of erythrocyte lysis, and recruitment and viability of leukocytes within the peritoneum following the induction of peritonitis differed significantly between the strongly hemolytic and nonhemolytic strains. Induction of peritonitis with WAF 270 caused a pronounced decrease in intraperitoneal pH, lysis of most of the intraperitoneal erythrocytes, and a marked decrease in recoverable viable leukocytes compared to WAF 108. Thus, hemolysin production by E. coli within the peritoneum may alter not only the host's ability to control the hemolytic strain itself but also other organisms.
α-溶血素(Hly)是大肠杆菌产生的一种常见外毒素,它在许多临床感染中增强毒力。已知向实验室细菌菌株中添加溶血素的产生会增加大肠杆菌腹膜炎的致死率。然而,其中涉及的机制尚未确定,溶血素对宿主腹腔内环境变化和白细胞反应的作用尚不清楚。利用大鼠腹膜炎模型,我们发现野生型溶血性大肠杆菌菌株在腹腔内比非溶血性菌株具有显著的竞争优势。为了研究Hly对大肠杆菌诱导的毒力和腹腔内变化的具体作用,使用了大肠杆菌、脆弱拟杆菌和无菌粪便佐剂的混合腹膜炎模型。使用了三种转化的大肠杆菌菌株:一种强烈分泌活性溶血素(WAF 270),第二种分泌活性溶血素但量减少(WAF 260),第三种不产生溶血素(WAF 108)。在等量接种这三种菌株后,相对于其他菌株,WAF 270产生了明显增加的致死率,并且从宿主中回收的大肠杆菌和脆弱拟杆菌数量增加。在诱导腹膜炎后,强溶血性和非溶血性菌株之间,腹腔内pH值、红细胞裂解程度以及腹腔内白细胞的募集和活力变化存在显著差异。与WAF 108相比,用WAF 270诱导腹膜炎导致腹腔内pH值显著降低,大多数腹腔内红细胞裂解,可回收的存活白细胞显著减少。因此,大肠杆菌在腹腔内产生溶血素不仅可能改变宿主控制溶血性菌株本身的能力,还可能改变宿主控制其他生物体的能力。