Influence of multidrug efflux systems on methylene blue-mediated photodynamic inactivation of Candida albicans

Renato A. Prates, Ilka T. Kato, Martha S. Ribeiro, George P. Tegos, Michael R. Hamblin

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Objectives: To investigate whether the major fungal multidrug efflux systems (MESs) affect the efficiency of methylene blue (MB)-mediated antimicrobial photodynamic inactivation (APDI) in pathogenic fungi and test specific inhibitors of these efflux systems to potentiate APDI. Methods: Candida albicans wild-type and mutants that overexpressed two classes of MESs [ATP-binding cassette (ABC) and major facilitator superfamily (MFS)] were tested for APDI using MB as the photosensitizer with and without addition of MES inhibitors. The uptake and cytoplasm localization of photosensitizer were achieved using laser confocal microscopy. Results: ABC MES overexpression reduced MB accumulation and APDI killing more than MFS MES overexpression. Furthermore, by combining MB APDI with the ABC inhibitor verapamil, fungal killing and MB uptake were potentiated, while by combining MB APDI with the MFS inhibitor INF271, fungal killing and MB uptake were inhibited. This latter surprising finding may be explained by the hypothesis that the MFS channel can also serve as an uptake mechanism for MB. Conclusions: The ABC pumps are directly implicated in MB efflux from the cell cytoplasm. Both the influx and efflux of MB may be regulated by MFS systems, and blocking this gate before incubation with MB can decrease the uptake and APDI effects. An ABC inhibitor could be usefully combined with MB APDI for treating C. albicans infections.

Original languageEnglish
Article numberdkr160
Pages (from-to)1525-1532
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume66
Issue number7
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Keywords

  • ABC transporters
  • Major facilitator superfamily
  • Photodynamic therapy
  • Photosensitizer
  • Verapamil

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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