Inhibition of nucleic acid biosynthesis makes little difference to formation of amphotericin B-tolerant persisters in Candida albicans biofilm.
Inhibition of nucleic acid biosynthesis makes little difference to formation of amphotericin B-tolerant persisters in Candida albicans biofilm.
复制标题
核酸生物合成的抑制对于白色念珠菌生物膜中两性霉素 B 耐受性持续细胞的形成影响不大。
DOI：
10.1128/aac.03765-14
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发表时间：
2015
影响因子：
4.9
通讯作者：
Qi Qingguo
中科院分区：
文献类型：
--
作者：
Sun Jing;Liu Xiaohua;Jiang Guangshui;Qi Qingguo
白色念珠菌是生物被膜细胞的一个小亚群，在顽固性慢性念珠菌病中起主要作用；然而，白念珠菌外周形成的机制尚不清楚。持久者通常被描述为休眠、耐多药、不生长的细胞。持久细胞很难分离和研究，不仅因为它们在白色念珠菌生物膜中的水平很低，而且还因为它们的瞬时、可逆的表型。在本研究中，我们试图通过诱导白念珠菌细胞进入休眠状态来诱导持续体的形成。白念珠菌细胞用5-氟胞嘧啶(浮游细胞，0.8μg m l−1；生物膜细胞，1μg m l−1)在37℃处理6h，抑制核酸和蛋白质的合成。对8株白色念珠菌的生物被膜和浮游培养经两性霉素B(100μg ml−1作用24 h)和菌落形成单位(CFU)进行检测。无论有没有5-氟胞嘧啶处理的浮游培养物，都不含有持续体。在所有受试白色念珠菌菌株的生物膜中都发现了持久细胞，约占总种群的0.01-1.93%。然而，经5-氟胞嘧啶处理的白色念珠菌生物膜中的持续体水平并没有显著增加。这些结果表明，抑制核酸合成似乎不会增加白色念珠菌生物膜中两性霉素B耐药株的形成。
Candida albicans persisters constitute a small subpopulation of biofilm cells and play a major role in recalcitrant chronic candidiasis; however, the mechanism underlying persister formation remains unclear. Persisters are often described as dormant, multidrug-tolerant, nongrowing cells. Persister cells are difficult to isolate and study not only due to their low levels in C. albicans biofilms but also due to their transient, reversible phenotype. In this study, we tried to induce persister formation by inducing C. albicans cells into a dormant state. C. albicans cells were pretreated with 5-fluorocytosine (planktonic cells, 0.8 μg ml−1; biofilm cells, 1 μg ml−1) for 6 h at 37°C, which inhibits nucleic acid and protein synthesis. Biofilms and planktonic cultures of eight C. albicans strains were surveyed for persisters after amphotericin B treatment (100 μg ml−1for 24 h) and CFU assay. None of the planktonic cultures, with or without 5-fluorocytosine pretreatment, contained persisters. Persister cells were found in biofilms of all tested C. albicans strains, representing approximately 0.01 to 1.93% of the total population. However, the persister levels were not significantly increased in C. albicans biofilms pretreated with 5-fluorocytosine. These results suggest that inhibition of nucleic acid synthesis did not seem to increase the formation of amphotericin B-tolerant persisters in C. albicans biofilms.