Pyocycanin, a contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lung

2015
journal article
article
dc.abstract.enSeveral recent studies show that the lungs infected with Pseudomonas aeruginosa are often co-colonised by oral bacteria including black-pigmenting anaerobic (BPA) Porphyromonas species. The BPAs have an absolute haem requirement and their presence in the infected lung indicates that sufficient haem, a virulence up-regulator in BPAs, must be present to support growth. Haemoglobin from micro-bleeds occurring during infection is the most likely source of haem in the lung. Porphyromonas gingivalis displays a novel haem acquisition paradigm whereby haemoglobin must be firstly oxidised to methaemoglobin, facilitating haem release, either by gingipain proteolysis or capture via the haem-binding haemophore HmuY. P. aeruginosa produces the blue phenazine redox compound, pyocyanin. Since phenazines can oxidise haemoglobin, it follows that pyocyanin may also facilitate haem acquisition by promoting methaemoglobin production. Here we show that pyocyanin at concentrations found in the CF lung during P. aeruginosa infections rapidly oxidises oxyhaemoglobin in a dose-dependent manner. We demonstrate that methaemoglobin formed by pyocyanin is also susceptible to proteolysis by P. gingivalis Kgp gingipain and neutrophil elastase, thus releasing haem. Importantly, co-incubation of oxyhaemoglobin with pyocyanin facilitates haem pickup from the resulting methemoglobin by the P. gingivalis HmuY haemophore. Mice intra-tracheally challenged with viable P. gingivalis cells plus pyocyanin displayed increased mortality compared to those administered P. gingivalis alone. Pyocyanin significantly elevated both methaemoglobin and total haem levels in homogenates of mouse lungs and increased the level of arginine-specific gingipain activity from mice inoculated with viable P. gingivalis cells plus pyocyanin compared with mice inoculated with P. gingivalis only. These findings indicate that pyocyanin, by promoting haem availability through methaemoglobin formation and stimulating of gingipain production, may contribute to virulence of P. gingivalis and disease severity when co-infecting with P. aeruginosa in the lung.pl
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologiipl
dc.contributor.authorBenedyk-Machaczka, Małgorzata - 200072 pl
dc.contributor.authorByrne, Dominic P.pl
dc.contributor.authorCiastoń, Izabela - 163063 pl
dc.contributor.authorPotempa, Jan - 131531 pl
dc.contributor.authorOlczak, Mariuszpl
dc.contributor.authorOlczak, Teresapl
dc.contributor.authorSmalley, John W.pl
dc.date.accessioned2015-05-28T09:42:15Z
dc.date.available2015-05-28T09:42:15Z
dc.date.issued2015pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.additionalCorrection: PLoS ONE, 2016, Vol. 11 (1) : e0148008, DOI: 10.1371/journal.pone.0148008. Izabela Ciastoń podpisana jako Izabela Glowczyk; Małgorzata Benedyk-Machaczka podpisana jako Malgorzata Benedykpl
dc.description.number2pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume10pl
dc.identifier.articleide0118319pl
dc.identifier.doi10.1371/journal.pone.0118319pl
dc.identifier.eissn1932-6203pl
dc.identifier.projectROD UJ / Ppl
dc.identifier.urihttp://ruj.uj.edu.pl/xmlui/handle/item/8342
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeotwarte czasopismo
dc.subtypeArticlepl
dc.titlePyocycanin, a contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lungpl
dc.title.alternativePyocyanin, a contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lungpl
dc.title.journalPLoS ONEpl
dc.typeJournalArticlepl
dspace.entity.typePublication

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