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: Thesaurus Terms: "aids Virus; Accounting; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Anogenital Venereal Warts; Antibiotic Agents; Antibiotic Drugs; Antibiotic Resistance; Antibiotic Therapy; Antibiotic Treatment; Antibiotics; Atopobium Vaginae; Bacteria; Bacterial Vaginosis; Biologic Products; Biological Agent; Biological Products; Biomedical Engineering; Biopsy; Body Tissues; California; Chlamydia; Chromosomes; Clinical; Clinical Trials; Clinical Trials, Phase Ii; Clinical Trials, Unspecified; Co-Culture; Cocultivation; Coculture; Coculture Techniques; Collaborations; Communities; Complement; Complement Proteins; Complex; Condyloma Accuminata; Condylomata Acuminata; Corynebacterium Vaginale; Development; Discipline Of Obstetrics; Disease; Disorder; Dysfunction; Ecology; Environmental Science; Evolution; Exhibits; Flr; Failure (Biologic Function); Female Of Child Bearing Age; Female Of Childbearing Age; Functional Disorder; Gardnerella; Gardnerella Vaginalis; Genes; Genital; Genital System, Female, Vagina; Genital System; Genitourinary; Genitourinary System; Gonococcal Infection; Gonorrhea; Gynecologic; H2o2; Hhv-2; Hiv; Hiv Entry Inhibitors; Hiv-1; Hiv-I; Hiv1; Hsv-2; Hsv2; Htlv-Iii; Haemophilus Vaginalis; Herpes Simplex Virus 2; Herpes Simplex Virus Type 2; Herpesvirus 2 (Alpha), Human; Herpesvirus 2, Human; Herpesvirus Progenitalis; Heterosexuals; Human; Human (Alpha) Herpes Virus 2; Human Herpesvirus 2; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type Iii; Human T-Cell Lymphotropic Virus Type Iii; Human T-Lymphotropic Virus Type Iii; Human Herpes Simplex Virus Type 2; Human Immunodeficiency Virus 1; Human, General; Hydrogen Peroxide; Hydrogen Peroxide (H2o2); Hydroperoxide; Immunodeficiency Virus Type 1, Human; In Vitro; Infection; Intervention; Intervention Strategies; Investigation; Lav-Htlv-Iii; Lactobacillus; Lead; Length; Life; Light; Lymphadenopathy-Associated Virus; Man (Taxonomy); Man, Modern; Microbial Biofilms; Microorganisms, General; Miscellaneous Antibiotic; Miyagawanella; Modeling; Obstetrics; Organism; Outcome; Pb Element; Pelvic Inflammatory Disease; Phase 2 Clinical Trials; Phase Ii Clinical Trials; Photoradiation; Physiopathology; Plasmids; Position; Positioning Attribute; Predisposing Factor; Pregnancy Outcome; Prevalence; Prevention; Public Health; Recurrence; Recurrent; Regimen; Reproductive Tract Infections; Research; Resistance To Antibiotics; Resistance, Antibiotic; Resistant To Antibiotics; Std; Sexually Transmitted Diseases; Sexually Transmitted Disorder; Sexually Transmitted Infection; Surface; Syndrome; System; System, Loinc Axis 4; Therapeutic; Tissues; Transmission; Trichomonas; Uti; Universities; Urinary Tract Infection; Urinary Tract Infectious Disease; Urogenital; Urogenital System; Vagina; Vaginal; Vaginitis, Bacterial; Vaginitis, Nonspecific; Venereal Diseases; Venereal Disorders; Venereal Infections; Viral; Virus; Virus-Hiv; Viruses, General; Warts, Genital; Warts, Venereal; Woman; Work; Antibiotic Resistant; Bedsonia; Bioengineering; Bioengineering/Biomedical Engineering; Biofilm; Biopharmaceutical; Biotherapeutic Agent; Burden Of Disease; Burden Of Illness; Clinical Investigation; Clinical Practice; Disease Burden; Disease/Disorder; Effective Therapy; Failure; Heavy Metal Pb; Heavy Metal Lead; Herpes Simplex Ii; Human T Cell Leukemia Virus Iii; Human T Lymphotropic Virus Iii; Human Alphaherpesvirus 2; Innovate; Innovation; Innovative; Interventional Strategy; Living System; Microbial; Microbial Community; Microbicidal; Microbicide; Microorganism; Novel; Novel Therapeutic Intervention; Pathophysiology; Phase 2 Study; Phase 2 Trial; Phase Ii Trial; Prevent; Preventing; Protocol, Phase Ii; Public Health Medicine (Field); Public Health Relevance; Study, Phase Ii; Therapeutic Target; Trait; Transmission Process; Treatment Of Bacterial Diseases; Treatment Of Bacterial Infectious Disease; Urogenital System (Genital Part); Urogenital System (Urinary Part); Vaginal Lactobacilli; Women Of Child Bearing Age; Women Of Childbearing Age; Years Of Life Lost To Disability; Years Of Life Lost To Disease"
