J Med Microbiol VLA Conference September 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jmm.0.015784-0v1
59/2/149    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Al-Dhaheri, R. S.
Right arrow Articles by Douglas, L. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Al-Dhaheri, R. S.
Right arrow Articles by Douglas, L. J.
Agricola
Right arrow Articles by Al-Dhaheri, R. S.
Right arrow Articles by Douglas, L. J.
J Med Microbiol 59 (2010), 149-157; DOI: 10.1099/jmm.0.015784-0
© 2010 Society for General Microbiology
ISSN 0022-2615

Apoptosis in Candida biofilms exposed to amphotericin B

Rawya S. Al-Dhaheri and L. Julia Douglas

Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK

Correspondence
L. Julia Douglas
j.douglas{at}bio.gla.ac.uk

Received September 4, 2009
Accepted November 3, 2009

Candida biofilms are resistant to a range of antifungal agents in current clinical use. The basis of this drug resistance is not clear, but in some cases it could be due to the presence of a small number of drug-tolerant or persister cells. In this study, specific staining methods were used to investigate the existence of persisters and apoptosis in Candida biofilms subjected to different concentrations of amphotericin B. Fluorescein diacetate staining revealed the presence of persisters in biofilms of one of two strains of Candida albicans tested, and in biofilms of Candida krusei and Candida parapsilosis. Caspase activity, indicative of apoptosis, was detected with SR-FLICA and (aspartyl)2-rhodamine 110 fluorochrome-based staining reagents in all of these biofilms. The general inhibitor of mammalian caspases, Z-VAD-FMK, when used at a low concentration (2.5 µM), increased the viability of drug-treated biofilms up to 11.5-fold (P <0.001 %). Seven specific caspase inhibitors had different effects on C. albicans biofilm viability, but inhibitors of caspases-1, –9, –5, –3 and –2 all significantly increased cell survival (40-fold, 8-fold, 3.5-fold, 1.9-fold and 1.7-fold, respectively). However, histone deacetylase (HDA) inhibitors enhanced the activity of amphotericin B for biofilms of all three Candida species. Sodium butyrate and sodium valproate, for example, when added concurrently with amphotericin B, completely eliminated biofilm populations of C. albicans. Overall, our results demonstrate an apoptotic process in amphotericin-treated biofilms of three Candida species. They also indicate that HDA inhibitors can enhance the action of the drug and in some cases even eradicate persister subpopulations, suggesting that histone acetylation might activate apoptosis in these cells.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL J MED MICROBIOL MICROBIOLOGY J GEN VIROL ALL SGM JOURNALS
Copyright © 2010 Society for General Microbiology.