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

• 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
• 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

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:

描述（由申请人提供）：本申请集中于开发靶向细菌性阴道病（BV）相关生物膜的新型细菌治疗剂，用于使用染色体中具有破坏的pox 1基因的詹氏乳杆菌（Lactobacillus jensenii）的新型菌株预防和治疗复发性BV，所述詹氏乳杆菌菌株对阴道加德纳菌菌株（ATCC 14018）表现出高度有效的活性。作为追求这种生物膜干预策略的重要一步，我们建议进一步评估这种新菌株抑制临床阴道G.在共培养模型中的阴道加德纳菌属和阴道奇异菌属的生物膜，以及防止加德纳菌属特异性生物膜发展的能力。BV是全球育龄妇女中最常见的生殖道感染。鉴于其在育龄妇女中的显著患病率和病理生理学，控制BV复发已成为一个全球关注的问题。在流行病学上，阴道生态的这种破坏可能导致不良产科和妇科结局的严重疾病负担，包括不良妊娠结局和盆腔炎。BV类似于性传播疾病（STD），与其他STD的获得呈正相关。此外，BV在世界上与高HIV传播率相关的区域中是突出的，并且增强了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是一种复杂的多微生物综合征，由阴道中正常的产生H2 O2的乳酸杆菌的消耗、BV相关微生物的过度生长以及粘附的加德纳菌/阿托泊菌属特异性生物膜的建立引起。目前还没有长期的治疗方法来治愈和预防这种经常复发的BV疾病。推荐的抗生素治疗是目前治疗的主要手段，但未能根除生物膜，而生物膜是BV复发的重要诱发因素。迫切需要开发针对BV相关生物膜的创新治疗方法。成功完成拟议的研究将使我们能够进行潜在的临床研究，以评估生物工程阴道乳酸菌的生物膜干预策略。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式，以有效治疗和预防全球复发性BV。它将减少重复治疗的经济负担和潜在的不良妇产科结局，同时重建乳酸杆菌占优势的健康阴道植物群。 公共卫生关系：