The vaginal microbiota of healthy, fertile women is dominated by lactobacilli. As a defence mechanism, these bacteria produce HO to discourage colonization of the vagina by undesirable micro-organisms. In particular, CECT 4306 is a strong producer of HO and has been found to protect itself from the bactericidal effects of this compound through the activity of extracellular peroxidases. However, this peroxidase activity is dependent on the presence of Fe, which is found in elevated concentrations in the vaginal mucosa as a consequence of the menstrual discharge. The aim of the present work was to evaluate whether Fe is able to modulate other potential probiotic properties of strain 4306. We found that Fe enhances the adhesion of CECT 4306 to mucin and to HT-29 and HT-29 MTX cells, and, in addition, improves the anti-inflammatory profile, as judged by an increase in the ratio of IL-10/IL-12p70 that were secreted by macrophages. A comparison of total, secreted and surface proteins produced in the presence and absence of Fe revealed significant differences in the concentration of the moonlighting protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In conclusion, Fe seems to improve the probiotic characteristics of CECT 4306, and future research of the interactions of this strain with its vaginal environment may reveal further information about different aspects of its probiotic potential.


Article metrics loading...

Loading full text...

Full text loading...



  1. Andreu A., Stapleton A. E., Fennell C. L., Hillier S. L., Stamm W. E. (1995). Hemagglutination, adherence, and surface properties of vaginal Lactobacillus species. J Infect Dis 171, 12371243. [View Article][PubMed] [Google Scholar]
  2. Beaussart A., Rolain T., Duchêne M. C., El-Kirat-Chatel S., Andre G., Hols P., Dufrêne Y. F. (2013). Binding mechanism of the peptidoglycan hydrolase Acm2: low affinity, broad specificity. Biophys J 105, 620629. [View Article][PubMed] [Google Scholar]
  3. Biagi E., Vitali B., Pugliese C., Candela M., Donders G. G., Brigidi P. (2009). Quantitative variations in the vaginal bacterial population associated with asymptomatic infections: a real-time polymerase chain reaction study. Eur J Clin Microbiol Infect Dis 28, 281285. [View Article][PubMed] [Google Scholar]
  4. Boris S., Suárez J. E., Barbés C. (1997). Characterization of the aggregation promoting factor from Lactobacillus gasseri, a vaginal isolate. J Appl Microbiol 83, 413420. [View Article][PubMed] [Google Scholar]
  5. Boris S., Suárez J. E., Vázquez F., Barbés C. (1998). Adherence of human vaginal lactobacilli to vaginal epithelial cells and interaction with uropathogens. Infect Immun 66, 19851989.[PubMed] [Google Scholar]
  6. Boskey E. R., Cone R. A., Whaley K. J., Moench T. R. (2001). Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod 16, 18091813. [View Article][PubMed] [Google Scholar]
  7. Cohen, M. S., Black, J. R., Proctor, R. A. & Sparling, P. F. (1984). Host defences and the vaginal mucosa. A re-evaluation. Scand J Urol Nephrol Suppl86, 13–22.
  8. Courtney H. S., Ofek I., Penfound T., Nizet V., Pence M. A., Kreikemeyer B., Podbielski A., Hasty D. L., Dale J. B. (2009). Relationship between expression of the family of M proteins and lipoteichoic acid to hydrophobicity and biofilm formation in Streptococcus pyogenes . PLoS ONE 4, e4166. [View Article][PubMed] [Google Scholar]
  9. Doderlein A. S. G. (1982).Das Scheindensekret und seine bedeutung fur das puerperalfieber. Leipzig: O Durr. [Google Scholar]
  10. FAO/WHO (2006). Probiotics in food. Health and nutritional properties and guidelines for evaluation. FAO Food and Nutritional paper No 85 (ISBN 92-5-105513-0).
  11. Fettweis J. M., Serrano M. G., Girerd P. H., Jefferson K. K., Buck G. A. (2012). A new era of the vaginal microbiome: advances using next-generation sequencing. Chem Biodivers 9, 965976. [View Article][PubMed] [Google Scholar]
  12. Geshnizgani A. M., Onderdonk A. B. (1992). Defined medium simulating genital tract secretions for growth of vaginal microflora. J Clin Microbiol 30, 13231326.[PubMed] [Google Scholar]
  13. Gueimonde M., Tölkkö S., Korpimäki T., Salminen S. (2004). New real-time quantitative PCR procedure for quantification of bifidobacteria in human fecal samples. Appl Environ Microbiol 70, 41654169. [View Article][PubMed] [Google Scholar]
  14. Karlsson M., Jass J. (2012). Lactobacilli differently regulate expression and secretion of CXCL8 in urothelial cells. Benef Microbes 3, 195203. [View Article][PubMed] [Google Scholar]
  15. Kechaou N., Chain F., Gratadoux J. J., Blugeon S., Bertho N., Chevalier C., Le Goffic R., Courau S., Molimard P. et al. (2013). Identification of one novel candidate probiotic Lactobacillus plantarum strain active against influenza virus infection in mice by a large-scale screening. Appl Environ Microbiol 79, 14911499. [View Article][PubMed] [Google Scholar]
  16. Kinoshita H., Uchida H., Kawai Y., Kawasaki T., Wakahara N., Matsuo H., Watanabe M., Kitazawa H., Ohnuma S. et al. (2008). Cell surface Lactobacillus plantarum LA 318 glyceraldehyde-3-phosphate dehydrogenase (GAPDH) adheres to human colonic mucin. J Appl Microbiol 104, 16671674. [View Article][PubMed] [Google Scholar]
  17. Laemmli U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680685. [View Article][PubMed] [Google Scholar]
  18. Lesuffleur T., Roche F., Hill A. S., Lacasa M., Fox M., Swallow D. M., Zweibaum A., Real F. X. (1995). Characterization of a mucin cDNA clone isolated from HT-29 mucus-secreting cells. The 3′ end of MUC5AC?J Biol Chem 270, 1366513673. [View Article][PubMed] [Google Scholar]
  19. Macklaim J. M., Gloor G. B., Anukam K. C., Cribby S., Reid G. (2011). At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc Natl Acad Sci U S A 108 (Suppl 1), 46884695. [View Article][PubMed] [Google Scholar]
  20. Martín R., Suárez J. E. (2010). Biosynthesis and degradation of H2O2 by vaginal lactobacilli. Appl Environ Microbiol 76, 400405. [View Article][PubMed] [Google Scholar]
  21. Martín R., Soberón N., Vázquez F., Suárez J. E. (2008). [Vaginal microbiota: composition, protective role, associated pathologies, and therapeutic perspectives]. Enferm Infecc Microbiol Clin 26, 160167.[PubMed][CrossRef] [Google Scholar]
  22. Martín R., Sánchez B., Suárez J. E., Urdaci M. C. (2012). Characterization of the adherence properties of human Lactobacilli strains to be used as vaginal probiotics. FEMS Microbiol Lett 328, 166173. [View Article][PubMed] [Google Scholar]
  23. Martín R., Miquel S., Langella P., Bermúdez-Humarán L. G. (2014). The role of metagenomics in understanding the human microbiome in health and disease. Virulence 5, 413423. [View Article][PubMed] [Google Scholar]
  24. Pavlova S. I., Kilic A. O., Kilic S. S., So J. S., Nader-Macias M. E., Simoes J. A., Tao L. (2002). Genetic diversity of vaginal lactobacilli from women in different countries based on 16S rRNA gene sequences. J Appl Microbiol 92, 451459. [View Article][PubMed] [Google Scholar]
  25. Rochat T., Boudebbouze S., Gratadoux J. J., Blugeon S., Gaudu P., Langella P., Maguin E. (2012). Proteomic analysis of spontaneous mutants of Lactococcus lactis: involvement of GAPDH and arginine deiminase pathway in H2O2 resistance. Proteomics 12, 17921805. [View Article][PubMed] [Google Scholar]
  26. Rose W. A. II, McGowin C. L., Spagnuolo R. A., Eaves-Pyles T. D., Popov V. L., Pyles R. B. (2012). Commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures. PLoS ONE 7, e32728. [View Article][PubMed] [Google Scholar]
  27. Saad N., Urdaci M., Vignoles C., Chaignepain S., Tallon R., Schmitter J. M., Bressollier P. (2009). Lactobacillus plantarum 299v surface-bound GAPDH: a new insight into enzyme cell walls location. J Microbiol Biotechnol 19, 16351643. [View Article][PubMed] [Google Scholar]
  28. Sánchez B., Bressollier P., Urdaci M. C. (2008). Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host immunomodulation and molecular cross-talking with the host. FEMS Immunol Med Microbiol 54, 117. [View Article][PubMed] [Google Scholar]
  29. Sánchez B., Schmitter J. M., Urdaci M. C. (2009). Identification of novel proteins secreted by Lactobacillus plantarum that bind to mucin and fibronectin. J Mol Microbiol Biotechnol 17, 158162. [View Article][PubMed] [Google Scholar]
  30. Sobel J. D. (2000). Bacterial vaginosis. Annu Rev Med 51, 349356. [View Article][PubMed] [Google Scholar]
  31. Song Y. L., Kato N., Matsumiya Y., Liu C. X., Kato H., Watanabe K. (1999). Identification of and hydrogen peroxide production by fecal and vaginal lactobacilli isolated from Japanese women and newborn infants. J Clin Microbiol 37, 30623064.[PubMed] [Google Scholar]
  32. Tallon R., Arias S., Bressollier P., Urdaci M. C. (2007). Strain- and matrix-dependent adhesion of Lactobacillus plantarum is mediated by proteinaceous bacterial compounds. J Appl Microbiol 102, 442451. [View Article][PubMed] [Google Scholar]
  33. Thorsen P., Jensen I. P., Jeune B., Ebbesen N., Arpi M., Bremmelgaard A., Møller B. R. (1998). Few microorganisms associated with bacterial vaginosis may constitute the pathologic core: a population-based microbiologic study among 3596 pregnant women. Am J Obstet Gynecol 178, 580587. [View Article][PubMed] [Google Scholar]
  34. Vélez M. P., De Keersmaecker S. C., Vanderleyden J. (2007). Adherence factors of Lactobacillus in the human gastrointestinal tract. FEMS Microbiol Lett 276, 140148. [View Article][PubMed] [Google Scholar]
  35. Verhelst R., Verstraelen H., Claeys G., Verschraegen G., Delanghe J., Van Simaey L., De Ganck C., Temmerman M., Vaneechoutte M. (2004). Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol 4, 16. [View Article][PubMed] [Google Scholar]
  36. Vitali B., Pugliese C., Biagi E., Candela M., Turroni S., Bellen G., Donders G. G., Brigidi P. (2007). Dynamics of vaginal bacterial communities in women developing bacterial vaginosis, candidiasis, or no infection, analyzed by PCR-denaturing gradient gel electrophoresis and real-time PCR. Appl Environ Microbiol 73, 57315741. [View Article][PubMed] [Google Scholar]
  37. Wilks M., Wiggins R., Whiley A., Hennessy E., Warwick S., Porter H., Corfield A., Millar M. (2004). Identification and H2O2 production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol 42, 713717. [View Article][PubMed] [Google Scholar]
  38. Zhao J. J., Feng X. P., Zhang X. L., Le K. Y. (2012). Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of IL1B, IL6, and IL8 by gingival epithelial cells. Inflammation 35, 13301337. [View Article][PubMed] [Google Scholar]
  39. Zhou X., Bent S. J., Schneider M. G., Davis C. C., Islam M. R., Forney L. J. (2004). Characterization of vaginal microbial communities in adult healthy women using cultivation-independent methods. Microbiology 150, 25652573. [View Article][PubMed] [Google Scholar]

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error