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The female vaginal environment contains diverse microorganisms, and their interactions play significant roles in health and disease.  Lactobacillus  species are the predominant vaginal microorganisms in healthy women and relevant as a barrier to defense against pathogens, including  Candida albicans . The yeast-to-hyphae transition is believed to be a determinant of  C. albicans  pathogenesis. In this study, we investigated the effects of vaginal isolates of  L. crispatus  (seven strains),  L. gasseri  (six strains), and  L. jensenii  (five strains) on growth, hyphal formation and virulence-related genes expression of  C. albicans  ATCC 10231. We found that the  L. crispatus  showed the most significant antimicrobial activities in microplate-based liquid medium assay ( P  < 0.05). All seven cell-free supernatants (CFS) from  L. crispatus  strains reduced the growth of  C. albicans  by >60%. The effects might be due to their productions of some secretory antimicrobial compounds in addition to H 2 O 2  and organic acids. Furthermore, each of the CFS of  Lactobacillus  strains was found to significantly suppress the yeast-to-hyphae transition of  C. albicans  under hyphae-inducing conditions (RPMI 1640 medium supplemented with 10% fetal bovine serum). The hyphae inhibition rates of  C. albicans  treated by CFS from  L. crispatus ,  L. gasseri , and  L. jensenii  were 88.3 ± 3.02%, 84.9 ± 6.0%, and 81.9 ± 6.2%, respectively. Moreover, the expression of hyphae-specific genes ( ALS3 ,  HWP1 ,  ECE1 ,  EAP1 , and  SAP5 ) and transcriptional regulatory genes ( EFG1 ,  TEC1 , and  NRG1 ) were analyzed using quantitative real-time PCR. The results demonstrated that  L. crispatus  CFS significantly down-regulated the expression of hyphae-specific genes  ALS3  (0.140-fold)),  HWP1  (0.075-fold), and  ECE1  (0.045-fold), while up-regulated the expression of the negative transcriptional regulator gene  NRG1  with 1.911-fold. The antimicrobial compounds from  L. crispatus  B145 against  Candida  growth were heat stable and protease resistance, but those against hyphal formation were partially sensitive to the same treatments. Our novel findings suggest that  L. crispatus , a dominant  Lactobacillus  species associated with a healthy vagina, could strongly inhibit  C. albicans  growth and hyphal formation.  L. crispatus  might repress the expression of hyphae-specific genes ( ALS3 ,  HWP1 , and  ECE1 ) in a  NRG1 -dependent manner. Besides,  L. crispatus  B145 is highly worthwhile for probiotic investigation.

frontiers in microbiology

Antimicrobial Compounds Produced by Vaginal Lactobacillus crispatus Are Able to Strongly Inhibit Candida albicans Growth, Hyphal Formation and Regulate Virulence-related Gene Expressions