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Responses of Candida albicans to the Human Antimicrobial Peptide LL-37
Pei-Wen Tsai , Yin-Lien Cheng , Wen-Ping Hsieh , Chung-Yu Lan
J. Microbiol. 2014;52(7):581-589.   Published online May 30, 2014
DOI: https://doi.org/10.1007/s12275-014-3630-2
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AbstractAbstract
Candida albicans is a major fungal pathogen in humans. Antimicrobial peptides (AMPs) are critical components of the innate immune response in vertebrates and represent the first line of defense against microbial infection. LL-37 is the only member of the human family of cathelicidin AMPs and is commonly expressed by various tissues and cells, including surfaces of epithelia. The candidacidal effects of LL-37 have been well documented, but the mechanisms by which LL-37 kills C. albicans are not completely understood. In this study, we examined the effects of LL-37 on cell wall and cellular responses in C. albicans. Using transmission electron microscopy, carbohydrate analyses, and staining for β-1,3-glucan, changing of C. albicans cell wall integrity was detected upon LL-37 treatment. In addition, LL-37 also affected cell wall architecture of the pathogen. Finally, DNA microarray analysis and quantitative PCR demonstrated that sub-lethal concentrations of LL-37 modulated the expression of genes with a variety of functions, including transporters, regulators for biological processes, response to stress or chemical stimulus, and pathogenesis. Together, LL-37 induces complex responses in C. albicans, making LL-37 a promising candidate for use as a therapeutic agent against fungal infections.

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Journal Article
Cyclooxygenase Inhibitors Reduce Biofilm Formation and Yeast-Hypha Conversion of Fluconazole Resistant Candida albicans
E. Abdelmegeed , Mona Ibrahim Shaaban
J. Microbiol. 2013;51(5):598-604.   Published online September 14, 2013
DOI: https://doi.org/10.1007/s12275-013-3052-6
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  • 26 Crossref
AbstractAbstract
The incidence of fluconazole-resistant Candida albicans has been increasing worldwide. Both biofilm and fungal morphogenesis are main virulence factors of C. albicans cells. Extracellular fungal prostaglandins are synthesized during biofilm adhesion and development and through yeast-hypha conversion. Hence, we targeted prostaglandin synthesis with various cyclooxygenase (COX) inhibitors (aspirin, diclofenac, ketoprofen, tenoxicam, and ketorolac) and assessed their effect on fungal adhesion, biofilm formation, and yeast-hypha conversion in clinical isolates of Fluconazole resistant C. albicans. Significant reduction in fungal adhesion and detachment of mature biofilm was attained down to 1 mM concentrations of anti-inflammatory agents. Microscopical examination of fungal cells in the presence of the tested drugs showed significant reduction of germ tube formation. Therefore, COX inhibitors have a significant effect on reduction of Candida adhesion and biofilm development in correlation with fungal morphogenesis. Moreover, inhibition of C. albicans by COX inhibitors gave synergistic activity with fluconazole suggesting that combination therapeutic strategies may be fruitful for management of infection of Fluconazole resistant C. albicans.

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Research Support, Non-U.S. Gov'ts
Asc1p, a Ribosomal Protein, Plays a Pivotal Role in Cellular Adhesion and Virulence in Candida albicans
Se Woong Kim , Yoo Jin Joo , Joon Kim
J. Microbiol. 2010;48(6):842-848.   Published online January 9, 2011
DOI: https://doi.org/10.1007/s12275-010-0422-1
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  • 16 Scopus
AbstractAbstract
Candida albicans, the common human fungal pathogen, can switch morphology from yeast to pseudohyphal or hyphal form upon various environmental cues. It is well-known that the ability of morphological conversion and adhesive growth renders C. albicans virulent. It is noteworthy that every factor involved in the morphogenesis is known to be important for the virulence of this pathogen. To examine a functional relevance of Asc1p, a ribosomal protein, in morphogenesis and virulence, an asc1 homozygous null mutant was generated. Although a normal morphological transition of the asc1 deletion strain in liquid media was found, it did not change its morphology on solid media. Moreover, the adhesion activity and hyphal-specific gene expression were defective due to ASC1 deletion. Finally, it was found that the asc1 null mutant was avirulent in a mouse model. These results strongly suggested that Asc1p a component of the 40S ribosomal subunit and a signal transducer, plays a pivotal role in cellular adhesion and virulence through regulation of specific gene expression in C. albicans.
Proteomic Analysis of Hyphae-Specific Proteins That Are Expressed Differentially in cakem1/cakem1 Mutant Strains of Candida albicans
Kang-Hoon Lee , Seung-Yeop Kim , Jong-Hwan Jung , Jinmi Kim
J. Microbiol. 2010;48(3):365-371.   Published online June 23, 2010
DOI: https://doi.org/10.1007/s12275-010-9155-4
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AbstractAbstract
The yeast-to-hyphal transition is a major virulence factor in the fungal pathogen Candida albicans. Mutations in the CaKEM1 gene, which encodes a 5′-3′ exoribonuclease responsible for mRNA degradation, show a defect in hyphal growth. We applied two-dimensional gel electrophoresis to identify hyphae-specific proteins that have altered expressions in the presence of the cakem1 mutation. Eight proteins, Eno1, Eps1, Fba1, Imh3, Lpd1, Met6, Pdc11, and Tsa1 were upregulated during hyphal transition in wild-type but not in cakem1/cakem1 mutant cells. A second group of proteins, Idh1, Idh2, and Ssb1, showed increased levels of expression in cakem1/cakem1 mutant cells when compared to wild-type cells. Overexpression of Lpd1, a component of the pyruvate dehydrogenase complex, caused slight hyperfilamentation in a wild-type strain and suppressed the filamentation defect of the cakem1 mutation. The Ssb1 protein, which is a potential heat shock protein, and the Imh3 protein, which is a putative enzyme in GMP biosynthesis also showed the filamentation-associated phenotypes.
The Photodynamic Effect of Methylene Blue and Toluidine Blue on Candida albicans Is Dependent on Medium Conditions
Gabriela Guimarães Carvalho , Monalisa Poliana Felipe , Maricilia Silva Costa
J. Microbiol. 2009;47(5):619-623.   Published online October 24, 2009
DOI: https://doi.org/10.1007/s12275-009-0059-0
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AbstractAbstract
Due to the increased number of immunocompromised patients, the infections associated with the pathogen of the genus Candida and other fungi have increased dramatically. Photodynamic antimicrobial chemotherapy (PACT) has been presented as a potential antimicrobial therapy, in a process that combines light and a photosensitizing drug, which promotes a phototoxic response by the treated cells. In this work, we studied the effects of the different medium conditions during PACT, using either methylene blue (MB) or toluidine blue (TB) on Candida albicans. The inhibition of the growth produced by PACT was decreased for different pH values (6.0, 7.0, and 8.0) in a buffered medium. The phototoxic effects were observed only in the presence of saline (not buffered medium). PACT was modulated by calcium in a different manner using either MB or TB. Also when using MB both verapamil or sodium azide were able to decrease the phototoxic effects on the C. albicans. These results show that PACT is presented as a new and promising antifungal therapy, however, new studies are necessary to understand the mechanism by which this event occurs.

Journal of Microbiology : Journal of Microbiology
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