Bcr1 Functions Downstream of Ssd1 To Mediate Antimicrobial Peptide Resistance in Candida albicans

Jung, Seunggon; Finkel, Jonathan S.; Solis, Norma V.; Chaili, Siyang; Mitchell, Aaron P.; Yeaman, Michael R.; Filler, Scott G.

doi:10.1128/ec.00285-12

Cited by 20 publications

(25 citation statements)

References 31 publications

(31 reference statements)

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“…Our observation is consistent with a gene expression study in C. albicans (49), where the bcr1⌬/⌬ mutant showed upregulated mRNA levels of secreted aspartyl proteinase genes (SAP). The function of BCR1 in C. parapsilosis with respect to susceptibility against antimicrobial peptides (protamine, RP-1, and LL-37) is in agreement with a recent study (35) where bcr1⌬/⌬ mutants of C. albicans were shown to display an increased susceptibility to the antimicrobial peptides rational peptide 1 (RP-1), human ␤-defensin 2 (hBD-2), and protamine but not LL-37. The mechanism of action of these antimicrobial peptides in fungi is still unknown.…”

Section: Figsupporting

confidence: 91%

“…Similar to C. albicans, bcr1⌬/⌬ mutants of all strains showed increased susceptibility to protamine and RP-1 compared to wildtype and complemented strains. The resistance to LL-37 was not influenced by BCR1, as reported for C. albicans previously (35).…”

Section: Figsupporting

confidence: 82%

“…The effectiveness of caspofungin against Candida biofilms elevates this drug as a proper candidate for fungal biofilm treatment (43). Recently, it was shown that BCR1 not only affects biofilm formation but also increases susceptibility to antimicrobial peptides in C. albicans (35). We identify here three novel physiological traits of C. parapsilosis regulated by BCR1, namely, colony morphology, asparatyl proteinase secretion, and antimicrobial susceptibility toward antimicrobial peptides.…”

Section: Figmentioning

confidence: 89%

“…The positive control is antimycotic-free biofilm, and its activity was arbitrarily set to 1. bcr1⌬/⌬ mutants show increased susceptibility to protamine and RP-1. Recently, it was reported that the susceptibility of C. albicans to antimicrobial peptides is affected by BCR1 (35). We investigated the effect of BCR1 on susceptibility to the antimicrobial peptides LL-37, protamine, and RP-1 in C. parapsilosis (Fig.…”

Section: Figmentioning

confidence: 99%

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Characterization of Biofilm Formation and the Role of BCR1 in Clinical Isolates of Candida parapsilosis

et al. 2014

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eIn Candida parapsilosis, biofilm formation is considered to be a major virulence factor. Previously, we determined the ability of 33 clinical isolates causing bloodstream infection to form biofilms and identified three distinct groups of biofilm-forming strains (negative, low, and high). Here, we establish two different biofilm structures among strains forming large amounts of biofilm in which strains with complex spider-like structures formed robust biofilms on different surface materials with increased resistance to fluconazole. Surprisingly, the transcription factor Bcr1, required for biofilm formation in Candida albicans and C. parapsilosis, has an essential role only in strains with low capacity for biofilm formation. Although BCR1 leads to the formation of more and longer pseudohyphae, it was not required for initial adhesion and formation of mature biofilms in strains with a high level of biofilm formation. Furthermore, an additional phenotype affected by BCR1 was the switch in colony morphology from rough to crepe, but only in strains forming high levels of biofilm. All bcr1⌬/⌬ mutants showed increased proteolytic activity and increased susceptibility to the antimicrobial peptides protamine and RP-1 compared to corresponding wild-type and complemented strains. Taken together, our results demonstrate that biofilm formation in clinical isolates of C. parapsilosis is both dependent and independent of BCR1, but even in strains which showed a BCR1-independent biofilm phenotype, BCR1 has alternative physiological functions.

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Section: Figsupporting

confidence: 91%

Section: Figsupporting

confidence: 82%

Section: Figmentioning

confidence: 89%

Section: Figmentioning

confidence: 99%

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Characterization of Biofilm Formation and the Role of BCR1 in Clinical Isolates of Candida parapsilosis

et al. 2014

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“…Examples include the secretion of AMP-binding proteins that re- direct peptide antimicrobials away from microbial structures (52). As presented below, similar mechanisms were also shown for C. albicans (53)(54)(55)(56)(57)(58).…”

Section: Escape Strategies From Antimicrobial Peptidesmentioning

confidence: 64%

Interplay between Candida albicans and the Antimicrobial Peptide Armory

2014

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Antimicrobial peptides (AMPs) are key elements of innate immunity, which can directly kill multiple bacterial, viral, and fungal pathogens. The medically important fungus Candida albicans colonizes different host niches as part of the normal human microbiota. Proliferation of C. albicans is regulated through a complex balance of host immune defense mechanisms and fungal responses. Expression of AMPs against pathogenic fungi is differentially regulated and initiated by interactions of a variety of fungal pathogen-associated molecular patterns (PAMPs) with pattern recognition receptors (PRRs) on human cells. Inflammatory signaling and other environmental stimuli are also essential to control fungal proliferation and to prevent parasitism. To persist in the host, C. albicans has developed a three-phase AMP evasion strategy, including secretion of peptide effectors, AMP efflux pumps, and regulation of signaling pathways. These mechanisms prevent C. albicans from the antifungal activity of the major AMP classes, including cathelicidins, histatins, and defensins leading to a basal resistance. This minireview summarizes human AMP attack and C. albicans resistance mechanisms and current developments in the use of AMPs as antifungal agents.

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Membrane damage as first and DNA as the secondary target for anti‐candidal activity of antimicrobial peptide P7 derived from cell‐penetrating peptide ppTG20 against Candida albicans

Song

Sun

et al. 2016

Journal of Peptide Science

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P7, a peptide analogue derived from cell-penetrating peptide ppTG20, possesses antibacterial and antitumor activities without significant hemolytic activity. In this study, we investigated the antifungal effect of P7 and its anti-Candida acting mode in Candida albicans. P7 displayed antifungal activity against the reference C. albicans (MIC = 4 μM), Aspergilla niger (MIC = 32 μM), Aspergillus flavus (MIC = 8 μM), and Trichopyton rubrum (MIC = 16 μM). The effect of P7 on the C. albicans cell membrane was examined by investigating the calcein leakage from fungal membrane models made of egg yolk l-phosphatidylcholine/ergosterol (10 : 1, w/w) liposomes. P7 showed potent leakage effects against fungal liposomes similar to Melittin-treated cells. C. albicans protoplast regeneration assay demonstrated that P7 interacted with the C. albicans plasma membrane. Flow cytometry of the plasma membrane potential and integrity of C. albicans showed that P7 caused 60.9 ± 1.8% depolarization of the membrane potential of intact C. albicans cells and caused 58.1 ± 3.2% C. albicans cell membrane damage. Confocal laser scanning microscopy demonstrated that part of FITC-P7 accumulated in the cytoplasm. DNA retardation analysis was also performed, which showed that P7 interacted with C. albicans genomic DNA after penetrating the cell membrane, completely inhibiting the migration of genomic DNA above the weight ratio (peptide : DNA) of 6. Our results indicated that the plasma membrane was the primary target, and DNA was the secondary intracellular target of the mode of action of P7 against C. albicans. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

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Bcr1 Functions Downstream of Ssd1 To Mediate Antimicrobial Peptide Resistance in Candida albicans

Cited by 20 publications

References 31 publications

Characterization of Biofilm Formation and the Role of BCR1 in Clinical Isolates of Candida parapsilosis

Characterization of Biofilm Formation and the Role of BCR1 in Clinical Isolates of Candida parapsilosis

Interplay between Candida albicans and the Antimicrobial Peptide Armory

Membrane damage as first and DNA as the secondary target for anti‐candidal activity of antimicrobial peptide P7 derived from cell‐penetrating peptide ppTG20 against Candida albicans

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