Objective:To explore the prevention of rerurrent candiduria using natural based approaches and to study the antimicrobial effect of Hibiscus sabdariffa(H.sabdariffa) extract and the biofilm forming capacity of Candida...Objective:To explore the prevention of rerurrent candiduria using natural based approaches and to study the antimicrobial effect of Hibiscus sabdariffa(H.sabdariffa) extract and the biofilm forming capacity of Candida albicans strains in the present of the H.sabdariffa extract.Methods:In this particular study,six strains of fluconazole resistant Candida albicans isolated from recurrent candiduria were used.The susceptibility of fungal isolates,time-kill curves and biofilm forming capacity in the present of the H.sabdariffa extract were determined.Results:Various levels minimum inhibitory concentration of the extract were observed against all the isolates.Minimum inhibitory concentration values ranged from 0.5 to 2.0 mg/mL Timekill experiment demonstrated that the effect was fungistatic.The biofilm inhibition assay results showed that H.sabdariffa extract inhibited biofilm production of all the isolates.Conclusions:The results of the study support the potential effect of H.sabdariffa extract for preventing recurrent candiduria and emphasize the significance of the plant extract approach as a potential antifungal agent.展开更多
Candida albicans proliferates in the skin and oral cavity and is the causative agent of candida dermatitis and oral candidiasis. C. albicans is known to form biofilms on oral mucosa and denture surfaces. Formation of ...Candida albicans proliferates in the skin and oral cavity and is the causative agent of candida dermatitis and oral candidiasis. C. albicans is known to form biofilms on oral mucosa and denture surfaces. Formation of biofilms deteriorates the permeability of antifungal drugs, decreasing their effectiveness. Therefore, in this study, I identified a compound with inhibitory activity against C. albicans biofilm formation. Heat shock protein 90 was selected as the target protein, and a potential ligand for the same was extracted and identified as 2-(4-methylpiperazin-1-yl)cyclopentanol. C. albicans was then cultured with varying concentrations of this compound: 0 mmol/L, 0.63 mmol/l. 2.5 mmol/l, and 10 mmol/l, and biofilm formation was measured via crystal violet assay. The findings demonstrated that 2-(4-methylpiperazin-1-yl)cyclopentanol substantially inhibits biofilm formation when added at a concentration of 0.63 mmol/l or higher. It is suggested that C. albicans could be eliminated more efficiently using this compound in combination with the existing antifungal drug miconazole. Further, the compound may also be useful as a disinfectant for medical devices, such as catheters, to prevent the formation of C. albicans biofilms.展开更多
Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are the two main pathogens in the clinical setting to cause serious, sometimes, lethal fungal infections. Immunocompromised patients fall victims...Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are the two main pathogens in the clinical setting to cause serious, sometimes, lethal fungal infections. Immunocompromised patients fall victims to these fungi, with a mortality rate rising drastically over the past decades. This is in correlation with the fact that conventional antifungals are no longer capable of completely eradicating the disease, or if so, high doses are usually required to do so, leading to eventual resistance to those drugs and severe side effects. High drug resistance is in association with the discovery that these opportunistic pathogens have the ability to develop a multicellular complex, known as biofilm. Biofilms prevent drugs from reaching the fungal cells by sequestering them in their extracellular matrix. Other factors such as extracellular DNA, persister cells or heat shock protein 90 (Hsp90) also play a role in biofilm and contribute to drug recalcitrance. With the discovery of new antifungals lagging behind, scientists focused on other more profitable ways to counteract this phenomenon. Combination of two or more antifungals was found effective but came with serious drawbacks. Natural plant extracts, such as traditional Chinese medicine have also been demonstrated in vitro to possess antimicrobial actions. Great interest was directed towards their use with conventional antifungal agents with a possibility of lowering the necessary concentration required to inhibit the growth of fungi. This review aims in understanding the different factors contributing to clinical drug resistance and evaluating the effect of combination therapy and natural products on those cases difficult to treat.展开更多
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, de...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.展开更多
Candida albicans has ability to switch from yeast to hyphal form which is an important virulence factor. The objective of the research is to study the effect of Phenazine Methosulphate (PMS) on virulence factors and t...Candida albicans has ability to switch from yeast to hyphal form which is an important virulence factor. The objective of the research is to study the effect of Phenazine Methosulphate (PMS) on virulence factors and to study expression profile in yeast to hyphal form transition in C. albicans. Phenazine Methosulphate (PMS) acted as an inhibitor of yeast to hyphal form transition, adhesion and biofilm formation in C. albicans. RTPCR study demonstrated that PMS Modulate the expression of genes involved in Ras1-cAMP-Efg1 and Cek1-MAPK signal transduction pathways. Cell cycle of C. albicans was arrested at S phase on treatment of PMS. Hyphal suppressor genes like Tup1, Mig1 and Nrg1 were upregulated by PMS. Based on our data on expression of genes during yeast to hyphal form transition in presence and absence of PMS, we hypothesize that inhibition of hyphal formation may be due to the overexpression of negative regulators of hyphal growth. Targeting of hyphal specific genes involved in these pathways may be a promising strategy for anti-candida drug development.展开更多
基金Supported by the Deanship of Scientific Research of Taibah University (Grant No.432/3088)
文摘Objective:To explore the prevention of rerurrent candiduria using natural based approaches and to study the antimicrobial effect of Hibiscus sabdariffa(H.sabdariffa) extract and the biofilm forming capacity of Candida albicans strains in the present of the H.sabdariffa extract.Methods:In this particular study,six strains of fluconazole resistant Candida albicans isolated from recurrent candiduria were used.The susceptibility of fungal isolates,time-kill curves and biofilm forming capacity in the present of the H.sabdariffa extract were determined.Results:Various levels minimum inhibitory concentration of the extract were observed against all the isolates.Minimum inhibitory concentration values ranged from 0.5 to 2.0 mg/mL Timekill experiment demonstrated that the effect was fungistatic.The biofilm inhibition assay results showed that H.sabdariffa extract inhibited biofilm production of all the isolates.Conclusions:The results of the study support the potential effect of H.sabdariffa extract for preventing recurrent candiduria and emphasize the significance of the plant extract approach as a potential antifungal agent.
文摘Candida albicans proliferates in the skin and oral cavity and is the causative agent of candida dermatitis and oral candidiasis. C. albicans is known to form biofilms on oral mucosa and denture surfaces. Formation of biofilms deteriorates the permeability of antifungal drugs, decreasing their effectiveness. Therefore, in this study, I identified a compound with inhibitory activity against C. albicans biofilm formation. Heat shock protein 90 was selected as the target protein, and a potential ligand for the same was extracted and identified as 2-(4-methylpiperazin-1-yl)cyclopentanol. C. albicans was then cultured with varying concentrations of this compound: 0 mmol/L, 0.63 mmol/l. 2.5 mmol/l, and 10 mmol/l, and biofilm formation was measured via crystal violet assay. The findings demonstrated that 2-(4-methylpiperazin-1-yl)cyclopentanol substantially inhibits biofilm formation when added at a concentration of 0.63 mmol/l or higher. It is suggested that C. albicans could be eliminated more efficiently using this compound in combination with the existing antifungal drug miconazole. Further, the compound may also be useful as a disinfectant for medical devices, such as catheters, to prevent the formation of C. albicans biofilms.
文摘Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are the two main pathogens in the clinical setting to cause serious, sometimes, lethal fungal infections. Immunocompromised patients fall victims to these fungi, with a mortality rate rising drastically over the past decades. This is in correlation with the fact that conventional antifungals are no longer capable of completely eradicating the disease, or if so, high doses are usually required to do so, leading to eventual resistance to those drugs and severe side effects. High drug resistance is in association with the discovery that these opportunistic pathogens have the ability to develop a multicellular complex, known as biofilm. Biofilms prevent drugs from reaching the fungal cells by sequestering them in their extracellular matrix. Other factors such as extracellular DNA, persister cells or heat shock protein 90 (Hsp90) also play a role in biofilm and contribute to drug recalcitrance. With the discovery of new antifungals lagging behind, scientists focused on other more profitable ways to counteract this phenomenon. Combination of two or more antifungals was found effective but came with serious drawbacks. Natural plant extracts, such as traditional Chinese medicine have also been demonstrated in vitro to possess antimicrobial actions. Great interest was directed towards their use with conventional antifungal agents with a possibility of lowering the necessary concentration required to inhibit the growth of fungi. This review aims in understanding the different factors contributing to clinical drug resistance and evaluating the effect of combination therapy and natural products on those cases difficult to treat.
文摘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.
文摘Candida albicans has ability to switch from yeast to hyphal form which is an important virulence factor. The objective of the research is to study the effect of Phenazine Methosulphate (PMS) on virulence factors and to study expression profile in yeast to hyphal form transition in C. albicans. Phenazine Methosulphate (PMS) acted as an inhibitor of yeast to hyphal form transition, adhesion and biofilm formation in C. albicans. RTPCR study demonstrated that PMS Modulate the expression of genes involved in Ras1-cAMP-Efg1 and Cek1-MAPK signal transduction pathways. Cell cycle of C. albicans was arrested at S phase on treatment of PMS. Hyphal suppressor genes like Tup1, Mig1 and Nrg1 were upregulated by PMS. Based on our data on expression of genes during yeast to hyphal form transition in presence and absence of PMS, we hypothesize that inhibition of hyphal formation may be due to the overexpression of negative regulators of hyphal growth. Targeting of hyphal specific genes involved in these pathways may be a promising strategy for anti-candida drug development.
