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

Abstract:

: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.

authors

Minnick MF,Hicks LD,Battisti JM,Raghavan R

doi

10.1016/j.ijantimicag.2010.05.017

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

380-2

issue

4

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(10)00236-0

journal_volume

36

pub_type

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