Pentamidine inhibits Coxiella burnetii growth and 23S rRNA intron splicing in vitro.

Pentamidine inhibits Coxiella burnetii growth and 23S rRNA intron splicing in vitro.
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Pentamidine 在体外抑制伯氏柯克斯体生长和 23S rRNA 内含子剪接。

DOI:
10.1016/j.ijantimicag.2010.05.017
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发表时间:
2010
影响因子:
10.8
通讯作者:
Raghavan,Rahul
Raghavan,Rahul
中科院分区:
医学2区
文献类型:
--
作者:
Minnick,MichaelF;Hicks,LindaD;Battisti,JamesM;Raghavan,Rahul

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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 1μM (ca. 0.6μg/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.