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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Prates, Renato A. [1] ; Kato, Ilka T. [1] ; Ribeiro, Martha S. [1] ; Tegos, George P. [2, 3, 4] ; Hamblin, Michael R. [2, 3, 5]
Total Authors: 5
[1] IPEN CNEN SP, Ctr Lasers & Applicat, BR-05508000 Sao Paulo - Brazil
[2] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 - USA
[3] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 - USA
[4] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 - USA
[5] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 - USA
Total Affiliations: 5
Document type: Journal article
Source: Journal of Antimicrobial Chemotherapy; v. 66, n. 7, p. 1525-1532, JUL 2011.
Web of Science Citations: 52

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 INF(271), 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. (AU)

FAPESP's process: 10/13313-9 - Development of methodologies for photodynamic therapy applications on fungal infections
Grantee:Martha Simões Ribeiro
Support type: Regular Research Grants