Reid G, Chan R C, Bruce A W, Costerton J W
Infect Immun. 1985 Aug;49(2):320-4. doi: 10.1128/iai.49.2.320-324.1985.
Our previous studies have shown that indigenous bacteria are able to block the in vitro attachment of uropathogenic bacteria to human uroepithelial cells. In the present study, we applied the concept of competitive exclusion to an animal model. A chronic urinary tract infection was established in female rats with bacteria incorporated into agar beads injected periurethrally into the urinary bladder via a no. 3 French ureteral catheter. Five strains of uropathogenic organisms were used in the first set of experiments, and their colonization of the bladder and kidneys of the animals was confirmed up to 2 months after injection. The uropathogens stimulated an immune response, detected by serum antibodies against the uropathogens, and an inflammatory response noted in sections of the kidneys stained with hematoxylin and eosin. Using this animal model, we established the persistent adherence of bacteria in the urinary tract without the need for creation of obstruction or implantation of a foreign body. In a second set of experiments, an isolate of Lactobacillus casei GR1 taken from the urethra of a healthy woman was incorporated into agar beads, instilled within the rat bladders on day 1, and then swabbed twice weekly for 21 days onto the introitus before challenge with uropathogens instilled into the urinary bladder. In 21 of 25 animals, no uropathogenic bacteria were recovered from the bladder and kidney tissues up to 60 days after challenge, and no immune response was detected. Our results show that L. casei prevented onset of urinary tract infection in 84% of the animals tested. The lactobacilli appeared to exclude the uropathogens from colonizing the urinary tract, within the first 48 hours after challenge, and the net effect was a complete eradication of bacteria from the uroepithelium. It is hoped that the demonstration of a protective role for indigenous bacteria in preventing urinary tract infection in an animal model will lead to the application of this technology to prevent recurrent urinary tract infection in female patients.
我们之前的研究表明,本土细菌能够在体外阻断尿路致病菌与人尿道上皮细胞的黏附。在本研究中,我们将竞争排斥的概念应用于动物模型。通过一根3号法国输尿管导管经尿道周围向雌性大鼠膀胱内注射掺入琼脂珠的细菌,从而建立慢性尿路感染模型。在第一组实验中使用了5株尿路致病微生物,注射后长达2个月证实它们在动物的膀胱和肾脏中定殖。尿路致病菌刺激了免疫反应,可通过针对尿路致病菌的血清抗体检测到,并且在用苏木精和伊红染色的肾脏切片中观察到炎症反应。利用这个动物模型,我们建立了细菌在尿路中的持续黏附,而无需制造梗阻或植入异物。在第二组实验中,将从一名健康女性尿道分离出的干酪乳杆菌GR1掺入琼脂珠中,在第1天注入大鼠膀胱内,然后每周两次擦拭大鼠阴道口共21天,之后向膀胱内注入尿路致病菌进行攻击。在25只动物中的21只中,攻击后长达60天,在膀胱和肾脏组织中均未检测到尿路致病细菌,也未检测到免疫反应。我们的结果表明,干酪乳杆菌在84%的受试动物中预防了尿路感染的发生。乳酸杆菌似乎在攻击后的头48小时内阻止了尿路致病菌在尿路中定殖,最终结果是从尿道上皮完全清除了细菌。希望在动物模型中证明本土细菌在预防尿路感染方面的保护作用,将促使这项技术应用于预防女性患者复发性尿路感染。