Enhanced antifungal activity of bovine lactoferrin-producing probiotic Lactobacillus casei in the murine model of vulvovaginal candidiasis

Hong Liao,Shanling Liu,He Wang,Zhenjun Liu,Hang Su

doi:10.1186/s12866-018-1370-x

Hong Liao, Shanling Liu + Show 3 more

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https://doi.org/10.1186/s12866-018-1370-x

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Abstract

BackgroundVulvovaginal candidiasis (VVC) is a common vaginitis caused by Candida species,a frequently recurring condition. Fungal azole-resistant strains with azole-resistance have developed for long and wide explosion to the first-line antifungal azole agent. Bovine lactoferrin (BLF) is a protein from transferrin family secreted by the bovine mammary tissue. Its various biological functions are well known, especially the pronounced antifungal activity.ResultsIn the current study, we constructed a Lactobacillus casei strain (L.casei/pPG612.1-BLF), which secreted BLF encoded by a mature secretion vector plasmid pPG612.1, and evaluated its antifungal activity in vitro and in vivo. In a two-layer agar plate in vitro assay, the number of C. albicans CFUs decreased and the average colony size shrunk upon exposure to L. casei/pPG612.1-BLF. In a murine VVC model, the infection burden of mice intra-vaginally pre-inoculated with L. casei/pPG612.1-BLF was lower than in control groups. Furthermore, the infection burden in mice with VVC was reduced when the animals were continually given L. casei/pPG612.1-BLF as a topical treatment for 5 days.ConclusionCombined, these results suggested that the L. casei/pPG612.1-BLF strain is a promising preventative and therapeutic anti-VVC agent, highlighting the possibility of employing the probiotic L. casei as a vehicle for biotherapy in the female genital tract and exploiting the natural antibiotic antimicrobial peptides for other applications.

Highlights

Vulvovaginal candidiasis (VVC) is a common vaginitis caused by Candida species,a frequently recurring condition
Amplification of the BamHI and XhoI sites of the plasmid pPG612.1-Bovine lactoferrin (BLF) isolated from the L. casei/pPG612.1-BLF strain resulted in 500-bp product; sequencing of the PCR products verified the successful insertion of the BLF coding sequence in plasmid pPG612.1(data not shown)
Fungicidal effects of L. casei/pPG612.1-BLF against C.albicans in vitro We developed a two-layer agar dish assay, which allowed C. albicans to be directly exposed to the secretions of the L. casei/pPG612.1-BLF; i.e., L. casei cells were grown anaerobically in the bottom Mann Rogosa Sharpe (MRS) layer, while C. albicans cells were grown on the surface of the top Sabouraud dextrose agar (SDA) layer

Summary

Introduction

Vulvovaginal candidiasis (VVC) is a common vaginitis caused by Candida species,a frequently recurring condition. Fungal azole-resistant strains with azole-resistance have developed for long and wide explosion to the first-line antifungal azole agent. Bovine lactoferrin (BLF) is a protein from transferrin family secreted by the bovine mammary tissue. Its various biological functions are well known, especially the pronounced antifungal activity. Vulvovaginal candidiasis (VVC) is the second most common infection disease in female genitourinary tract after bacterial vaginosis. It can affect up to 75% of women of childbearing age [1]. Symptoms, including burning pain, intense pruritus and abnormal “cheese-like” or watery vaginal discharge, are typical [2, 3]. Albicans (C. albicans), identified as the most common pathogen in VVC, is commensal fungi colonizing in female genitourinary tracts [4].

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