Live Biotherapeutics Drug Discovery Service for Fungal Infections

Overview

According to the site of disease, fungal infection is divided into superficial fungal infection and deep fungal infection. Fusariosis is a contagion that affects animals, plants as well as humans and is brought about by several fungi of the genera Fusarium. Fusarium species are the source for a diverse range of human infections, extending from superficial, and localized to disseminated with the most predominant being onychomycosis, keratitis, and skin infections. Biological control strategies are being increasingly explored. Several in vitro studies have proved Fusarium species are sensitive to different strains of lactic acid bacteria. Aspergillosis is the utmost habitual mold infection in human beings. The use of probiotics and postbiotics has opened a new avenue for the prevention and treatment of opportunistic infections such as aspergillosis which can be supplemented in the diet or added to medical formulations. It is important to emphasize that many probiotics that do not show a significant effect in vitro can be effective in vivo. Therefore, the evaluation and selection of potential probiotic bacteria should be a complex and multi-step process.

Probiotics as a New Generation of Biogenic Drugs to Fight Fungal Diseases

The need for biocontrol agents such as probiotic bacteria and their postbiotics has been anticipated as a substitute approach to treatment against opportunistic human fungal infections. Numerous studies with probiotic isolates and their culture filtrates (CFS) have shown efficient antibiofilm activity towards Candida spp. Applying probiotics to treat and prevent candida fungal infections is derived from the evidence that assured probiotic strains employ a defensive outcome in vivo by hindering the epithelial cells' adhesion and colonization by the infectious fungus to the mucosa, secretion of metabolites and also increasing epithelial cell immune defense mechanisms. The treatment and prevention with probiotics restore the natural microbiota with reward over conventional antifungals because they are non-toxic and do not persuade microbial resistance when administered in sufficient quantity, as a result, probiotics do not create adverse side effects and further modulate the immune system.

Mechanisms of Action of Probiotics

The mechanisms of action of probiotics can be divided into several groups: strengthening epithelial barriers, improving mucosal adhesion of the healthy microbiota, inhibiting the mucosal adhesion of pathogens, competitive exclusion of pathogens, production of antimicrobial compounds, and modulation of host immunity. While probiotic active cells and their metabolites have synergistic effects, cell-free secretions of probiotics also have antibacterial effects, which expands the application range of probiotics. Therefore, the discovery of more antibacterial probiotics that can be used for clinical treatment and the exploration of the antibacterial mechanism of probiotics may become the focus of future research on probiotics.

Fig.1 Mechanism of intestinal bacteria against C. albicans. (Cong, 2023)Fig.1 Mechanism of intestinal bacteria against C. albicans.1

Our Technologies for Investigation and Confirmation of the Antifungal Activity of Probiotics

  • Experiments for Investigation of Antifungal Potential of Probiotics In Vitro

Agar plate antagonism and liquid coculture were included. In the agar plate antagonism method, probiotics and indicator bacteria are introduced into the same plate, and the only difference is the order and mode of inoculation of the probiotic or indicator fungal pathogen. Incubation was then performed, and the diameter of the inhibition zone, the transparent zone surrounding the inoculation zone, was read out in millimeters.

  • The Discovery of Antifungal Mechanisms

Methods used to determine the mechanisms of antifungal activity of probiotics include the ability to inhibit virulence factors, changes in cell morphology, and apoptosis.

  • Ability to inhibit virulence factors
  • Germ tube and hyphal growth inhibition method
  • Spore germination inhibition assay of CFS
  • Scanning electron microscopy
  • Confocal laser scanning microscopy
  • Mechanism of cell death
  • Confirm the Antifungal Activity of Probiotics In Vivo-Animal Models

Animal models have an additional advantage in that antimicrobial efficacy can be determined at specific body sites for example thigh, peritoneum, lung, endocarditis, and meningitis can be evaluated.

Probiotics

The different Lactobacillus spp which have demonstrated potential antifungal activity against C. albicans include L. plantarum, L. fermentum, L. reuteri, L. rhamnosus, L. johnsonii, L. acidophilus, Lactobacillus paracasei, Lactobacillus pentosus, L. crispatus, L. gasseri, and L. vaginalis. The two standard probiotic cultures L. reuteri RC-14 and L. rhamnosus GR-1 have been repeatedly used to demonstrate their antifungal activity against different Candida species. The use of probiotics for the prevention and treatment of fungal infections, either alone or in combination with conventional antimicrobial agents, may open up new opportunities for antifungal therapy.

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Reference

  1. Cong, Liu, et al. "Intestinal bacteria-a powerful weapon for fungal infections treatment." Frontiers in Cellular and Infection Microbiology 13 (2023): 674.

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