Protective Properties of S-layer Protein 2 from Lactobacillus crispatus 2029 against Candida albicans Infections

Abstract

Previously, the protective role of the S-layer protein 2 (Slp2) of the vaginal Lactobacillus crispatus 2029 (LC2029) strain against foodborne pathogens Campylobacter jejuni, Salmonella enterica serovar Enteritidis, and Escherichia coli O157:H was demonstrated. We demonstrate the new roles of the Slp2-positive LC2029 strain and soluble Slp2 against C. albicans infections. We show that LC2029 bacteria can adhere to the surface of the cervical epithelial HeLa cells, prevent their contact with C. albicans, and block yeast transition to a pathogenic hyphal form. Surface-bound Slp2 provides the ability for LC2029 to co-aggregate with various C. albicans strains, including clinical isolates. C. albicans-induced necrotizing epithelial damage is reduced by colonization with the Slp2-positive LC2029 strain. Slp2 inhibits the adhesion of various strains of C. albicans to different human epithelial cells, blocks yeast transition to a pathogenic hyphal form, and prevents the colonization and pathogenic infiltration of mucosal barriers. Only Slp2 and LC2029 bacteria stimulate the production of protective human β-defensin 3 in various epithelial cells. These findings support the anti-Candida albicans potential of the probiotic LC2029 strain and Slp2 and form the basis for further research on their ability to prevent and manage invasive Candida infections.

Keywords: Candida albicans; Lactobacillus crispatus; S-layer protein 2; anti-adhesive effect; anti-pathogenic potential; antifungal agent; probiotic bacteria.

Figure 1

Inhibitory effects of the LC2029 strain on the transition of C. albicans yeast form to hyphal. Optical microscopy (bar—10 µm). (A) Yeast form of C. albicans strain ATCC 10231. (B) Monolayer (formed by 100%) of intact immature HeLa cells. (C) Intensive transition of C. albicans yeast form to hyphal on intact monolayer of HeLa cells. All cells of the C. albicans yeast form, after being added to the intact HeLa monolayer, turned into hyphal form after 2 h of joint cultivation. (D) The monolayer (formed by100%) of immature HeLa cells is protected by cells of strain LC2029 in the adhered state. (E) The monolayer (formed by 70–80%) of immature HeLa cells is protected by cells of the LC2029 strain in the adhered state. Cells of the LC2029 strain are also visible in the nutrient medium in a suspension state. Thirty minutes after the introduction of the C. albicans in yeast form into the wells (the ratio of LC2029 strain/C. albicans yeast form is 100/1 CFU/mL), the cells of the LC2029 strain in the nutrient medium in suspension form co-aggregates with the C. albicans yeast form. (F) Co-aggregates of strain LC2029 cells with C. albicans cells in yeast form are removed when the culture medium is replaced or washed once by PBS. Only single C. albicans cells in yeast form are visible in the field of view HeLa cells.