title: Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesiana in the control of experimental candidiasis.
abstract: BACKGROUND
  Antimicrobial 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.
  
  
  RESULTS
  Treatment 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 mice.
  
  
  CONCLUSIONS
  Gomesin 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.
authors.affiliation: Department of Parasitology, University of São Paulo, São Paulo, SP, Brazil. sidaffre@icb.usp.br
authors.forename: Diego C
authors.initials: DC
authors.lastname: Rossi
authors.forename: Julian E
authors.initials: JE
authors.lastname: Muñoz
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Carvalho
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Belmonte
authors.forename: Bluma
authors.initials: B
authors.lastname: Faintuch
authors.forename: Primavera
authors.initials: P
authors.lastname: Borelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Taborda
authors.forename: Sirlei
authors.initials: S
authors.lastname: Daffre
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013112:Spiders / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C415987:gomesin; D007371:Interferon-gamma; D015725:Fluconazole