Evidence map›Paper›PMID 25365968›Full record

ArticleJournal of dental research2015

Iron binding modulates candidacidal properties of salivary histatin 5.

S Puri, R Li, D Ruszaj, S Tati, M Edgerton

Open access · greenAbstract readComparative Study
In one paragraph

Article in Journal of dental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.6field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
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  8. Antimicrobial Peptides with Anti-International journal of molecular sciences · 2022
    Review
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  11. Review
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  13. Review
  14. Review
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  16. Article
  17. Iron Chelator Deferasirox ReducesAntimicrobial agents and chemotherapy · 2019
    Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

S PuriDepartment of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA.
R LiDepartment of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA.
D RuszajDepartment of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
S TatiDepartment of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA.
M EdgertonDepartment of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA edgerto@buffalo.edu.
University at Buffalo, State University of New York · US

Funding

Supplements to Support Candida DNA Microarray FacilitiesR01DE010641 · NIDCR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI EDGERTON, MIRA · 2000 to 2019
$6.7M
Advanced Training in Oral BiologyT32DE023526 · NIDCR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI Stefan Hans-Klaus Ruhl · 2013 to 2026
$3.7M
Regulation of Candida albicans Pathogenesis by the Signaling Mucin Msb2R01DE022720 · NIDCR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CULLEN, PAUL JAMES, EDGERTON, MIRA · 2013 to 2017
$1.9M
Circular Dichroism Spectropolarimeter with fluorescence acquisition and temperatuS10RR027232 · NCRR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI STRAUBINGER, ROBERT M · 2010 to 2010
$132k
NCRR NIH HHS S10 RR027232NCRR NIH HHS S10RR027232NIDCR NIH HHS R01 DE010641NIDCR NIH HHS R01DE010641NIDCR NIH HHS R01 DE022720NIDCR NIH HHS R01DE022720NIDCR NIH HHS T32 DE023526
6 · The paper itself

Abstract

Salivary protein histatin 5 (Hst 5) is fungicidal toward Candida albicans, the causative agent of oropharyngeal candidiasis. However, its activity in saliva is compromised by salivary protease-mediated degradation and interaction with salivary salts. Hst 5 has also been shown to bind various metals in saliva-namely, Zn, Cu, and Ni. Surprisingly, interactions of Hst 5 with Fe have not been studied, although iron is one of the most abundant metals present in saliva. Using circular dichroism, we show that Hst 5 can bind up to 10 equivalents of iron as measured by loss of its alpha-helical secondary structure that is normally observed for it in trifluoroethylene. A significant decrease in the candidacidal ability of Hst 5 was observed upon iron binding, with increasing iron concentrations being inversely proportional to Hst 5 killing activity. Binding assays showed that the decrease in killing was likely a result of reduced binding (10-fold reduction) of Fe-Hst 5 to C. albicans cells. Protease stability analysis showed that Fe-Hst 5 was completely resistant to trypsin digestion. In contrast, zinc binding had limited effects on Hst 5 fungicidal activity or protease susceptibility. RNA sequencing results identified changes in iron uptake genes in Hst 5-treated C. albicans cells. Our findings thus suggest that consequences of Hst 5 binding iron not only affect candidacidal ability and proteolyic stability of Hst 5, but may also contribute to a novel killing mechanism involving interference with cellular iron metabolism.

Indexed as

Antifungal AgentsCandida albicansCell WallCircular DichroismFMN ReductaseGenes, FungalHistatinsHumansIronPeriplasmic Binding ProteinsProtein Structure, SecondarySequence Analysis, RNATrypsinZincAntifungal Agentsferric citrate iron reductaseFMN ReductaseHistatinsHTN3 protein, humanIronPeriplasmic Binding Proteinssfu proteins, Serratia marcescensTrypsinZincantimicrobial peptidesCandida albicansproteolysissalivatransition elementszinc

Identifiers

PMID25365968
PMCPMC4270811
OpenAlexW2030338913

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.