Activity of Antimicrobial Peptide Mimetics in the Oral Cavity: I. Activity Against Biofilms of Candida albicans
Identifieur interne : 003246 ( Ncbi/Merge ); précédent : 003245; suivant : 003247Activity of Antimicrobial Peptide Mimetics in the Oral Cavity: I. Activity Against Biofilms of Candida albicans
Auteurs : Jianyuan Hua [États-Unis] ; Radha Yamarthy [États-Unis] ; Shaina Felsenstein [États-Unis] ; Richard W. Scott [États-Unis] ; Kenneth Markowitz [États-Unis] ; Gill Diamond [États-Unis]Source :
- Molecular oral microbiology [ 2041-1006 ] ; 2010.
Abstract
Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as
Url:
DOI: 10.1111/j.2041-1014.2010.00590.x
PubMed: 21040515
PubMed Central: 2992321
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<series><title level="j">Molecular oral microbiology</title>
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<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p id="P1">Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as <italic>Candida albicans</italic>
, however numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (MW <1,000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against <italic>C. albicans</italic>
. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-MIC levels did not lead to resistant Candida in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.</p>
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<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101524770</journal-id>
<journal-id journal-id-type="pubmed-jr-id">37302</journal-id>
<journal-id journal-id-type="nlm-ta">Mol Oral Microbiol</journal-id>
<journal-title>Molecular oral microbiology</journal-title>
<issn pub-type="ppub">2041-1006</issn>
<issn pub-type="epub">2041-1014</issn>
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<article-id pub-id-type="manuscript">NIHMS231206</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
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<title-group><article-title>Activity of Antimicrobial Peptide Mimetics in the Oral Cavity: I. Activity Against Biofilms of Candida albicans</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hua</surname>
<given-names>Jianyuan</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
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<contrib contrib-type="author"><name><surname>Yamarthy</surname>
<given-names>Radha</given-names>
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<contrib contrib-type="author"><name><surname>Felsenstein</surname>
<given-names>Shaina</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
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<contrib contrib-type="author"><name><surname>Scott</surname>
<given-names>Richard W.</given-names>
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<xref rid="A2" ref-type="aff">2</xref>
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<contrib contrib-type="author"><name><surname>Markowitz</surname>
<given-names>Kenneth</given-names>
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<xref rid="A1" ref-type="aff">1</xref>
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<contrib contrib-type="author"><name><surname>Diamond</surname>
<given-names>Gill</given-names>
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<xref rid="A1" ref-type="aff">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
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<aff id="A1"><label>1</label>
Department of Oral Biology, UMDNJ-New Jersey Dental School, Newark, NJ 07101</aff>
<aff id="A2"><label>2</label>
PolyMedix, Inc., Radnor, PA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Correspondence: Dr. Gill Diamond, Department of Oral Biology, UMDNJ-New Jersey Dental School, 185 South Orange Ave., Newark, NJ 07103, USA, Tel: 973-972-3324, Fax: 973-972-0045, <email>gdiamond@umdnj.edu</email>
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<year>2010</year>
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<year>2011</year>
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<volume>25</volume>
<issue>6</issue>
<fpage>418</fpage>
<lpage>425</lpage>
<abstract><title>Summary</title>
<p id="P1">Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as <italic>Candida albicans</italic>
, however numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (MW <1,000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against <italic>C. albicans</italic>
. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-MIC levels did not lead to resistant Candida in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.</p>
</abstract>
<kwd-group><kwd>antifungal</kwd>
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<kwd>resistance</kwd>
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<contract-num rid="DE1">R43 DE018371-01A2
||DE</contract-num>
<contract-sponsor id="DE1">National Institute of Dental and Craniofacial Research : NIDCR</contract-sponsor>
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</front>
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<affiliations><list><country><li>États-Unis</li>
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