Division of Biological Sciences, The University of Montana, Missoula, MT 59812, USA.
Int J Antimicrob Agents. 2010 Oct;36(4):380-2. doi: 10.1016/j.ijantimicag.2010.05.017.
Coxiella burnetii is the bacterial agent of Q fever in humans. Acute Q fever generally manifests as a flu-like illness and is typically self-resolving. In contrast, chronic Q fever usually presents with endocarditis and is often life-threatening without appropriate antimicrobial therapy. Unfortunately, available options for the successful treatment of chronic Q fever are both limited and protracted (>18 months). Pentamidine, an RNA splice inhibitor used to treat fungal and protozoal infections, was shown to reduce intracellular growth of Coxiella by ca. 73% at a concentration of 1 microM (ca. 0.6 microg/mL) compared with untreated controls, with no detectable toxic effects on host cells. Bacterial targets of pentamidine include Cbu.L1917 and Cbu.L1951, two group I introns that disrupt the 23S rRNA gene of Coxiella, as demonstrated by the drug's ability to inhibit intron RNA splicing in vitro. Since both introns are highly conserved amongst all eight genotypes of the pathogen, pentamidine is predicted to be efficacious against numerous strains of C. burnetii. To our knowledge, this is the first report describing antibacterial activity for this antifungal/antiprotozoal agent.
贝那普利是人类 Q 热的细菌剂。急性 Q 热通常表现为流感样疾病，通常自行缓解。相比之下，慢性 Q 热通常表现为心内膜炎，如果没有适当的抗菌治疗，通常是致命的。不幸的是，成功治疗慢性 Q 热的选择既有限又漫长（>18 个月）。戊二脒，一种用于治疗真菌和原生动物感染的 RNA 剪接抑制剂，在 1μM（约 0.6μg/mL）的浓度下，与未处理的对照相比，可将细胞内的柯克斯体生长减少约 73%，对宿主细胞没有检测到毒性作用。戊二脒的细菌靶标包括 Cbu.L1917 和 Cbu.L1951，这两个是 I 组内含子，可破坏柯克斯体的 23S rRNA 基因，这是由于药物在体外抑制内含子 RNA 剪接的能力。由于这两个内含子在病原体的所有八个基因型中高度保守，戊二脒预计对许多种 C. burnetii 菌株有效。据我们所知，这是第一个描述这种抗真菌/抗原生动物药物的抗菌活性的报告。
