Pereira Jorge Augusto Leão, Moraes Lienne Silveira de, Sena Chubert Bernardo Castro de, Nascimento José Luiz Martins do, Rodrigues Ana Paula D, Silva Silvia Helena Marques da, Silva Edilene O
Laboratory of Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil.
National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro 21040-900, RJ, Brazil.
Pathogens. 2022 Aug 17;11(8):925. doi: 10.3390/pathogens11080925.
Chromoblastomycosis (CBM) is a chronic human subcutaneous mycosis caused by various aetiologic agents. CBM does not have an established treatment but may be managed using antifungal agents, surgical removal of the lesions, or cryotherapy. Kojic acid (KA), a known tyrosinase inhibitor with a variety of biological actions, including fungistatic action against the fungus Cryptococcus neoformans, mediated by inhibiting melanin production, seems to be an alternative to improve the treatment of CBM. The aim of the present study was to analyze the action of KA against the pathogenic fungus Fonsecaea sp., an aetiological agent of CBM. The fungal culture was incubated with KA, and the amount of melanin was assessed, followed by cytochemical detection. Subsequently, the samples were analyzed by light microscopy, transmission and scanning electron microscopy. Culture analysis revealed that 100 g/mL KA significantly decreased the melanization of the fungus and the exocytosis of melanin into the culture supernatant. Additionally, KA induced less growth of biofilm formation and intense disruption of the cell wall, and decreased the number of melanin-containing vesicles in the culture supernatant. Finally, KA inhibited fungal filamentation in culture and the subsequent phagocytosis process. Thus, KA may be a promising substance to help in the treatment of CBM.
着色芽生菌病（CBM）是一种由多种病原体引起的慢性人类皮下真菌病。CBM尚无既定的治疗方法，但可使用抗真菌药物、手术切除病灶或冷冻疗法进行处理。曲酸（KA）是一种已知的酪氨酸酶抑制剂，具有多种生物学作用，包括通过抑制黑色素生成对新型隐球菌产生抑菌作用，似乎是改善CBM治疗的一种替代方法。本研究的目的是分析KA对CBM病原体真菌裴氏着色霉的作用。将真菌培养物与KA一起孵育，评估黑色素的含量，随后进行细胞化学检测。随后，通过光学显微镜、透射电子显微镜和扫描电子显微镜对样本进行分析。培养分析表明，100μg/mL的KA显著降低了真菌的黑色素化以及黑色素向培养上清液中的胞吐作用。此外，KA抑制生物膜形成的生长并强烈破坏细胞壁，并减少培养上清液中含黑色素囊泡的数量。最后，KA抑制培养物中的真菌丝状化及随后的吞噬过程。因此，KA可能是有助于治疗CBM的一种有前景的物质。
