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

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.

The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria

“…One of the most well-known characteristics of LF is that it is antibacterial (19,(144)(145)(146)(147)(148), antiviral (99,(149)(150)(151), antifungal (152)(153)(154), anti-inflammatory (26), and anti-carcinogenic (155).…”

The Impact of Lactoferrin on the Growth of Intestinal Inhabitant Bacteria

“…Recombinant Lactobacillus strains expressing Lf [126,127] may be future strategies to prevent and combat high-risk human infections, such as neonatal necrotizing enterocolitis [128]. As documented in murine models and clinical trials, pharmaceutical preparations containing bLf and probiotics or Lf-producing probiotic strains have been effective to combat vulvovaginal infections caused Candida albicans , Gardnerella vaginalis, or Atopobium vaginalis by restoring the microbiota in vulvovaginal tract [129,130,131]. These findings provide promising insights to control vulvovaginal infections caused resistant pathogens via microbiota modulation.…”

Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development

“…The anti-microbial activity has been described as the very first Lf function, linked to the ancestral host defense mechanisms to combat pathogens infections. This activity, evaluated in several in vitro [ 34 , 180 , 181 , 182 ] and in vivo [ 35 , 36 , 183 ] models, can be both dependent or independent of Lf iron binding ability [ 20 , 184 ]. Through its capability to chelate two ferric ions per molecule, Lf exerts a bacteriostatic action limiting microbial growth in infection sites by producing an iron-deficient environment [ 20 ].…”