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.
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.
Authors: N A Romanova; L Y Brovko; L Moore; E Pometun; A P Savitsky; N N Ugarova; M W Griffiths Journal: Appl Environ Microbiol Date: 2003-11 Impact factor: 4.792
Authors: Tianhong Dai; Vida J Bil de Arce; George P Tegos; Michael R Hamblin Journal: Antimicrob Agents Chemother Date: 2011-09-19 Impact factor: 5.191
Authors: Letícia F M Dos Santos; Nathália B Melo; Marina L de Carli; Ana Carolina S C Mendes; Giulia Maria A C Bani; Liana M Verinaud; Eva Burger; Gabriel de Oliveira I Moraes; Alessandro A C Pereira; Maísa R L Brigagão; João Adolfo C Hanemann; Felipe F Sperandio Journal: Lasers Med Sci Date: 2017-03-27 Impact factor: 3.161
Authors: Domingo Mariano Adolfo Vera; Mark H Haynes; Anthony R Ball; Tianhong Dai; Christos Astrakas; Michael J Kelso; Michael R Hamblin; George P Tegos Journal: Photochem Photobiol Date: 2012-02-13 Impact factor: 3.421
Authors: Tyler G St Denis; Tianhong Dai; Leonid Izikson; Christos Astrakas; Richard Rox Anderson; Michael R Hamblin; George P Tegos Journal: Virulence Date: 2011-11-01 Impact factor: 5.882