Specialized Medical Mycology Center, Postgraduate Program in Medical Microbiology, Department of Pathology and Legal Medicine, Federal University of Ceará. Rua Cel. Nunes de Melo, 1315 - Rodolfo Teófilo - CEP: 60430-275, Fortaleza, Ceará, Brazil.
Postgraduate Program in Veterinary Sciences, College of Veterinary, State University of Ceará. Av. Dr. Silas Munguba, 1700, Campus do Itaperi, CEP: 60714-903, Fortaleza, Ceará, Brazil.
Med Mycol. 2021 Jul 14;59(8):793-801. doi: 10.1093/mmy/myab001.
Invasive fungal infections (IFIs) are important worldwide health problem, affecting the growing population of immunocompromised patients. Although the majority of IFIs are caused by Candida spp., other fungal species have been increasingly recognized as relevant opportunistic pathogens. Trichosporon spp. are members of skin and gut human microbiota. Since 1980's, invasive trichosporonosis has been considered a significant cause of fungemia in patients with hematological malignancies. As prolonged antibiotic therapy is an important risk factor for IFIs, the present study investigated if vancomycin enhances growth and virulence of Trichosporon. Vancomycin was tested against T. inkin (n = 6) and T. asahii (n = 6) clinical strains. Planktonic cells were evaluated for their metabolic activity and virulence against Caenorhabditis elegans. Biofilms were evaluated for metabolic activity, biomass production, amphotericin B tolerance, induction of persister cells, and ultrastructure. Vancomycin stimulated planktonic growth of Trichosporon spp., increased tolerance to AMB, and potentiates virulence against C. elegans. Vancomycin stimulated growth (metabolic activity and biomass) of Trichosporon spp. biofilms during all stages of development. The antibiotic increased the number of persister cells inside Trichosporon biofilms. These cells showed higher tolerance to AMB than persister cells from VAN-free biofilms. Microscopic analysis showed that VAN increased production of extracellular matrix and cells in T. inkin and T. asahii biofilms. These results suggest that antibiotic exposure may have a direct impact on the pathophysiology of opportunistic trichosporonosis in patients at risk.
This study showed that the vancomycin stimulated Trichosporon growth, induced morphological and physiological changes on their biofilms, and also enhanced their in vivo virulence. Although speculative, the stimulatory effect of vancomycin on fungal cells should be considered in a clinical scenario.
侵袭性真菌感染（IFI）是一个全球性的重要健康问题，影响着越来越多的免疫功能低下患者。虽然大多数IFI 是由念珠菌属引起的，但其他真菌物种已被越来越多地认为是相关的机会性病原体。毛孢子菌属是皮肤和肠道人类微生物群的成员。自 20 世纪 80 年代以来，侵袭性毛孢子菌病已被认为是血液恶性肿瘤患者菌血症的重要原因。由于长期使用抗生素治疗是 IFI 的一个重要危险因素，本研究调查了万古霉素是否会增强毛孢子菌的生长和毒力。对 T. inkin（n=6）和 T. asahii（n=6）临床株进行了万古霉素测试。评估浮游细胞的代谢活性和对秀丽隐杆线虫的毒力。评估生物膜的代谢活性、生物量产生、两性霉素 B 耐受性、诱导持久细胞和超微结构。万古霉素刺激毛孢子菌属浮游细胞的生长，增加对两性霉素 B 的耐受性，并增强对秀丽隐杆线虫的毒力。万古霉素刺激毛孢子菌属生物膜的生长（代谢活性和生物量）在所有发育阶段。抗生素增加了毛孢子菌生物膜内的持久细胞数量。与无 VAN 生物膜中的持久细胞相比，这些细胞对两性霉素 B 的耐受性更高。显微镜分析显示，VAN 增加了 T. inkin 和 T. asahii 生物膜中细胞外基质和细胞的产生。这些结果表明，抗生素暴露可能对处于危险中的患者的机会性毛孢子菌病的病理生理学有直接影响。
本研究表明，万古霉素刺激了毛孢子菌的生长，诱导了其生物膜的形态和生理变化，并增强了其体内毒力。尽管推测性的，但在临床情况下应考虑万古霉素对真菌细胞的刺激作用。
