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抗真菌多烯类药物对白色念珠菌和光滑念珠菌体外黏附人上皮细胞的影响。

Influence of antifungal polyenes on the adhesion of Candida albicans and Candida glabrata to human epithelial cells in vitro.

作者信息

Dorocka-Bobkowska B, Konopka K, Düzgüneş N

机构信息

Department of Microbiology, School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.

出版信息

Arch Oral Biol. 2003 Dec;48(12):805-14. doi: 10.1016/s0003-9969(03)00174-2.

Abstract

Candidal adherence to mucosal surfaces is considered as the first step in the pathogenesis of oral candidiasis. We examined the effect of antifungal polyenes, amphotericin B, nystatin and natamycin, at sublethal and minimum inhibitory concentrations (MICs) on the adherence of Candida albicans and Candida glabrata to HeLa cervical carcinoma and HSC-3 oral squamous cell carcinoma cells. A total of six oral Candida isolates were used throughout the study. Two Candida strains, C. albicans (44990) and C. glabrata (MYA-275) were obtained from ATCC. Four Candida strains, C. albicans 19 and 24 and C. glabrata 15 and 21, were isolated from patients with documented Candida-associated denture stomatitis. Cells were either incubated with Candida in the presence of the drug, or pre-incubated with yeasts and exposed subsequently to the drug. In the drug-free controls, the mean number of C. albicans yeasts associated with HeLa cells obtained from all experiments (130.1+/-10.1 yeasts/mm(2)) was significantly greater than that for HSC-3 cells (114.7+/-10.1 yeasts/mm(2); P<0.025). For C. glabrata, the mean adherence to HeLa and HSC-3 cells was 84.4+/-5.5 and 84.4+/-3.3 yeasts/mm(2), respectively, and these values were not statistically different (P>0.4). Candidal adherence was significantly reduced when the tested polyenes were present during the "adherence phase". The obtained values were significantly different from the controls, except for the effect of nystatin at the MIC on the adherence of C. glabrata strain MYA-275 to HeLa cells (P<0.375). Amphotericin B had the highest effect against both Candida species, reducing adherence by approximately 50 and approximately 60%, at the MIC and sublethal concentrations, respectively. The susceptibility of cell-associated Candida to polyenes was decreased markedly and the treatment did not result in significant detachment of adherent yeasts. The reduction in adherence was between 2 and 10%, when compared to the drug-free controls. These findings suggest that sub-therapeutic levels of polyenes that are likely to persist in the oral cavity following topical treatment may modulate candidal colonization when present during the "adherence phase".

摘要

念珠菌对黏膜表面的黏附被认为是口腔念珠菌病发病机制的第一步。我们检测了抗真菌多烯类药物两性霉素B、制霉菌素和游霉素在亚致死浓度和最小抑菌浓度(MIC)下对白色念珠菌和光滑念珠菌黏附HeLa宫颈癌细胞和HSC - 3口腔鳞状癌细胞的影响。在整个研究中总共使用了6株口腔念珠菌分离株。两株念珠菌菌株,白色念珠菌(44990)和光滑念珠菌(MYA - 275)购自美国典型培养物保藏中心(ATCC)。另外4株念珠菌菌株,白色念珠菌19和24以及光滑念珠菌15和21,是从患有确诊念珠菌相关性义齿性口炎的患者中分离得到的。细胞要么在药物存在的情况下与念珠菌一起孵育,要么先与酵母预孵育,随后再接触药物。在无药物对照中,从所有实验中获得的与HeLa细胞相关的白色念珠菌酵母的平均数量(130.1±10.1个酵母/mm²)显著高于与HSC - 3细胞相关的数量(114.7±10.1个酵母/mm²;P<0.025)。对于光滑念珠菌,其对HeLa细胞和HSC - 3细胞的平均黏附数分别为84.4±5.5和84.4±3.3个酵母/mm²,这些值无统计学差异(P>0.4)。当在“黏附阶段”存在受试多烯类药物时,念珠菌的黏附显著降低。除了制霉菌素在MIC浓度下对光滑念珠菌菌株MYA - 275黏附HeLa细胞的影响外(P<0.375),所获得的值与对照有显著差异。两性霉素B对两种念珠菌的作用最强,在MIC浓度和亚致死浓度下分别使黏附降低约50%和约60%。与细胞相关的念珠菌对多烯类药物的敏感性显著降低,并且该处理并未导致黏附的酵母显著脱落。与无药物对照相比,黏附降低了2%至10%。这些发现表明,局部治疗后可能在口腔中持续存在的亚治疗水平的多烯类药物在“黏附阶段”存在时可能调节念珠菌的定植。

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