Department of Parasitology, University of São Paulo, São Paulo, SP, Brazil.
BMC Microbiol. 2012 Mar 6;12:28. doi: 10.1186/1471-2180-12-28.
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.
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.
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.
抗菌肽存在于动物、植物和微生物中，在先天免疫反应中发挥着重要作用。Gomesin 是一种从蜘蛛 Acanthoscurria gomesiana 的血细胞中纯化的阳离子抗菌肽。它对细菌、真菌、原生动物和肿瘤细胞具有广谱活性。白色念珠菌是一种共生酵母，是人类微生物群的一部分。然而，在免疫功能低下的患者中，这种真菌可能会导致皮肤、粘膜或全身感染。这种真菌感染的典型治疗包括三大类抗真菌药物：多烯类、唑类和棘白菌素类；然而，这些药物的耐药性经常被报道。随着对常规抗生素具有耐药性的微生物的出现，开发治疗念珠菌病的替代方法很重要。在这项研究中，我们评估了 gomesin 治疗全身性和阴道念珠菌病的疗效及其毒性和生物分布。
gomesin 治疗有效降低了感染小鼠肾脏、脾脏、肝脏和阴道中的白色念珠菌。用锝-99m 标记的 gomesin 的生物分布表明，该肽被捕获在肾脏、脾脏和肝脏中。感染小鼠中检测到 TNF-α、IFN-γ 和 IL-6 的产量增加，表明其具有免疫调节活性。此外，用 gomesin 和氟康唑治疗后的免疫抑制和白色念珠菌感染的小鼠存活率增加。gomesin 的全身给药对小鼠也没有毒性。
gomesin 对实验性白色念珠菌感染有效。它可单独或与氟康唑联合用于治疗念珠菌病。gomesin 的作用机制尚不完全清楚，但我们假设该肽通过破坏酵母膜的通透性导致酵母死亡和/或释放酵母抗原，从而触发宿主对感染的免疫反应。因此，本研究提供的数据增强了 gomesin 作为人类和动物治疗性抗真菌剂的潜力。
