Cagnacci Simone, Grasso Rachele, Marchese Anna, Corvò Renzo, Debbia Eugenio, Rossi Lorenzo
Institute of Microbiology "C.A Romanzi", Department DISCAT, University of Genoa, Largo Rosanna Benzi, 10, 16132, Genoa, Italy.
Open Microbiol J. 2008;2:66-73. doi: 10.2174/1874285800802010066. Epub 2008 May 23.
The virulence of C. albicans is associated with the transitional evolution from yeast to filamentous forms. We were interested in the effects amphotericin B (AMB), ketoconazole (KTC) and gamma-radiations might have on these broadly defined phenotypes as determined by the CFU procedure. By using collagen gel as the 3-dimensional support of cell culture, diverse experimental conditions were contemplated in order to modulate the differentiation of Candida during sessile and planktonic growth. These conditions included the co-culture with human epithelial and endothelial cells and treatment with farnesol, tyrosol and conditioned medium from P. aeruginosa. The overall results were as follows: 1) The survival of Candida was inhibited by the exposure to gamma-radiations, but only after the organism was induced to progress into excess filamentation, while in normal growth conditions it proved to be radioresistant; 2) AMB inhibited the growth of yeast forms, while KTC was specifically toxic to filamentous forms and 3) the combined treatment of filamentous Candida with KTC and gamma-radiations resulted in the synergistic inhibition of the organism. These findings indicate that both the radiosensitivity of C. albicans and its response to the synergistic effects of gamma-radiations and KTC are filamentation-dependent pharmacological processes.
白色念珠菌的毒力与从酵母形态到丝状形态的转变进化有关。我们感兴趣的是两性霉素B（AMB）、酮康唑（KTC）和γ射线对这些通过菌落形成单位（CFU）程序确定的广义表型可能产生的影响。通过使用胶原凝胶作为细胞培养的三维支持物，考虑了各种实验条件，以调节念珠菌在固着生长和浮游生长过程中的分化。这些条件包括与人上皮细胞和内皮细胞共培养，以及用法尼醇、酪醇和铜绿假单胞菌的条件培养基处理。总体结果如下：1）念珠菌的存活受到γ射线照射的抑制，但仅在该生物体被诱导过度丝状化之后，而在正常生长条件下它被证明具有抗辐射性；2）AMB抑制酵母形态的生长，而KTC对丝状形态具有特异性毒性；3）丝状念珠菌与KTC和γ射线的联合处理导致对该生物体的协同抑制。这些发现表明，白色念珠菌的放射敏感性及其对γ射线和KTC协同作用的反应都是丝状化依赖性的药理学过程。
