Studies of the mechanism of human salivary histatin-5 candidacidal activity with histatin-5 variants and azole-sensitive and -resistant Candida species

Tsai, H.; Bobek, Libuse A.

doi:10.1128/aac.41.10.2224

Cited by 67 publications

(40 citation statements)

References 31 publications

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“…It has recently become an emerging agent of nosocomial infections and yet little is known about its epidemiology [50]. This yeast is particularly important because it has high intrinsic resistance to certain antifungal agents, especially azoles [51]. Studies have shown resistance cases for azoles (fluconazole, voriconazole, itraconazole and pozaconazol) as well as for echinocandins anidulafungin, caspofungin and micofungina [4,[52][53][54].…”

Section: Discussionmentioning

confidence: 99%

Antifungal Activity of Extracts and Isolated Compounds from Buchenavia Tomentosa on Candida Albicans and non- albicans

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Antifungal Activity of Extracts and Isolated Compounds from Buchenavia Tomentosa on Candida Albicans and non- albicans

et al. 2015

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“…Indeed, saliva is swallowed at the rate of ~1 mL per minute. The constituent antimicrobial proteins and peptides of whole saliva include cystatins [34] and histatins [35,36], lysozyme, lactoferrin and lactoperoxidase [37], defensins [38], cathelicidin [39], and calprotectin (S100A8/A9) [40]. The antimicrobial proteins/peptides all likely limit the overgrowth of many species in the dental biofilm.…”

Section: Characteristics Of Different Oral Ecological Nichesmentioning

confidence: 99%

The oral microbiome and the immunobiology of periodontal disease and caries

2014

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The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth. Caries is a unique infection of the dental hard tissues. The initiation of both diseases is marked by an increase in the complexity of the microbiome. In periodontitis, pathobionts and keystone pathogens such as Porphyromonas gingivalis appear in greater proportion than in health. As a keystone pathogen, P. gingivalis impairs host immune responses and appears necessary but not sufficient to cause periodontitis. Historically, dental caries had been causally linked to Streptococcus mutans. Contemporary microbiome studies now indicate that singular pathogens are not obvious in either caries or periodontitis. Both diseases appear to result from a perturbation among relatively minor constituents in local microbial communities resulting in dysbiosis. Emergent consortia of the minor members of the respective microbiomes act synergistically to stress the ability of the host to respond and protect. In periodontal disease, host protection first occurs at the level of innate gingival epithelial immunity. Secretory IgA antibody and other salivary antimicrobial systems also act against periodontopathic and cariogenic consortia. When the gingival immune response is impaired, periodontal tissue pathology results when matrix metalloproteinases are released from neutrophils and T cells mediate alveolar bone loss. In caries, several species are acidogenic and aciduric and appear to work synergistically to promote demineralization of the enamel and dentin. Whereas technically possible, particularly for caries, vaccines are unlikely to be commercialized in the near future because of the low morbidity of caries and periodontitis.

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“…and an amphotericin B-resistant laboratory strain of C. albicans (Helmerhorst et al 1999;Tsai and Bobek 1997). The distinct mode of action displayed by histatin 5, compared with that of azoles or polyenes, may advance its use when resistance to conventional antifungals has emerged.…”

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Susceptibility of Candida biofilms to histatin 5 and fluconazole

Konopka

Dorocka‐Bobkowska

Gebremedhin

et al. 2010

Antonie van Leeuwenhoek

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Candida-associated denture stomatitis has a high rate of recurrence. Candida biofilms formed on denture acrylic are more resistant to antifungals than planktonic yeasts. Histatins, a family of basic peptides secreted by the major salivary glands in humans, especially histatin 5, possess significant antifungal properties. We examined antifungal activities of histatin 5 against planktonic or biofilm Candida albicans and Candida glabrata. Candida biofilms were developed on poly(methyl methacrylate) discs and treated with histatin 5 (0.01-100 microM) or fluconazole (1-200 microM). The metabolic activity of the biofilms was measured by the XTT reduction assay. The fungicidal activity of histatin 5 against planktonic Candida was tested by microdilution plate assay. Biofilm and planktonic C. albicans GDH18, UTR-14 and 6122/06 were highly susceptible to histatin 5, with 50% RMA (concentration of the agent causing 50% reduction in the metabolic activity; biofilm) of 4.6 +/- 2.2, 6.9 +/- 3.7 and 1.7 +/- 1.5 microM, and IC(50) (planktonic cells) of 3.0 +/- 0.5, 2.6 +/- 0.1 and 4.8 +/- 0.5, respectively. Biofilms of C. glabrata GDH1407 and 6115/06 were less susceptible to histatin 5, with 50% RMA of 31.2 +/- 4.8 and 62.5 +/- 0.7 microM, respectively. Planktonic C. glabrata was insensitive to histatin 5 (IC(50) > 100 microM). Biofilm-associated Candida was highly resistant to fluconazole in the range 1-200 microM; e.g. at 100 microM only approximately 20% inhibition was observed for C. albicans, and approximately 30% inhibition for C. glabrata. These results indicate that histatin 5 exhibits antifungal activity against biofilms of C. albicans and C. glabrata developed on denture acrylic. C. glabrata is significantly less sensitive to histatin 5 than C. albicans.

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Studies of the mechanism of human salivary histatin-5 candidacidal activity with histatin-5 variants and azole-sensitive and -resistant Candida species

Cited by 67 publications

References 31 publications

Antifungal Activity of Extracts and Isolated Compounds from Buchenavia Tomentosa on Candida Albicans and non- albicans

Antifungal Activity of Extracts and Isolated Compounds from Buchenavia Tomentosa on Candida Albicans and non- albicans

The oral microbiome and the immunobiology of periodontal disease and caries

Susceptibility of Candida biofilms to histatin 5 and fluconazole

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