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Article: Fungicidal effect of three new synthetic cationic peptides against Candida albicans

TitleFungicidal effect of three new synthetic cationic peptides against Candida albicans
Authors
Issue Date2004
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1354-523X&site=1
Citation
Oral Diseases, 2004, v. 10 n. 4, p. 221-228 How to Cite?
AbstractOBJECTIVE: Peptide antibiotics are considered a new class of antifungal agents. Of these, an α-helical, cationic peptide termed Dhvar 4, a relative of salivary histatin has been shown to be an antifungal of relatively high potency. Similarly, lactoferricin B (LFB) and a derivative thereof, LFB(17-30), disrupts the fungal cell membrane and acts against Candida albicans. As Dhvar 4 and LFB(17-30), exhibit almost identical amino acid sequences at their C-terminal, we hypothesized that laboratory synthesis of peptides with an α-helical structure and having similar amphipathic properties could lead to products with candidacidal activity. Hence, three such peptides - JH8194, JH8195 and JH 8944, were synthesized and their antifungal properties compared with recognized antifungals LFB, LFB(17-30), human lactoferricin (LFH), Histatin-5 and Dhvar 4, against two isolates of C. albicans. MATERIALS AND METHODS: The antifungal agents were synthesized and their secondary structures evaluated according to a previously described protocol of Situ and Bobek (2000) Antimicrob Agents Chemother 44: 1485-1493. The C. albicans strains were oral isolates from a human immunodeficiency virus-infected (isolate A2) and a healthy (A6) individual. A standard concentration of yeasts was exposed to a range of dilutions of the agents for a specific duration and the cell death (viability) in terms of the resultant colony forming units ml-1 was quantified. RESULTS: Dhvar 4, showed the most α-helical propensity, and was the least fungicidal while LFB and LFB(17-30) showed the highest antifungal potential, and demonstrated total kill of A6, and A2 at 5 and 10 μM concentrations, respectively whilst LFH killed both isolates at a 10 μM concentration. Of the three new synthetic peptides, JH 8194 was the most potent (total kill of A6/A2 strains at 1.25/2.5 μM), followed by JH 8195 (total kill of A6/A2 strains at 5/10 μM while JH 8944 was the least potent as a 25 μM concentration was required to kill either strain of Candida. On further analyses of the relationship between pl value of the peptides and their anticandicidal activity, a significant positive correlation was noted. In order to rule out a cytotoxic effect of the new synthetic peptides we compared the fungicidal and hemolytic activities under similar incubation conditions using freshly isolated erythrocytes and all three peptides exhibited no detectable hemolysis upto an concentration of 100 μM in contrast to the polyene antifungal amphotericin B that elicited significant initiation of hemolysis at a concentration of 5.0 μM. CONCLUSION: Our data suggest that laboratory synthesis of agents with an α-helical structure and having amphipathic properties similar to known, natural antifungal agents may be a promising avenue to generate products with improved antifungal activity.
Persistent Identifierhttp://hdl.handle.net/10722/66956
ISSN
2015 Impact Factor: 2.0
2015 SCImago Journal Rankings: 0.828
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNikawa, Hen_HK
dc.contributor.authorFakashima, Hen_HK
dc.contributor.authorMakihira, Sen_HK
dc.contributor.authorHamada, Ten_HK
dc.contributor.authorSamaranayake, LPen_HK
dc.date.accessioned2010-09-06T05:50:45Z-
dc.date.available2010-09-06T05:50:45Z-
dc.date.issued2004en_HK
dc.identifier.citationOral Diseases, 2004, v. 10 n. 4, p. 221-228en_HK
dc.identifier.issn1354-523Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/66956-
dc.description.abstractOBJECTIVE: Peptide antibiotics are considered a new class of antifungal agents. Of these, an α-helical, cationic peptide termed Dhvar 4, a relative of salivary histatin has been shown to be an antifungal of relatively high potency. Similarly, lactoferricin B (LFB) and a derivative thereof, LFB(17-30), disrupts the fungal cell membrane and acts against Candida albicans. As Dhvar 4 and LFB(17-30), exhibit almost identical amino acid sequences at their C-terminal, we hypothesized that laboratory synthesis of peptides with an α-helical structure and having similar amphipathic properties could lead to products with candidacidal activity. Hence, three such peptides - JH8194, JH8195 and JH 8944, were synthesized and their antifungal properties compared with recognized antifungals LFB, LFB(17-30), human lactoferricin (LFH), Histatin-5 and Dhvar 4, against two isolates of C. albicans. MATERIALS AND METHODS: The antifungal agents were synthesized and their secondary structures evaluated according to a previously described protocol of Situ and Bobek (2000) Antimicrob Agents Chemother 44: 1485-1493. The C. albicans strains were oral isolates from a human immunodeficiency virus-infected (isolate A2) and a healthy (A6) individual. A standard concentration of yeasts was exposed to a range of dilutions of the agents for a specific duration and the cell death (viability) in terms of the resultant colony forming units ml-1 was quantified. RESULTS: Dhvar 4, showed the most α-helical propensity, and was the least fungicidal while LFB and LFB(17-30) showed the highest antifungal potential, and demonstrated total kill of A6, and A2 at 5 and 10 μM concentrations, respectively whilst LFH killed both isolates at a 10 μM concentration. Of the three new synthetic peptides, JH 8194 was the most potent (total kill of A6/A2 strains at 1.25/2.5 μM), followed by JH 8195 (total kill of A6/A2 strains at 5/10 μM while JH 8944 was the least potent as a 25 μM concentration was required to kill either strain of Candida. On further analyses of the relationship between pl value of the peptides and their anticandicidal activity, a significant positive correlation was noted. In order to rule out a cytotoxic effect of the new synthetic peptides we compared the fungicidal and hemolytic activities under similar incubation conditions using freshly isolated erythrocytes and all three peptides exhibited no detectable hemolysis upto an concentration of 100 μM in contrast to the polyene antifungal amphotericin B that elicited significant initiation of hemolysis at a concentration of 5.0 μM. CONCLUSION: Our data suggest that laboratory synthesis of agents with an α-helical structure and having amphipathic properties similar to known, natural antifungal agents may be a promising avenue to generate products with improved antifungal activity.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1354-523X&site=1en_HK
dc.relation.ispartofOral Diseasesen_HK
dc.subject.meshAmino Acid Sequenceen_HK
dc.subject.meshAntifungal Agents - chemical synthesis - pharmacologyen_HK
dc.subject.meshAntimicrobial Cationic Peptides - chemical synthesis - pharmacologyen_HK
dc.subject.meshCandida albicans - drug effectsen_HK
dc.subject.meshCircular Dichroismen_HK
dc.subject.meshColony Count, Microbialen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHemolysisen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIsoelectric Pointen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMicrobial Sensitivity Testsen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshProtein Structure, Secondaryen_HK
dc.titleFungicidal effect of three new synthetic cationic peptides against Candida albicansen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1354-523X&volume=10&spage=221&epage=228&date=2004&atitle=Fungicidal+effect+of+three+new+synthetic+cationic+peptides+against+Candida+albicansen_HK
dc.identifier.emailSamaranayake, LP:lakshman@hku.hken_HK
dc.identifier.authoritySamaranayake, LP=rp00023en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1601-0825.2004.01010.xen_HK
dc.identifier.pmid15196144-
dc.identifier.scopuseid_2-s2.0-3042755651en_HK
dc.identifier.hkuros89112en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3042755651&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue4en_HK
dc.identifier.spage221en_HK
dc.identifier.epage228en_HK
dc.identifier.isiWOS:000221977900006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNikawa, H=7006724162en_HK
dc.identifier.scopusauthoridFakashima, H=6504057318en_HK
dc.identifier.scopusauthoridMakihira, S=6603833899en_HK
dc.identifier.scopusauthoridHamada, T=7401759268en_HK
dc.identifier.scopusauthoridSamaranayake, LP=7102761002en_HK

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