| Autor: |
Mukherjee, Pranab K., Mohamed, Sotohy, Chandra, Jyotsna, Kuhn, Duncan, Liu, Shuqing, Antar, Omar S., Munyon, Ryan, Mitchell, Aaron P., Andes, David, Chance, Mark R., Rouabhia, Mahmoud, Ghannoum, Mahmoud A. |
| Zdroj: |
Infection and Immunity; July 2006, Vol. 74 Issue: 7 p3804-3816, 13p |
| Abstrakt: |
ABSTRACTCandidabiofilms formed on indwelling medical devices are increasingly associated with severe infections. In this study, we used proteomics and Western and Northern blotting analyses to demonstrate that alcohol dehydrogenase (ADH) is downregulated in Candidabiofilms. Disruption of ADH1significantly (P= 0.0046) enhanced the ability of Candida albicansto form biofilm. Confocal scanning laser microscopy showed that the adh1mutant formed thicker biofilm than the parent strain (210 μm and 140 μm, respectively). These observations were extended to an engineered human oral mucosa and an in vivo rat model of catheter-associated biofilm. Inhibition of CandidaADH enzyme using disulfiram and 4-methylpyrazole resulted in thicker biofilm (P< 0.05). Moreover, biofilms formed by the adh1mutant strain produced significantly smaller amounts of ethanol, but larger amounts of acetaldehyde, than biofilms formed by the parent and revertant strains (P< 0.0001), demonstrating that the effect of Adh1p on biofilm formation is mediated by its enzymatic activity. Furthermore, we found that 10% ethanol significantly inhibited biofilm formation in vitro, with complete inhibition of biofilm formation at ethanol concentrations of ≥20%. Similarly, using a clinically relevant rabbit model of catheter-associated biofilm, we found that ethanol treatment inhibited biofilm formation by C. albicansin vivo (P< 0.05) but not by Staphylococcusspp. (P> 0.05), indicating that ethanol specifically inhibits Candidabiofilm formation. Taken together, our studies revealed that Adh1p contributes to the ability of C. albicansto form biofilms in vitro and in vivo and that the protein restricts biofilm formation through an ethanol-dependent mechanism. These results are clinically relevant and may suggest novel antibiofilm treatment strategies. |
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