Lactobacillus Comparative Database

Genomic Sequencing of H202-Producing Lactobacillus Species that Dominates Microflora of Healthy Human Vagina

The vaginal microflora constitutes a dynamic ecosystem with important host defense capabilities that promote reproductive health. Within this ecosystem, the healthy human vagina is dominated by Lactobacillus species [2].

The species of lactobacilli most commonly isolated from the reproductive tracts of healthy women worldwide include L. crispatus, L. jensenii, L. gasseri, and L. iners [1, 3]. They are phylogenetically different from food and/or environmental Lactobacillus species. It should be noted that it is not clear why women preferentially harbor different Lactobacillus species, or none at all on the vaginal mucosa. As commensal bacteria, lactobacilli interact intimately with the host's mucosal immune system, and these interactions probably play an important role in shaping the composition of the vaginal microflora. These facultative anaerobes metabolize glucose to lactic acid, contributing to the maintenance of a low vaginal pH (4.0-4.5) that accounts for a major part of the non-specific defense of the vagina. An acidic pH has a significant antiviral effect against HIV and HSV as well as other urogenital pathogens.

The vagina represents a critical point of entry for most sexually transmitted infections (STIs). Epidemiologically, depletion of the hydrogen peroxide (H2O2) producing lactobacilli within the vaginal cavity is associated with establishment of bacterial vaginosis (BV), opportunistic infections, and an increased risk of acquiring HIV-1 and HSV-2 in women [4-7]. Additionally, a deficiency of lactobacilli has been linked to decreased rates of conception in women undergoing in vitro fertilization (IVF) procedures and is associated with spontaneous miscarriage and preterm delivery during pregnancy [8]. As recognized by the NIH, control and prevention of infections in the female reproductive tract are critical global and national health priorities because of the devastating impact on women and infants, and the inter-relationships with HIV/AIDS. As a result, the need to develop and evaluate a variety of tools and methods to define the complex ecosystem, interactions of vaginal flora and pathogens, and how one infection influences another is urgently recognized.

Lactobacillus Replacement Therapy

Although antibiotic therapy has been shown to eliminate BV-associated organisms, there is an extremely high recurrence rate, with up to 50% of patients experiencing recurrent infections (defined as 3 or more episodes within 12 months) [9]. Evidence suggests that recurrence is a result of failure to re-establish a normal vaginal flora following antimicrobial therapy [10]. Consequently, there has been considerable interest in non-antibiotic, ecological approaches to prevent BV recurrence by re-colonizing the vagina with lactobacilli. The intentional colonization of the human vagina with certain Lactobacillus strains has been shown to be both feasible and safe, and may reduce the risk of urinary tract infection [11, 12], yeast vaginitis, and BV [13, 14].

Osel, Inc.is developing a novel live microbicide, employing a H2O2-producing vaginal Lactobacillus, a natural component of the human vaginal microflora, as a self-renewing delivery vehicle for anti-HIV proteins, termed MucoCept. Osel aims at the intervention of pathogen transmission on mucosal surfaces and the development of a simple, cost-effective, and female-controlled preventative against heterosexual transmission of HIV in women [15].

References

  1. Antonio, M.A., Hawes, S.E., and Hillier, S.L. (1999). The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J Infect Dis 180, 1950-1956.
  2. Redondo-Lopez, V., Cook, R.L., and Sobel, J.D. (1990). Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. Rev Infect Dis 12, 856-872.
  3. Zhou, X., Bent, S.J., Schneider, M.G., Davis, C.C., Islam, M.R., and Forney, L.J. (2004). Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods. Microbiology (Reading, England) 150, 2565-2573.
  4. Taha, T.E., Hoover, D.R., Dallabetta, G.A., Kumwenda, N.I., Mtimavalye, L.A., Yang, L.P., Liomba, G.N., Broadhead, R.L., Chiphangwi, J.D., and Miotti, P.G. (1998). Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 12, 1699-1706.
  5. Cohn, M.A., Frankel, S.S., Rugpao, S., Young, M.A., Willett, G., Tovanabutra, S., Khamboonruang, C., VanCott, T., Bhoopat, L., Barrick, S., et al. (2001). Chronic inflammation with increased human immunodeficiency virus (HIV) RNA expression in the vaginal epithelium of HIV-infected Thai women. J Infect Dis 184, 410-417.
  6. Sha, B.E., Zariffard, M.R., Wang, Q.J., Chen, H.Y., Bremer, J., Cohen, M.H., and Spear, G.T. (2005). Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis. J Infect Dis 191, 25-32.
  7. Cherpes, T.L., Melan, M.A., Kant, J.A., Cosentino, L.A., Meyn, L.A., and Hillier, S.L. (2005). Genital tract shedding of herpes simplex virus type 2 in women: effects of hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus colonization. Clin Infect Dis 40, 1422-1428.
  8. Eckert, L.O., Moore, D.E., Patton, D.L., Agnew, K.J., and Eschenbach, D.A. (2003). Relationship of vaginal bacteria and inflammation with conception and early pregnancy loss following in-vitro fertilization. Infect Dis Obstet Gynecol 11, 11-17.
  9. Wilson, J. (2004). Managing recurrent bacterial vaginosis. Sex Transm Infect 80, 8-11.
  10. Hillier, S.L., Lipinski, C., Briselden, A.M., and Eschenbach, D.A. (1993). Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis. Obstet Gynecol 81, 963-967.
  11. Reid, G., and Bruce, A.W. (1995). Low vaginal pH and urinary-tract infection. Lancet 346, 1704.
  12. Kwok, L., Stapleton, A.E., Stamm, W.E., Hillier, S.L., Wobbe, C.L., and Gupta, K. (2006). Adherence of Lactobacillus crispatus to vaginal epithelial cells from women with or without a history of recurrent urinary tract infection. J Urol 176, 2050-2054; discussion 2054.
  13. Reid, G. (2001). Probiotic agents to protect the urogenital tract against infection. Am J Clin Nutr 73, 437S-443S.
  14. Anukam, K.C., Osazuwa, E., Osemene, G.I., Ehigiagbe, F., Bruce, A.W., and Reid, G. (2006). Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect 8, 2772-2776.
  15. Chang, T.L., Chang, C.H., Simpson, D.A., Xu, Q., Martin, P.K., Lagenaur, L.A., Schoolnik, G.K., Ho, D.D., Hillier, S.L., Holodniy, M., et al. (2003). Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proceedings of the National Academy of Sciences of the United States of America 100, 11672-11677.