Natural antimicrobials against bacterial vaginosis

对抗细菌性阴道病的天然抗菌剂

基本信息

批准号：
7140077
负责人：
Michael Chikindas
金额：
$ 18.67万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7140077
关键词：
Lactobacillus acidity /alkalinity alternatives to animals in research antibacterial agents antibiotics bacteriocin biotherapeutic agent chemoprevention drug interactions drug screening /evaluation microorganism culture microorganism interaction pharmacokinetics reproductive system infection vagina disorder

项目摘要

DESCRIPTION (provided by applicant): Bacterial vaginosis is a complex multi-microbial infection associated with the depletion of lactobacilli, the major flora of a healthy vagina and the overgrowth of Gardnerella vaginalis, Peptostreptococcus spp. and Prevotella bivia. BV may lead to premature labor. Endotoxins produced by the BV-associated bacteria cause serious brain/CNS damage in developing fetuses. Healthy vaginal Lactobacillus rhamnosus strain 160 produces an antimicrobial peptide, bacteriocin, designated as lactocin 160, which is active against BV associated microorganisms. We will examine our major hypothesis that this novel ribosomally-synthesized peptide is a potent antimicrobial agent for the prophylaxis and treatment of BV through the following three specific aims. We will determine lactocin 160's stability, safety, and spectrum of antimicrobial activity against BV associated vaginal pathogens. We expect lactocin 160 to be stable (alone and in combination with the selected natural antimicrobials), to have a broad range of antimicrobial activity against vaginal pathogens, and to be safe for human use (Specific Aim 1). Investigation of the mechanism of action by which lactocin 160 inhibits BV-associated microorganisms will lead to the understanding of the interaction between the cellular membrane and the peptide. We will determine whether one or both components of the Proton Motif Force are inhibited by lactocin 160 and if its activity is voltage-dependant, in other words, influenced by the growth phase of the pathogens. We will find out if ATP in the bacteriocin-treated cells will be hydrolyzed intracellularly, or will leak off the cell (Specific Aim 2). Finally, we will prove that lactocin 160 has increased bactericidal activity against vaginal pathogens at low pH established specifically by lactic acid and when combined with synergistically acting natural and safe antimicrobials such as Zn lactate, saponin, and Poly- lysine, all of which have a mechanism of antimicrobial action different from lactocin 160 (Specific Aim 3). Our research will lead to a new approach for BV prophylaxis and treatment.

描述（由申请人提供）：细菌性阴道病是一种复杂的多微生物感染，与乳酸杆菌的耗竭相关，健康阴道的主要菌群和gardnerella daginalla daginaliss，Peptoptoptopoccoccoccus spp。和prevotella bivia。 BV可能导致早产。由BV相关细菌产生的内毒素在发育中的胎儿中导致严重的大脑/CNS损害。健康的阴道乳杆菌160产生一种抗菌肽，细菌素，被指定为乳糖素160，它具有活性，可对BV相关的微生物进行活性。我们将研究我们的主要假设，即这种新型的核糖体合成肽是通过以下三个特定目的通过以下三个特定目标来预防和治疗BV的有效抗菌剂。我们将确定乳糖素160对BV相关的阴道病原体的抗菌活性的稳定性，安全性和光谱。我们预计乳糖素160是稳定的（单独并与所选天然抗菌剂），对阴道病原体具有广泛的抗菌活性，并且可以安全地使用人类使用（特定目标1）。研究乳糖素160抑制BV相关微生物的作用机理的研究将导致对细胞膜与肽之间的相互作用的理解。我们将确定质子基序的一个或两个成分是否被乳糖素160抑制，并且其活性是否依赖电压依赖性，换句话说，受病原体生长阶段的影响。我们将找出细菌毒素处理细胞中的ATP是细胞内水解的，还是会从细胞中泄漏（特定的AIM 2）。最后，我们将证明，乳酸素160在低pH值下的杀菌活性增加，当时是通过乳酸酸特异性建立的，并且与具有协同作用的天然和安全抗菌抗菌作用（如锌乳酸，皂苷和多肌氨酸）结合使用，这些抗蛋白质和多伴侣都具有与抗微生物作用的机制不同的。我们的研究将为BV预防和治疗提供新的方法。