Antifungal Activity and Mode of Action of Miltefosine Against Clinical Isolates of Candida krusei
Antifungal Activity and Mode of Action of Miltefosine Against Clinical Isolates of Candida krusei
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PE-PGRS31-S100A9 相互作用通过调节 NF-κB-TNF-α 信号传导和花生四烯酸代谢促进巨噬细胞中分枝杆菌的存活
DOI：
10.3389/fmicb.2020.00854
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发表时间：
2020-05
影响因子：
5.2
通讯作者：
Ying Chunmei
中科院分区：
文献类型：
--
作者：
Wu Yongqin;Wu Mengying;Gao Jing;Ying Chunmei
克柔念珠菌引起医学专业人员的关注，主要是因为其对氟康唑的内在耐药性和治疗克柔念珠菌的药物有限。克柔氏外阴阴道念珠菌病米替福新在体内外均具有良好的抗真菌活性。在这里，我们确定了57个临床C。krusei菌株，并评估米替福新对念珠菌的抗真菌活性。krusei。所有分离株均对伏立康唑和伊曲康唑敏感，而1.8%的分离株对阿替霉素B为非野生型表型。相比之下，米替福新对所有C.具有杀真菌活性的克柔氏菌分离物。棋盘试验表明，在25%的试验药物C中观察到米替福新与阿替霉素B组合的协同作用。krusei分离株和18.8%的测试的预形成的生物膜，而米替福新与氟康唑组合显示出对所有测试的嗜酸性分离株的无关的相互作用。微量肉汤稀释法中山梨醇的存在不影响米替福新对念珠菌的MIC值。krusei，但麦角甾醇的存在增加了MIC值。观察到用米替福新处理的细胞中细胞含量的可见变化。我们发现，米替福新处理的细胞在PI染色下显示出细胞活力降低和染色质凝聚，这表明米替福新可能诱导C. krusei。结论：米替福新具有较好的抗C. Krusei通过结合细胞膜中的麦角固醇并诱导细胞凋亡来分离和发挥其杀真菌作用。
Candida krusei attracts attention from medical professionals mainly for its intrinsic resistance to fluconazole and the limited number of drugs available to treat C. krusei vulvovaginal candidiasis. Miltefosine was demonstrated to have good antifungal activity both in vitro and in vivo. Here, we determined the susceptibility profiles of 57 clinical C. krusei isolates from vulvovaginal candidiasis patients and assessed the antifungal activity of miltefosine against C. krusei. All isolates were susceptible to voriconazole and itraconazole, whereas 1.8% of the isolates were of non-wild-type phenotype to amphotericin B. In contrast, miltefosine showed low MICs against all C. krusei isolates with fungicidal activity. The checkerboard assay showed that the synergistic effect of miltefosine in combination with amphotericin B was observed in 25% of the tested planktonic C. krusei isolates and 18.8% of the tested preformed biofilms, whereas miltefosine in combination with fluconazole showed indifferent interaction for all tested planktonic isolates. The presence of sorbitol in the broth microdilution assay did not influence the MIC values of miltefosine against C. krusei, but the presence of ergosterol increased the MIC values. Visible changes in cell content in cells treated with miltefosine were observed. We found that cells treated with miltefosine showed decreased cell viability and chromatin condensation under PI staining, which indicates that miltefosine may induce apoptosis-like cell death in C. krusei. In conclusion, we found miltefosine has a good activity against C. krusei isolates and exerts its fungicidal effect by binding to ergosterol in the cell membrane and inducing apoptosis.
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DOI：
10.1016/j.ijantimicag.2016.07.022
发表时间：
2016-11
影响因子：
10.8
作者：
T. Vila;K. Ishida;S. Seabra;S. Rozental
通讯作者：
T. Vila;K. Ishida;S. Seabra;S. Rozental
影响因子：
4.9
作者：
C. Spadari;T. Vila;S. Rozental;K. Ishida
通讯作者：
C. Spadari;T. Vila;S. Rozental;K. Ishida
影响因子：
3.8
作者：
Pereira, Jozinete Vieira;Freires, Irlan Almeida;Rosalen, Pedro Luiz
通讯作者：
Rosalen, Pedro Luiz
影响因子：
9.4
作者：
Pfaller, M. A.;Diekema, D. J.;Veselov, A.
通讯作者：
Veselov, A.
影响因子：
3.8
作者：
Wasunna M;Njenga S;Balasegaram M;Alexander N;Omollo R;Edwards T;Dorlo TP;Musa B;Ali MH;Elamin MY;Kirigi G;Juma R;Kip AE;Schoone GJ;Hailu A;Olobo J;Ellis S;Kimutai R;Wells S;Khalil EA;Strub Wourgaft N;Alves F;Musa A
通讯作者：
Musa A