AUTHOR=Wang Shuai , Wang Qiangyi , Yang Ence , Yan Ling , Li Tong , Zhuang Hui 

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

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00564

DOI=10.3389/fmicb.2017.00564

ISSN=1664-302X

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