期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 36, 期 4, 页码 380-382出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2010.05.017
关键词
Coxiella; Pentamidine; Group I intron; RNA splicing
资金
- NIH [R21 AI078125]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI078125] Funding Source: NIH RePORTER
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 mu M (ca. 0.6 mu g/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. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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