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Candida albicans Infection of Caenorhabditis elegans Induces Antifungal Immune Defenses  [PDF]
Read Pukkila-Worley,Frederick M. Ausubel equal contributor ,Eleftherios Mylonakis equal contributor
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1002074
Abstract: Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6% of the genome) many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through “pattern recognition,” an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs). This study provides new information on the evolution and regulation of the innate immune response to divergent pathogens and demonstrates that nematodes selectively mount specific antifungal defenses at the expense of antibacterial responses.
Antifungal Effect of Echinophora Platyloba’ s Extract against Candida albicans
Majid Avijgan,Massoud Hafizi,Mehdi Saadat,Mohammad Ali Nilforoushzadeh
Iranian Journal of Pharmaceutical Research , 2006,
Abstract: The present study was undertaken to investigate the effectiveness of the ethanolic extract of Echinophora platyloba DC. on Candida albicans. Using the agar dilution method, the growth condition of standard Candida albicans ATCC 10231, cultured on the media containing plant extracts at different concentrations(1, 2, 4, 8, 16, 32, 64, 128 and 256 mg/ml) was studied. The results were recorded twenty one days after the incubation period, maximum time for the growth of fungi. Results showed that the extract of Echinophora platyloba, equal or above the concentration of 2mg/ml, effectively inhibits the growth of Candida albicans. In other words it shows growth on media containing 1mg/ml of the extract. Results of the present study revealed a great promise in the application of Echinophora platyloba extract against Candida albicans. It is concluded that the plant studied could be a good antifungal source.
ANTIFUNGAL ACTIVITY OF STILBENES AGAINST CANDIDA ALBICANS BY TIME KILL ASSAY  [PDF]
S. Nishanth Kumar*, J. V. Siji, Bala Nambisan and C. Mohandas
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: Candida albicans is one of the most important fungi associated with oral candidiasis and the treatment of this fungi is a serious problem today because of the resistance of these fungi against conventionally used drugs. So, there is an urgent need of alternative antifungal substances especially from the natural sources. The study was conducted to examine the MFC and time kill activity of two stilbenes [3, 4', 5-trihydroxystilbene (1) and 3,5-dihydroxy-4-isopropylstilbene (2)] purified from a bacterium associated with entomopathgenic nematode against C. albicans. The activity was also compared to amphotericin B. The cytotoxicity of stilbenes was also tested against normal human cell lines (L231 lung epithelial and FS normal fibroblast). Results showed that stilbenes was effective against C. albicans with MIC and MFC of 64 and 128 μg/ml for compound 1 and 32 and 64 μg/ml for compound 2. The time kill assay of stilbenes against C. albicans was more effective than amphotericin B. No cytotoxicity was recorded for stilbenes upto 200 μg/ml. The strong antifungal activity and low cytotoxicity of stilbenes make it a promising agent for the treatment of Candida.
Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A  [cached]
Shinde Ravikumar B,Chauhan Nitin M,Raut Jayant S,Karuppayil Sankunny M
Annals of Clinical Microbiology and Antimicrobials , 2012, DOI: 10.1186/1476-0711-11-27
Abstract: Background Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms. Methods Combinations of five antifungal drugs- fluconazole (FLC), voriconazole (VOR), caspofungin (CSP), amphotericin B (AmB) and nystatin (NYT) with cyclosporine A (CSA) were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI) of combination effects. Biofilm growth was analyzed using XTT-metabolic assay. Results MICs of various antifungal drugs for planktonic growth of C. albicans were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively. Conclusions The combinations with CSA resulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated C. albicans infections.
Antifungal activity of Cymbopogon winterianus jowitt ex bor against Candida albicans
Oliveira, Wylly Araújo de;Pereira, Fillipe de Oliveira;Luna, Giliara Carol Diniz Gomes de;Lima, Igara Oliveira;Wanderley, Paulo Alves;Lima, Rita Baltazar de;Lima, Edeltrudes de Oliveira;
Brazilian Journal of Microbiology , 2011, DOI: 10.1590/S1517-83822011000200004
Abstract: candida albicans is an opportunistic yeast and a member of the normal human flora that commonly causes infections in patients with any type of deficiency of the immune system. the essential oils have been tested for antimycotic activity and pose much potential as antifungal agents. this work investigated the activity of the essential oil of cymbopogon winterianus against c. albicans by mic, mfc and time-kill methods. the essential oil (eo) was obtained by hydrodistillation using a clevenger-type apparatus. it was tested fifteen strains of c. albicans. the mic was determined by the microdilution method and the mfc was determined when an aliquot of the broth microdilution was cultivated in sda medium. the phytochemical analysis of eo showed presence of citronellal (23,59%), geraniol (18,81%) and citronellol (11,74%). the eo showed antifungal activity, and the concentrations 625 μg/ml and 1250 μg/ml inhibited the growth of all strains tested and it was fungicidal, respectively. the antimicrobial activity of various concentrations of eo was analyzed over time, it was found concentration-dependent antifungal activity, whose behavior was similar to amphotericin b and nystatin.
Hsp21 Potentiates Antifungal Drug Tolerance in Candida albicans  [PDF]
Fran?ois L. Mayer, Duncan Wilson, Bernhard Hube
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060417
Abstract: Systemic infections of humans with the fungal pathogen Candida albicans are associated with a high mortality rate. Currently, efficient treatment of these infections is hampered by the relatively low number of available antifungal drugs. We recently identified the small heat shock protein Hsp21 in C. albicans and demonstrated its fundamental role for environmental stress adaptation and fungal virulence. Hsp21 was found in several pathogenic Candida species but not in humans. This prompted us to investigate the effects of a broad range of different antifungal drugs on an Hsp21-null C. albicans mutant strain. Our results indicate that combinatorial therapy targeting Hsp21, together with specific antifungal drug targets, has strong synergistic potential. In addition, we demonstrate that Hsp21 is required for tolerance to ethanol-induced stress and induction of filamentation in response to pharmacological inhibition of Hsp90. These findings might pave the way for the development of new treatment strategies against Candida infections.
Antibacterial and Antifungal Activity of Iranian Propolis Against Staphylococcus aureus and Candida albicans
Yousef-Beigi Ghasem,Ownagh Abdolghaffar,M. Hasanloei
Pakistan Journal of Biological Sciences , 2007,
Abstract: Propolis samples from West North region of Iran were studied for their antibacterial (against Staphylococcus aureus) and antifungal (against Candida albicans) activities. In this article, yield of extracts and their pH values were measured. Antibacterial and antifungal activities of Ethanol- Extracted Propolis (EEP) were investigated by Petri dish bioassay method. Dilutions of EPP in agar with serial concentrations ranging from 0/04 to 10% (W/V) were prepared and antimicrobial activities were determined as Minimal Inhibitory Concentrations (MIC). All samples were active against the fungal and bacterial test strains. MIC values for different propolis samples against Staphylococcus aureus were, respectively 4, 3 and 1.5% (W/V) and against Candida albicans were, respectively 2, 4 and 3% (W/V).
Antifungal susceptibility of Candida albicans isolated from oral mucosa of patients with cancer
COSTA, Lino Jo?o da;BIRMAN, Esther Goldenberg;ALVES, Sidney Hartz;CURY, Arlete Emily;
Revista de Odontologia da Universidade de S?o Paulo , 1999, DOI: 10.1590/S0103-06631999000300003
Abstract: the increasing number of oral infections due to opportunistic fungi in immunocompromised patients, needs a new evaluation of the drugs in use. the susceptibility in vitro of candida albicans strains from the oral mucosa of cancer patients to amphotericin b, ketoconazole, miconazole, fluconazole and itraconazole were evaluated. a dilution technique in ynb agar or subculture on sabouraud agar was utilised for mic or mfc determinations. with this methodology, the best fungicidal drug for c.albicans collected from the oral mucosa of 40 cancer patients, divided in two groups: one treated by radiotherapy and the other not, the best results were obtained with amphotericin b, presenting low values of mic compared to azoles and mfc values. however it is important to take into consideration the utilisation in vivo of this polyenic antibiotic and the possible toxic levels necessary to achieve good results. the coexistence of other fungi and the local conditions must also be pondered with these patients, who are mostly undergoing radiotherapy. in order to achieve better results without undesirable consequences, higher levels of mic are expected with the daily clinical use of new drugs.
Antifungal susceptibility of Candida albicans isolated from oral mucosa of patients with cancer  [cached]
COSTA Lino Jo?o da,BIRMAN Esther Goldenberg,ALVES Sidney Hartz,CURY Arlete Emily
Revista de Odontologia da Universidade de S?o Paulo , 1999,
Abstract: The increasing number of oral infections due to opportunistic fungi in immunocompromised patients, needs a new evaluation of the drugs in use. The susceptibility in vitro of Candida albicans strains from the oral mucosa of cancer patients to amphotericin B, ketoconazole, miconazole, fluconazole and itraconazole were evaluated. A dilution technique in YNB agar or subculture on Sabouraud agar was utilised for MIC or MFC determinations. With this methodology, the best fungicidal drug for C.albicans collected from the oral mucosa of 40 cancer patients, divided in two groups: one treated by radiotherapy and the other not, the best results were obtained with amphotericin B, presenting low values of MIC compared to azoles and MFC values. However it is important to take into consideration the utilisation in vivo of this polyenic antibiotic and the possible toxic levels necessary to achieve good results. The coexistence of other fungi and the local conditions must also be pondered with these patients, who are mostly undergoing radiotherapy. In order to achieve better results without undesirable consequences, higher levels of MIC are expected with the daily clinical use of new drugs.
Calcofluor White Combination Antifungal Treatments for Trichophyton rubrum and Candida albicans  [PDF]
Joanne M. Kingsbury, Joseph Heitman, Sheldon R. Pinnell
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039405
Abstract: Superficial mycoses caused by dermatophyte fungi are among the most common infections worldwide, yet treatment is restricted by limited effective drugs available, drug toxicity, and emergence of drug resistance. The stilbene fluorescent brightener calcofluor white (CFW) inhibits fungi by binding chitin in the cell wall, disrupting cell wall integrity, and thus entails a different mechanism of inhibition than currently available antifungal drugs. To identify novel therapeutic options for the treatment of skin infections, we compared the sensitivity of representative strains of the dermatophyte Trichophyton rubrum and Candida albicans to CFW and a panel of fluorescent brighteners and phytoalexin compounds. We identified the structurally related stilbene fluorescent brighteners 71, 85, 113 and 134 as fungicidal to both T. rubrum and C. albicans to a similar degree as CFW, and the stilbene phytoalexins pinosylvan monomethyl ether and pterostilbene inhibited to a lesser degree, allowing us to develop a structure-activity relationship for fungal inhibition. Given the abilities of CFW to absorb UV365 nm and bind specifically to fungal cell walls, we tested whether CFW combined with UV365 nm irradiation would be synergistic to fungi and provide a novel photodynamic treatment option. However, while both treatments individually were cytocidal, UV365 nm irradiation reduced sensitivity to CFW, which we attribute to CFW photoinactivation. We also tested combination treatments of CFW with other fungal inhibitors and identified synergistic interactions between CFW and some ergosterol biosynthesis inhibitors in C. albicans. Therefore, our studies identify novel fungal inhibitors and drug interactions, offering promise for combination topical treatment regimes for superficial mycoses.
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