Material and Methods

Abstract

Candida albicans is the most important Candida species causing vulvovaginal candidiasis (VVC). VVC has significant medical and economical impact on women's health and wellbeing. While current antifungal treatment is reasonably effective, supportive and preventive measures such as application of probiotics are required to reduce the incidence of VVC. We investigated the potential of the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 towards control of C. albicans. In vitro experiments demonstrated that lactic acid at low pH plays a major role in suppressing fungal growth. Viability staining following cocultures with lactobacilli revealed that C. albicans cells lost metabolic activity and eventually were killed. Transcriptome analyses showed increased expression of stress-related genes and lower expression of genes involved in fluconazole resistance, which might explain the increased eradication of Candida in a previous clinical study on conjoint probiotic therapy. Our results provide insights on the impact of probiotics on C. albicans survival.

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Introduction

Mucosal infections by Candida albicans and related non-albicans Candida species are some of the most frequently encountered infections in modern medicine. Oral thrush and vulvovaginal candidiasis (VVC) amass the largest numbers of incidences among mucocutaneous Candida infections. While most forms of candidiasis affect immunocompromised individuals, VVC is commonly encountered by millions of otherwise healthy women. Estimates on the occurrence of VVC point to at least one episode of VVC in 75% of all women [1–3]. Clinical signs of vaginitis appear when the balance between the host and fungal colonization is disrupted, for example, by antibiotic suppression of beneficial components of the bacterial vaginal microbiota. Of note, unlike bacterial vaginosis (BV), the condition is not associated with a depletion of lactobacilli per se. Recurrent VVC, defined as at least four episodes in one year, affects a subpopulation, the treatment of whom requires long-term antifungal therapy [4]. After BV, VVC is the second most common cause of vaginitis, affecting about 40% of women with vaginal complaints [5]. In the USA, diagnosis and treatment of VVC and the concomitant loss of productivity was last estimated in 1995 to cost US$ 1.8 billion [6].

While the treatment of VVC is relatively effective, it has been suggested that patients could benefit from restoration of the vaginal microbiota and/or modulation of the local mucosal immune response via supplementation with probiotics. Furthermore, some non-albicans Candida species are inherently more resistant to antifungal agents and therefore can pose a greater challenge to treatment. Establishment of a healthy vaginal microbiota using beneficial Lactobacillus strains might be a supportive and preventive measure against VVC. A recent randomized, double-blind and placebo-controlled trial by Martinez and coworkers has shown that Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 increased the efficacy of antifungal agents in women diagnosed with VVC [7]. In a related in vitro study it was also noted that these probiotics had the potential to inhibit C. albicans, the most common cause of VVC [8].

In the present study, the objective was to learn more about the molecular mechanisms of C. albicansgrowth inhibition by the probiotic strains using microbiological and genome-wide expression analyses.

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Material and Methods

Date: 2016-01-03; view: 832