Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis

The Journal of Infectious Diseases
Mark P RoganNoel G McElvaney

Abstract

Intractable formation of biofilm by and infection with the opportunistic pathogen Pseudomonas aeruginosa are hallmarks of cystic fibrosis (CF). Lactoferrin, an innate immunity protein, has recently been shown to inhibit the formation of P. aeruginosa biofilm. Partial cleavage of lactoferrin by the proteases neutrophil elastase and Pseudomonas elastase has previously been described in CF. Here, we show that cathepsins in CF secretions are responsible for complete and rapid cleavage of lactoferrin. We demonstrate that levels of lactoferrin in P. aeruginosa-positive sputum samples are decreased when corrected for inflammatory burden and that P. aeruginosa-positive sputum samples have significantly higher cathepsin activity and significantly reduced ability to inhibit formation of biofilm, compared with P. aeruginosa-negative sputum samples. We also show that cleavage of lactoferrin by cathepsin results in loss of both its microbicidal and antibiofilm activity. Loss of such a vital innate immunity protein clearly has important implications for the pathogenesis of chronic P. aeruginosa lung infection in patients with CF.

Citations

Feb 12, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Elaine HayesEmer P Reeves
Jan 29, 2013·Journal of Wound, Ostomy, and Continence Nursing : Official Publication of the Wound, Ostomy and Continence Nurses Society·Beth Hawkins Bradley, Muriel Cunningham
May 20, 2009·Antimicrobial Agents and Chemotherapy·Hiroyuki WakabayashiHiromasa Yoshie
Mar 25, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sophie Moreau-MarquisBruce A Stanton
Feb 8, 2005·American Journal of Respiratory and Critical Care Medicine·Clifford C TaggartNoel G McElvaney
Nov 19, 2005·American Journal of Respiratory Cell and Molecular Biology·Theo J MoraesGregory P Downey
Mar 17, 2007·The Journal of Clinical Investigation·Yukihiro KanekoPradeep K Singh
Mar 1, 2006·Respiratory Research·Mark P RoganNoel G McElvaney
Jan 11, 2007·Pediatric Research·Julia SedorThomas Ferkol
Oct 30, 2010·Paediatric Drugs·Mireille van Westreenen, Harm A W M Tiddens
May 8, 2010·The Open Respiratory Medicine Journal·Derek J QuinnClifford C Taggart
Jun 19, 2014·American Journal of Respiratory and Critical Care Medicine·Sinéad WeldonClifford C Taggart
Feb 10, 2016·Clinics in Chest Medicine·Emanuela M Bruscia, Tracey L Bonfield
Jun 19, 2008·Drug Discovery Today. Disease Mechanisms·Mark T Clunes, Richard C Boucher
Oct 23, 2009·British Journal of Pharmacology·Catherine M Greene, Noel G McElvaney
Mar 17, 2016·Antioxidants & Redox Signaling·Sylvain MayeurEmile Levy
Jul 16, 2010·Pediatric Pulmonology·S L MartinJ S Elborn
Jun 14, 2005·Medical Hypotheses·Michael P Sherman, Karel Petrak
Feb 25, 2014·The International Journal of Biochemistry & Cell Biology·Abigail R Berkebile, Paul B McCray
Jan 23, 2008·Expert Opinion on Therapeutic Targets·Emer KellyNoel G McElvaney
Jul 18, 2015·Mediators of Inflammation·Matthew S TwiggSinéad Weldon
Oct 16, 2014·American Journal of Respiratory Cell and Molecular Biology·Nicholas W KeiserJohn F Engelhardt
May 28, 2013·The International Journal of Biochemistry & Cell Biology·Fabien LecailleGilles Lalmanach
Mar 15, 2014·The International Journal of Biochemistry & Cell Biology·Sanjay H Chotirmall, Noel G McElvaney
Jan 10, 2012·Biochimica Et Biophysica Acta·Francesco GalliUNKNOWN Working Group on Inflammation in Cystic Fibrosis
May 30, 2016·Applied Microbiology and Biotechnology·Angela T Nguyen, Amanda G Oglesby-Sherrouse
Aug 27, 2016·Annals of the American Thoracic Society·Cormac McCarthyNoel G McElvaney
Sep 16, 2016·International Journal of Pharmaceutics·Lindsay J MarshallJagdeep Shur
Oct 28, 2016·Current Microbiology·Manaf AlMatarBegüm Kayar
Mar 4, 2017·International Journal of Molecular Sciences·Maria Elisa Drago-SerranoMireya de la Garza
Apr 22, 2017·Frontiers in Cellular and Infection Microbiology·Saira R Martínez-AlemánAlejandro Sánchez-González
Sep 16, 2017·International Journal of Molecular Sciences·Luigi RosaPiera Valenti
Dec 21, 2017·Respiratory Research·Andrea GramegnaFrancesco Blasi
Jul 15, 2017·American Journal of Respiratory Cell and Molecular Biology·Oula KhourySean V Murphy

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