Vipulanandan G, Herrera M, Wiederhold N P, Li X, Mintz J, Wickes B L, Kadosh D
1 Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
2 Department of Pathology and Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
J Dent Res. 2018 Jan;97(1):91-98. doi: 10.1177/0022034517729351. Epub 2017 Aug 29.
Oral infections caused by Candida species, the most commonly isolated human fungal pathogen, are frequently associated with biofilms. Although Candida albicans is the predominant organism found in patients with oral thrush, a biofilm infection, there is an increasing incidence of oral colonization and infections caused by non- albicans Candida species, including C. glabrata, C. dubliniensis, and C. tropicalis, which are frequently more resistant to antifungal treatment. While single-species Candida biofilms have been well studied, considerably less is known about the dynamics of mixed- Candida species biofilms and how these dynamics are altered by antifungal treatment. To address these questions, we developed a quantitative polymerase chain reaction-based approach to determine the precise species composition of mixed- Candida species biofilms formed by clinical isolates and laboratory strains in the presence and absence of clinically relevant concentrations of 3 commonly used antifungals: fluconazole, caspofungin, and amphotericin B. In monospecies biofilms, fluconazole exposure favored growth of C. glabrata and C. tropicalis, while caspofungin generally favored significant growth of all species to a varying degree. Fluconazole was not effective against preformed mixed- Candida species biofilms while amphotericin B was potent. As a general trend, in mixed- Candida species biofilms, C. albicans lost dominance in the presence of antifungals. Interestingly, presence in mixed versus monospecies biofilms reduced susceptibility to amphotericin B for C. tropicalis and C. glabrata. Overall, our data suggest that antifungal treatment favors the growth of specific non- albicans Candida species in mixed- Candida species biofilms.
念珠菌属引起的口腔感染是最常见的人类真菌病原体感染，常与生物膜相关。虽然白色念珠菌是口腔鹅口疮（一种生物膜感染）患者中发现的主要病原体，但非白色念珠菌属，包括光滑念珠菌、都柏林念珠菌和热带念珠菌引起的口腔定植和感染发生率正在上升，这些菌通常对抗真菌治疗更具抗性。虽然单一念珠菌属生物膜已得到充分研究，但对于混合念珠菌属生物膜的动态变化以及这些动态如何因抗真菌治疗而改变，人们了解得要少得多。为了解决这些问题，我们开发了一种基于定量聚合酶链反应的方法，以确定在存在和不存在临床相关浓度的3种常用抗真菌药物（氟康唑、卡泊芬净和两性霉素B）的情况下，由临床分离株和实验室菌株形成的混合念珠菌属生物膜的精确物种组成。在单一物种生物膜中，暴露于氟康唑有利于光滑念珠菌和热带念珠菌的生长，而卡泊芬净通常在不同程度上有利于所有物种的显著生长。氟康唑对预先形成的混合念珠菌属生物膜无效，而两性霉素B则有效。一般来说，在混合念珠菌属生物膜中，白色念珠菌在抗真菌药物存在的情况下失去优势地位。有趣的是，与单一物种生物膜相比，在混合生物膜中的热带念珠菌和光滑念珠菌对两性霉素B的敏感性降低。总体而言，我们的数据表明，抗真菌治疗有利于混合念珠菌属生物膜中特定非白色念珠菌属物种的生长。
