Abstract
Efficacy of five plant molecules against thirty three clinical isolates and two standard strains of C. albicans, differentially susceptible to fluconazole (FLC) is tested in this study. Effect on biofilm (adhesion, development and maturation) formation, morphogenesis and synergy with fluconazole (FLC) against a FLC resistant strain of Candida albicans ATCC 10231 is also evaluated. All the plant molecules tested were equally effective against isolates and strains of C. albicans (N = 35) tested in this study. Cinnamaldehyde was found most effective against planktonic growth followed by ocimene. Both the molecules exhibited fungicidal activity and killed 99.9% of inoculum within 80 and 20 min of exposure respectively at 0.62 mM and 176.8 mM concentrations. Curcumin (5 - 20 mM), camphene (8 - 32 mM) and farnesene (25 - 100 mM), although inhibited planktonic growth, were fungistatic. All the five plant molecules tested in this study inhibited morphogenesis significantly and exhibited considerable activity against biofilm formation. Inhibition of biofilm was found to be stage specific i.e. efficacy was more against adhesion followed by developing and mature biofilm. Plant molecules tested exhibited excellent synergy with fluconazole. However FIC index values 0.155, 0.062 and 0.046 indicate that ocimene was the most effective synergistic molecule inhibited planktonic growth, developing biofilm and mature biofilm growth respectively at very low concentrations. This is the first report of anti-Candida activity of three terpenoids viz. ocimene, farnesene and camphene against planktonic & biofilm growth, morphogenesis as well as synergy with FLC. Plant molecules tested in this study may find use in antifungal chemotherapy individually and or in a combination with FLC.
Highlights
Fungal pathogens are infecting billions of people every year and deaths due to fungal infections are almost equal to that of Tuberculosis, Malaria etc. [1] [2]
C. albicans (ATCC 10231) is a FLC resistant strain (MIC is128 μg/ml) used as a FLC resistant member in a C. albicans Drug resistant Panel MP-8 developed by ATCC for drug testing (CaDR MP-8 Panel, ATCC)
minimum inhibitory concentration (MIC) of remaining four molecules were ranged from 5 - 20 mM, 8 - 32 mM, 25 - 100 and 44.1 - 176.4 (Table 1)
Summary
Fungal pathogens are infecting billions of people every year and deaths due to fungal infections are almost equal to that of Tuberculosis, Malaria etc. [1] [2]. It was reported to be associated with caries in children and dental loss [1]-[3]. It is one of the most frequent agent associated with almost 80% of total fungal bloodstream infections commonly called as candidemia and fourth most common agents associated with nosocomial bloodstream infections with about 40% attributable mortality [2]-[5]. Dramatic increase in incidences of C. albicans infections in recent years is associated with the factors like prolonged dosage of broad-spectrum antibiotics, immunosuppressive therapy, extended stay at ICU and patients with AIDs, burns, surgery as well as malignancy etc., that affects either balance in body microflora and or paralyze host immune system [1]-[3] [5]
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