Antimicrobial effects of XF drugs against Candida albicans and its biofilms.
Antimicrobial effects of XF drugs against Candida albicans and its biofilms.
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DOI：
10.3389/ffunb.2023.1225647
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发表时间：
2023
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与治疗细菌感染的抗生素相比，抗真菌药物的数量有限。这是由于几个因素，包括在不破坏宿主细胞的情况下寻找针对真菌细胞的合适的抗真菌药物的困难，以及与细菌引起的真菌感染相比，真菌感染的诊断率降低。治疗真菌感染的问题因人类真菌病原体中抗真菌耐药性的发生率增加而加剧。三种XF药物(XF-73、XF-70和DPD-207)以前显示出固有的杀菌作用和对微生物耐药的低倾向，其中XF-73和XF-70具有第二种光激活作用机制[称为光动力疗法(PDT)]。为了扩大抗真菌药物的范围，本研究通过两种作用机制评估了XF药物在浮游和生物膜培养中对六种真菌病原体白色念珠菌的体外活性。此外，本研究在一个重组的人类口腔上皮模型中检测了XF药物治疗对白色念珠菌生物膜的影响。白念珠菌对XF-73和XF-70均敏感，最低抑菌浓度(MIC)在0.25~2µg/mL之间，DPD-207的最低抑菌浓度(MIC)在4~16µg/mL之间，而DPD-207的最低抑菌浓度(MIC)较弱，光激活不能提高这些MIC。在测试的XF药物浓度下，没有报告完全消除生物被膜。然而，XF药物处理后生物膜中白色念珠菌细胞的活染色和死亡染色表明，XF-73和XF-70对大多数测试的生物被膜具有活性；同样，光激活不能增强抗生物被膜的活性。念珠菌生物被膜对DPD-207的抗性较强，杀菌效果在256微克/毫升以下。XF-73和XF-70减少了白色念珠菌生物膜对重组人口腔上皮(RHOE)的渗透，导致的损害(通过减少乳酸脱氢酶释放来确定)比未经处理的生物膜更少。总体而言，这些结果突出了XF药物作为治疗由白色念珠菌引起的局部感染的新药的潜力。XF药物作为抗真菌药物的开发值得进一步研究，特别是对XF-73和XF-70。
Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action [known as photodynamic therapy (PDT)]. In an effort to expand the repertoire of antifungal agents, this research assessed the in vitro activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen Candida albicans in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of C. albicans in a reconstituted human oral epithelium model. All C. albicans strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of C. albicans cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most Candida biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity. Candida biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of C. albicans biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.