Nobile Clarissa J, Ennis Craig L, Hartooni Nairi, Johnson Alexander D, Lohse Matthew B
Department of Molecular and Cell Biology, School of Natural Sciences, University of California-Merced, Merced, CA 95343, USA.
Quantitative and Systems Biology Graduate Program, University of California-Merced, Merced, CA 95343, USA.
Microorganisms. 2020 May 18;8(5):756. doi: 10.3390/microorganisms8050756.
Biofilms formed by the human fungal pathogen are naturally resistant to many of the antifungal agents commonly used in the clinic. We screened a library containing 1600 clinically tested drug compounds to identify compounds that inhibit biofilm formation. The compounds that emerged from the initial screen were validated in a secondary screen and then tested for (1) their abilities to disrupt mature biofilms and (2) for synergistic interactions with representatives of the three antifungal agents most commonly prescribed to treat infections, fluconazole, amphotericin B, and caspofungin. Twenty compounds had antibiofilm activity in at least one of the secondary assays and several affected biofilms but, at the same concentration, had little or no effect on planktonic (suspension) growth of . Two calcium channel blockers, a selective serotonin reuptake inhibitor, and an azole-based proton pump inhibitor were among the hits, suggesting that members of these three classes of drugs or their derivatives may be useful for treating biofilm infections.
由人类真菌病原体形成的生物膜对临床上常用的许多抗真菌药物具有天然抗性。我们筛选了一个包含1600种经临床测试的药物化合物的文库,以鉴定抑制生物膜形成的化合物。从初步筛选中脱颖而出的化合物在二次筛选中得到验证,然后测试它们(1)破坏成熟生物膜的能力,以及(2)与治疗感染最常用的三种抗真菌药物(氟康唑、两性霉素B和卡泊芬净)的代表药物的协同相互作用。二十种化合物在至少一项二次试验中具有抗生物膜活性,有几种对生物膜有影响,但在相同浓度下,对该病原体的浮游(悬浮)生长几乎没有影响或没有影响。其中的热门药物包括两种钙通道阻滞剂、一种选择性5-羟色胺再摄取抑制剂和一种基于唑类的质子泵抑制剂,这表明这三类药物的成员或其衍生物可能对治疗该病原体的生物膜感染有用。