JAC Advance Access first published online on December 4, 2008
This version published online on December 18, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn486
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original research |
Antifungal mechanisms supporting boric acid therapy of Candida vaginitis
1 Burlo Garofolo, University of Trieste, Trieste, Italy 2 Department of University Research, Des Moines University, Des Moines, IA, USA 3 Department of Biochemistry and Nutrition, Des Moines University, Des Moines, IA, USA 4 Department of Pharmaceutical Science, Drake University, Des Moines, IA, USA
Received 13 June 2008; returned 4 August 2008; revised 24 September 2008; accepted 28 October 2008
* Corresponding author. Tel: +1-515-271-1559; Fax: +1-515-271-1644; E-mail: bryan.larsen{at}dmu.edu
Background: Boric acid is a commonly cited treatment for recurrent and resistant yeast vaginitis, but data about the extent and mechanism of its antifungal activity are lacking.
Objectives: The aim of this study was to use in vitro methods to understand the spectrum and mechanism of boric acid as a potential treatment for vaginal infection.
Methods: Yeast and bacterial isolates were tested by agar dilution to determine the intrinsic antimicrobial activity of boric acid. Established microbial physiology methods illuminated the mechanism of the action of boric acid against Candida albicans.
Results: C. albicans strains (including fluconazole-resistant strains) were inhibited at concentrations attainable intravaginally; as were bacteria. Broth dilution MICs were between 1563 and 6250 mg/L and boric acid proved fungistatic (also reflected by a decrease in CO2 generation); prolonged culture at 50 000 mg/L was fungicidal. Several organic acids in yeast nitrogen broth yielded a lower pH than equimolar boric acid and sodium borate but were less inhibitory. Cold or anaerobic incubation protected yeast at high boric acid concentrations. Cells maintained integrity for 6 h in boric acid at 37°C, but after 24 h modest intrusion of propidium iodide occurred; loss of plate count viability preceded uptake of vital stain. Growth at sub-MIC concentrations of boric acid decreased cellular ergosterol. The drug efflux pump CDR1 did not protect Candida as CDR1 expression was abrogated by boric acid. Boric acid interfered with the development of biofilm and hyphal transformation.
Conclusions: Boric acid is fungistatic to fungicidal depending on concentration and temperature. Inhibition of oxidative metabolism appears to be a key antifungal mechanism, but inhibition of virulence probably contributes to therapeutic efficacy in vivo.
Key Words: C. albicans , vaginal infections , antifungal activity , antifungal therapy
The original version was incorrect. It should have read ‘Francesco De Seta’ not ‘Francesco DeSeta’