Novel Entries in a Fungal Biofilm Matrix Encyclopedia

ABSTRACT Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. In this study, we provid...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Robert Zarnowski, William M. Westler, Ghislain Ade Lacmbouh, Jane M. Marita, Jameson R. Bothe, Jörg Bernhardt, Anissa Lounes-Hadj Sahraoui, Joël Fontaine, Hiram Sanchez, Ronald D. Hatfield, James M. Ntambi, Jeniel E. Nett, Aaron P. Mitchell, David R. Andes
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b01789ea810348e691a8c1064b7ff2c5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b01789ea810348e691a8c1064b7ff2c5
record_format	dspace
spelling	oai:doaj.org-article:b01789ea810348e691a8c1064b7ff2c52021-11-15T15:47:22ZNovel Entries in a Fungal Biofilm Matrix Encyclopedia10.1128/mBio.01333-142150-7511https://doaj.org/article/b01789ea810348e691a8c1064b7ff2c52014-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01333-14https://doaj.org/toc/2150-7511ABSTRACT Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. We further explore the function of matrix components, including the impact on drug resistance. We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. Three individual polysaccharides were identified and were suggested to interact physically. Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). Functional matrix proteomic analysis revealed 458 distinct activities. The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. IMPORTANCE This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle.Robert ZarnowskiWilliam M. WestlerGhislain Ade LacmbouhJane M. MaritaJameson R. BotheJörg BernhardtAnissa Lounes-Hadj SahraouiJoël FontaineHiram SanchezRonald D. HatfieldJames M. NtambiJeniel E. NettAaron P. MitchellDavid R. AndesAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 4 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Robert Zarnowski William M. Westler Ghislain Ade Lacmbouh Jane M. Marita Jameson R. Bothe Jörg Bernhardt Anissa Lounes-Hadj Sahraoui Joël Fontaine Hiram Sanchez Ronald D. Hatfield James M. Ntambi Jeniel E. Nett Aaron P. Mitchell David R. Andes Novel Entries in a Fungal Biofilm Matrix Encyclopedia
description	ABSTRACT Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. In this study, we provide a comprehensive analysis of the matrix manufactured by Candida albicans both in vitro and in a clinical niche animal model. We further explore the function of matrix components, including the impact on drug resistance. We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C. albicans biofilm matrix. Three individual polysaccharides were identified and were suggested to interact physically. Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). Functional matrix proteomic analysis revealed 458 distinct activities. The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. IMPORTANCE This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle.
format	article
author	Robert Zarnowski William M. Westler Ghislain Ade Lacmbouh Jane M. Marita Jameson R. Bothe Jörg Bernhardt Anissa Lounes-Hadj Sahraoui Joël Fontaine Hiram Sanchez Ronald D. Hatfield James M. Ntambi Jeniel E. Nett Aaron P. Mitchell David R. Andes
author_facet	Robert Zarnowski William M. Westler Ghislain Ade Lacmbouh Jane M. Marita Jameson R. Bothe Jörg Bernhardt Anissa Lounes-Hadj Sahraoui Joël Fontaine Hiram Sanchez Ronald D. Hatfield James M. Ntambi Jeniel E. Nett Aaron P. Mitchell David R. Andes
author_sort	Robert Zarnowski
title	Novel Entries in a Fungal Biofilm Matrix Encyclopedia
title_short	Novel Entries in a Fungal Biofilm Matrix Encyclopedia
title_full	Novel Entries in a Fungal Biofilm Matrix Encyclopedia
title_fullStr	Novel Entries in a Fungal Biofilm Matrix Encyclopedia
title_full_unstemmed	Novel Entries in a Fungal Biofilm Matrix Encyclopedia
title_sort	novel entries in a fungal biofilm matrix encyclopedia
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/b01789ea810348e691a8c1064b7ff2c5
work_keys_str_mv	AT robertzarnowski novelentriesinafungalbiofilmmatrixencyclopedia AT williammwestler novelentriesinafungalbiofilmmatrixencyclopedia AT ghislainadelacmbouh novelentriesinafungalbiofilmmatrixencyclopedia AT janemmarita novelentriesinafungalbiofilmmatrixencyclopedia AT jamesonrbothe novelentriesinafungalbiofilmmatrixencyclopedia AT jorgbernhardt novelentriesinafungalbiofilmmatrixencyclopedia AT anissalouneshadjsahraoui novelentriesinafungalbiofilmmatrixencyclopedia AT joelfontaine novelentriesinafungalbiofilmmatrixencyclopedia AT hiramsanchez novelentriesinafungalbiofilmmatrixencyclopedia AT ronalddhatfield novelentriesinafungalbiofilmmatrixencyclopedia AT jamesmntambi novelentriesinafungalbiofilmmatrixencyclopedia AT jenielenett novelentriesinafungalbiofilmmatrixencyclopedia AT aaronpmitchell novelentriesinafungalbiofilmmatrixencyclopedia AT davidrandes novelentriesinafungalbiofilmmatrixencyclopedia
_version_	1718427540165492736

Novel Entries in a Fungal Biofilm Matrix Encyclopedia

Ejemplares similares