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）：本申请重点开发一种针对细菌性阴道病 (BV) 相关生物膜的新型细菌疗法，用于预防和治疗复发性 BV，使用染色体中具有破坏的 pox1 基因的新型詹氏乳杆菌菌株，该菌株对阴道加德纳菌菌株 (ATCC 14018) 表现出高效活性。作为推行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型菌株在共培养模型中抑制阴道加德纳菌和阴道阿托波菌临床分离株的体外功效，以及防止加德纳菌特异性生物膜形成的能力。 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着患病率和病理生理学，控制 BV 复发已成为全球关注的问题。从流行病学角度来看，阴道生态的破坏可能导致不良妇产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)，并且与其他 STD 的感染呈正相关。此外，BV在世界上HIV传播率高的地区很突出，并增强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STD的传播。 BV 是一种复杂的多微生物综合征，由阴道内正常产生 H2O2 的乳酸杆菌耗尽、BV 相关微生物过度生长以及粘附的加德纳菌/Atopobium 特异性生物膜的建立引起。没有长期疗法可以治愈和预防这种经常复发的 BV 病症。推荐的抗生素治疗是当前治疗的支柱，但无法根除生物膜，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开展潜在的临床研究，以评估使用生物工程阴道乳杆菌的生物膜干预策略。与当前的抗生素治疗方案相结合，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，从而在全球范围内有效治疗和预防复发性 BV。它将减少重复治疗和潜在不良妇产科结果带来的经济负担，同时重建以乳杆菌为主的健康阴道菌群。 公共卫生相关性：