背景:尽管经过适当的治疗,白色念珠菌尿路感染(UTI)的复发还是很常见的,作为常用的抗真菌剂,如氟康唑和氟胞嘧啶只是真菌抑制剂。改善念珠菌UTI的治疗,减少复发,需要了解白色念珠菌在含有最小抑制浓度(MIC)抗真菌剂的尿液中的长期代谢活性和存活率。
方法:我们监测了生存率,使用常规方法和等温微量热法(IMC),白色念珠菌对葡萄糖和蛋白质的代谢活性和消耗。我们还研究了死亡的念珠菌细胞对其活体细胞生长的影响。
结果:33天,在含有抗真菌药的样品中观察到弱活性,其中白色念珠菌的生长速率降低了48%,60%和88%,滞后增加到172小时,两性霉素168小时和6小时,氟胞嘧啶和氟康唑,分别。代谢活性峰与平板计数相对应,但与资源耗尽相比有所延迟。死细胞的存在促进了人工尿液中的生长,以相似的比例提高增长率并减少滞后。
结论:即使使用抗真菌治疗,白色念珠菌复发是可能的。存活细胞的低代谢活性导致再生和衣原体孢子形成,可能由自噬支持,这可能是复发的重要因素。
BACKGROUND: Relapse of Candida albicans urinary tract infection (UTI) is frequent despite appropriate treatment, as commonly used antifungals such fluconazole and flucytosine are only fungistatics. To improve treatment of Candida UTI and decrease relapses, understanding the long-term metabolic activity and survival of C. albicans in urine containing antifungals at minimal inhibitory concentration (MIC) is needed.
METHODS: we monitored the survival, metabolic activity and consumption of glucose and proteins by C. albicans using conventional methods and isothermal microcalorimetry (IMC). We also investigated the influence of dead Candida cells on the growth of their living counterparts.
RESULTS: For 33 days, weak activity was observed in samples containing antifungals in which C. albicans growth rate was reduced by 48%, 60% and 88%, and the lag increased to 172 h, 168 h and 6 h for amphotericin, flucytosine and fluconazole, respectively. The metabolic activity peaks corresponded to the plate counts but were delayed compared to the exhaustion of resources. The presence of dead cells promoted growth in artificial urine, increasing growth rate and reducing lag in similar proportions.
CONCLUSIONS: Even with antifungal treatment, C. albicans relapses are possible. The low metabolic activity of surviving cells leading to regrowth and chlamydospore formation possibly supported by autophagy are likely important factors in relapses.