Candida albicans isolated from human fungaemia induces apoptosis in an experimental endocarditis model

Hernandez-Cañaveral, Iván; Gerardo, Becerra; Jiménez-Cordero, Alberto; Michel, Jean-Baptiste; Plascencia, Arturo; Dominguez-Hernandez, Miguel

doi:10.1590/s0074-02762009000600006

Cited by 3 publications

(3 citation statements)

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“…The lesions in the mucosal surface caused by Saps 4 -6 should create openings for the invasion of C. albicans hypha. These virulence activities can also explain previously observed apoptosis during the early phase of C. albicans infection of oral epithelial cells (40), endomyocardial cells (41), and macrophages (42), which was dependent on the proteolysis by aspartic proteases. The discrepancy of the extent of virulence of C. albicans mutants lacking Saps 4 -6 in different studies may be attributed to the use of different epithelial systems (15)(16)(17)43), since they may have different abundances and types of cell surface integrins.…”

Section: Discussionsupporting

confidence: 69%

Candida albicanssecreted aspartic proteases 4–6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism

Downs

Ghosh³

et al. 2013

FASEB j.

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Systemic infection by the pathogenic yeast Candida albicans produces high mortality in immune-compromised people. Such infection starts with the penetration of the organism at the mucosal surfaces, facilitated by the secreted aspartic proteases (Saps) 4, 5, and 6. The functional mechanism of these virulence factors is unclear. We discovered that Saps 4-6 each contains amino acid motifs RGD/KGD to bind integrins on epithelial cell A549 and are internalized to endosomes and lysosomes. These processes are inhibited by RGD-containing peptides or by substituting RGD motifs of these Saps. The internalization of Saps 4-6 results in partial permeabilization of lysosomal membranes, measured by the redistribution of the lysosomal tropic dye acridine orange to the cytosol, and the triggering of apoptosis via caspase activation. Sap 2 and mutated Saps 4-6 contain no RGD motif, are ineffective in these processes, and a proteolytic inhibitor abolished Sap 4 activity in lysosome permeabilization. Same results were also seen for human tongue keratinocyte SCC-15 cells. Mucosal lesions from this fundamental new mechanism may permit C. albicans to enter the body and may be used to attack cells in immune defense during systemic infections. RGD-motif may also be incorporated in Sap inhibitors for Candidiasis drugs targeting to lysosomes.

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Section: Discussionsupporting

confidence: 69%

Candida albicanssecreted aspartic proteases 4–6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism

Downs

Ghosh³

et al. 2013

FASEB j.

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“…The invasive capacity of C. albicans is due to its cell wall composition, as well as by the enzymes that it expresses, including proteases and inflammatory cytokines (Filler & Sheppard 2006). Moreover, C. albicans is capable of biofilm formation, which serves as a barrier to block the penetration of antimicrobial agents (Hernández-Cañaveral et al 2009) and confers resistance to several antifungals, resulting in a high rate of mortality for patients with endocarditis.…”

Section: Discussionmentioning

confidence: 99%

“…However, while the activity of antifungal agents in cultures is widely used (Habib 2006), there is no guarantee of its in vivo effect in endocarditis caused by bacteria capable of biofilm formation (Hernández-Cañaveral et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans

Victorio

Brennan-Bourdon

García-Benavides

et al. 2017

Mem. Inst. Oswaldo Cruz

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BACKGROUND Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections.OBJECTIVE To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis.METHODS Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis.FINDINGS Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B.CONCLUSIONS The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

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Molecular Pathogenesis of Infective Endocarditis

Brinkman

Patel

2015

Molecular Medical Microbiology

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Candida albicans isolated from human fungaemia induces apoptosis in an experimental endocarditis model

Cited by 3 publications

References 25 publications

Candida albicanssecreted aspartic proteases 4–6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism

Candida albicanssecreted aspartic proteases 4–6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism

Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans

Molecular Pathogenesis of Infective Endocarditis

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