Overcoming the antifungal drug resistance of biofilms on dental acrylic

Candida;albicans;antifungal;resistance;biofilm;dental

Newsham-West, Kathryn J ; Cannon, Richard ; Niimi, Kyoko

University of Otago

关键词: Candida;    albicans;    antifungal;    resistance;    biofilm;    dental;   

Others  :  https://ourarchive.otago.ac.nz/bitstream/10523/4354/1/Newsham-WestKathrynJDClinDent.pdf

美国|英语

来源: Otago University Research Archive

【 摘 要 】

IntroductionRC21v3 is an octapeptide derivative that inhibits the drug efflux pump that confers azole resistance on the yeast Candida albicans -an opportunistic pathogen that can cause denture stomatitis. C. albicans often forms biofilms on oral surfaces including denture prostheses, and biofilm cells are more drug resistant than planktonic cells growing as a suspension in liquid medium.AimThe objective of this research was to determine whether RC21v3 acts synergistically with fluconazole (FLC) to inhibit the growth of C. albicans cells in planktonic cultures and during growth as a biofilm.MethodsMinimum growth inhibition concentration (MIC) assays were undertaken to measure the inhibitory effect of FLC and RC21v3 on C. albicans cells growing as planktonic cultures. Checkerboard MIC assays were used to measure the effect of combinations of FLC with RC21v3 on both planktonic and biofilm growth. The inhibition of C. albicans biofilm growth on denture acrylic was measured using crystal violet staining of biofilm cells. The effect of FLC and/or RC21v3 on biofilm structure was investigated using confocal microscopy.ResultsCheckerboard MIC assays showed that RC21v3 acted synergistically with FLC to inhibit the planktonic growth of three C. albicans strains: ATCC 10261 andMML610 which are FLC-susceptible, and MML611 which is FLC-resistant. In addition, the combination of RC21v3 with FLC in growth assays resulted in FLC becoming fungicidal to all three strains. A novel dental acrylic biofilm model was developed. As it demonstrated reproducible growth of C. albicans, it could be used to measure biofilm growth inhibition. FLC inhibited the growth of C. albicans biofilms and checkerboard assays showed that RC21v3 acted synergistically to reduce the growth of ATCC10261 biofilms.ConclusionThis is the first demonstration that RC21v3 can chemosensitize C. albicans biofilms to fluconazole, and so may be of use in treatment of patients with FLC-resistant biofilms on denture surfaces.