Development of Bacterial Therapeutics Targeting Bacterial Vaginosis-Associated Bi

针对细菌性阴道病相关双歧杆菌的细菌疗法的开发

基本信息

批准号：
7925857
负责人：
Laurel A. Lagenaur
金额：
$ 19.85万
依托单位：
OSEL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7925857
关键词：
Accounting Anogenital venereal warts Antibiotic Resistance Antibiotic Therapy Antibiotics Atopobium vaginae Bacteria Bacterial Vaginosis Biological Products Biomedical Engineering Biopsy California Chlamydia Chromosomes Clinical Clinical Trials Coculture Techniques Collaborations Communities Complement Complex Development Discipline of obstetrics Disease Ecology Evolution Exhibits Failure Female of child bearing age Functional disorder Gardnerella Gardnerella vaginalis Genes Genital system Genitourinary system Gonorrhea Gynecologic HIV HIV Entry Inhibitors HIV-1 Heterosexuals Human Human Herpesvirus 2 Hydrogen Peroxide In Vitro Infection Intervention Investigation Lactobacillus Lead Length Life Light Microbial Biofilms Modeling Organism Outcome Pelvic Inflammatory Disease Phase II Clinical Trials Plasmids Positioning Attribute Predisposing Factor Pregnancy Outcome Prevalence Prevention Public Health Recurrence Regimen Reproductive Tract Infections Research Sexually Transmitted Diseases Surface Syndrome System Therapeutic Tissues Trichomonas Universities Urinary tract infection Vagina Viral Virus Woman Work burden of illness clinical practice effective therapy innovation microbial microbial community microbicide microorganism novel novel therapeutic intervention prevent public health relevance therapeutic target trait transmission process vaginal lactobacilli

项目摘要

DESCRIPTION (provided by applicant): This application focuses on the development of a novel bacterial therapeutics targeting bacterial vaginosis (BV)-associated biofilm for the prevention and treatment of recurrent BV using a novel strain of Lactobacillus jensenii with a disrupted pox1 gene in the chromosome that exhibits highly potent activity against a Gardnerella vaginalis strain (ATCC 14018). As an important step to pursue this biofilm intervention strategy, we propose to further evaluate in vitro efficacy of this novel strain to inhibit clinical vaginal isolates of G. vaginalis and Atopobium vaginae in a co-culture model, and ability to prevent the development of Gardnerella- specific biofilm. BV is the most common infection of the reproductive tract among women of childbearing age globally. Control of BV recurrence has emerged as a global issue of concern, in light of its significant prevalence and pathophysiology among women of childbearing age. Epidemiologically, this disruption in vaginal ecology can lead to a serious disease burden of adverse obstetric and gynecologic outcomes, including adverse pregnancy outcomes and pelvic inflammatory disease. BV resembles a sexually transmitted disease (STD) and is positively associated with the acquisition of other STD. Moreover, BV is prominent in regions of the world associated with high HIV transmission rates and enhances viral replication and genital tract shedding of the HIV-1 and HSV-2 viruses, thereby further promoting the spread of STD. BV is a complex polymicrobial syndrome resulting from the depletion of the normal H2O2-producing lactobacilli in the vagina, overgrowth of BV-associated microorganisms, and the establishment of an adherent Gardnerella/Atopobium-specific biofilm. There are no long-term therapies for curing and preventing this frequently recurring BV condition. The recommended antibiotic treatments, the mainstay of current therapy, fail to eradicate biofilm that is an important predisposing factor for BV recurrence. There is an urgent need to develop innovative therapeutic approaches to target BV-associated biofilm. Successful completion of the proposed studies would position us to pursue potential clinical investigations to evaluate biofilm intervention strategies using bioengineered vaginal Lactobacillus. In combination with current antibiotic regimen, this product concept may have a great potential to shift current research or clinical practice paradigms for an effective treatment and prevention of recurrent BV globally. It would decrease the economical burden from repetitive treatments and potential adverse obstetric and gynecologic outcomes, while re-establishing a Lactobacillus-dominant healthy vaginal flora. PUBLIC HEALTH RELEVANCE:

DESCRIPTION (provided by applicant): This application focuses on the development of a novel bacterial therapeutics targeting bacterial vaginosis (BV)-associated biofilm for the prevention and treatment of recurrent BV using a novel strain of Lactobacillus jensenii with a disrupted pox1 gene in the chromosome that exhibits highly potent activity against a Gardnerella vaginalis strain (ATCC 14018).作为采用这种生物膜干预策略的重要一步，我们建议在共培养模型中进一步评估这种新型菌株的体外疗效，以抑制阴道和阴道的临床阴道分离株，并抑制gardnerella-exteralla-exterlella生物膜的发展。 BV是全球生育年龄妇女生殖道的最常见感染。鉴于育龄妇女在育龄妇女中，对BV复发的控制已成为全球关注的全球问题。从流行病学上讲，阴道生态学中的这种破坏会导致严重的疾病负担，包括不良产科和妇科结局，包括不良妊娠结局和骨盆炎症性疾病。 BV类似于性传播疾病（STD），与获得其他性病的获取呈正相关。此外，BV在与高艾滋病毒传播率相关的世界中很突出，并增强了HIV-1和HSV-2病毒的病毒复制和生殖道脱落，从而进一步促进了STD的传播。 BV是一种复杂的多生物综合征，是由于阴道中正常的H2O2产生乳酸乳酸的耗竭，BV相关的微生物的过度生长以及建立了耐粘附的Gardnerella/Atopobium-apobium-bobium-trecifium-trecific Biofilm。没有长期治愈和防止这种经常发生的BV疾病的疗法。推荐的抗生素治疗是当前疗法的主要阶段，无法消除生物膜，这是BV复发的重要诱发因素。迫切需要开发创新的治疗方法来靶向与BV相关的生物膜。成功完成拟议的研究将使我们能够使用生物工程的阴道乳酸杆菌进行潜在的临床研究，以评估生物膜干预策略。结合当前的抗生素方案，该产品概念可能具有巨大的潜力，可以改变当前的研究或临床实践范例，以有效地治疗和预防全球复发性BV。这将减轻重复治疗以及潜在的不良产科和妇科结果的经济负担，同时重新建立乳酸杆菌的健康阴道菌群。公共卫生相关性：