Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesianain the control of experimental candidiasis

Abstract

BackgroundAntimicrobial peptides are present in animals, plants and microorganisms and play a fundamental role in the innate immune response. Gomesin is a cationic antimicrobial peptide purified from haemocytes of the spider Acanthoscurria gomesiana. It has a broad-spectrum of activity against bacteria, fungi, protozoa and tumour cells. Candida albicans is a commensal yeast that is part of the human microbiota. However, in immunocompromised patients, this fungus may cause skin, mucosal or systemic infections. The typical treatment for this mycosis comprises three major categories of antifungal drugs: polyenes, azoles and echinocandins; however cases of resistance to these drugs are frequently reported. With the emergence of microorganisms that are resistant to conventional antibiotics, the development of alternative treatments for candidiasis is important. In this study, we evaluate the efficacy of gomesin treatment on disseminated and vaginal candidiasis as well as its toxicity and biodistribution.ResultsTreatment with gomesin effectively reduced Candida albicans in the kidneys, spleen, liver and vagina of infected mice. The biodistribution of gomesin labelled with technetium-99 m showed that the peptide is captured in the kidneys, spleen and liver. Enhanced production of TNF-α, IFN-γ and IL-6 was detected in infected mice treated with gomesin, suggesting an immunomodulatory activity. Moreover, immunosuppressed and C. albicans-infected mice showed an increase in survival after treatment with gomesin and fluconazole. Systemic administration of gomesin was also not toxic to the micConclusionsGomesin proved to be effective against experimental Candida albicans infection. It can be used as an alternative therapy for candidiasis, either alone or in combination with fluconazole. Gomesin's mechanism is not fully understood, but we hypothesise that the peptide acts through the permeabilisation of the yeast membrane leading to death and/or releasing the yeast antigens that trigger the host immune response against infection. Therefore, data presented in this study reinforces the potential of gomesin as a therapeutic antifungal agent in both humans and animals.

Thionin-like peptide from Capsicum annuum fruits: mechanism of action and synergism with fluconazole against Candida species

“…In a previous report [ 8 ], our research team isolated a plant-derived thionin, named Ca Thi, with strong antimicrobial activity against two pathogenic Candida species, as well as Escherichia coli and Pseudomonas aeruginosa . FLC in combination with AMPs resulting in promising therapeutic results against important human pathogens, such as C. albicans and Cryptococcus neoformans , has been demonstrated [ 16 , 17 ]. In this work we investigated whether the AMP Ca Thi could act synergistically with FLC.…”

Antifungal activity of biogenic tellurium nanoparticles against Candida albicans and its effects on squalene monooxygenase gene expression

“…C. albicans is an opportunistic commensal microorganism and categorized as normal flora. However, in immunocompromised patients, this fungus may cause skin, mucosal, or systemic infections . Te NPs moderately inhibit the growth of C. albicans by means of interaction with the metabolism of membrane sterols.…”

The Biological and Biophysical Properties of the Spider Peptide Gomesin

“…The original study reporting the isolation, synthesis, and biochemical characterisation of Gm included testing the cell viability on more than 40 microorganisms, including Gram-positive and Gram-negative bacteria, filamentous fungi and yeasts, and the eukaryotic parasite Leishmania amazonensis [ 1 ]. Since then, the anti-microbial activity of Gm has been confirmed by a number of independent studies [ 3 , 7 , 8 , 9 , 11 , 34 ]. Table 1 summarises the minimum inhibitory concentrations (MIC) for the most commonly-tested microorganisms reported in these studies.…”

“…To the best of our knowledge, only two in-vivo studies of the anti-microbial activity of Gm have been published. Rossi et al investigated the efficacy of Gm against disseminated and vaginal candidiasis in mice infected with the clinical strain of C. albicans (isolate 78) [ 34 ]. In both types of infections, Gm effectively reduced fungal burden compared to the control group, and did so at lower concentrations than fluoconazole (a commonly used anti-fungal agent to treat yeast infections in humans and animals).…”