Glycoside hydrolase processing of the Pel polysaccharide alters biofilm biomechanics and Pseudomonas aeruginosa virulence

dc.contributor.authorRazvi, Erumen
dc.contributor.authorWhitfield, Gregory B.en
dc.contributor.authorReichhardt, Courtneyen
dc.contributor.authorDreifus, Julia E.en
dc.contributor.authorWillis, Alexandra R.en
dc.contributor.authorGluscencova, Oxana B.en
dc.contributor.authorGloag, Erin S.en
dc.contributor.authorAwad, Tarek S.en
dc.contributor.authorRich, Jacquelyn D.en
dc.contributor.authorda Silva, Daniel Passosen
dc.contributor.authorBond, Whitneyen
dc.contributor.authorLe Mauff, Francoisen
dc.contributor.authorSheppard, Donald C.en
dc.contributor.authorHatton, Benjamin D.en
dc.contributor.authorStoodley, Paulen
dc.contributor.authorReinke, Aaron W.en
dc.contributor.authorBoulianne, Gabrielle L.en
dc.contributor.authorWozniak, Daniel J.en
dc.contributor.authorHarrison, Joe J.en
dc.contributor.authorParsek, Matthew R.en
dc.contributor.authorHowell, P. Lynneen
dc.date.accessioned2023-03-24T18:52:12Zen
dc.date.available2023-03-24T18:52:12Zen
dc.date.issued2023-02-02en
dc.description.abstractPel exopolysaccharide biosynthetic loci are phylogenetically widespread biofilm matrix determinants in bacteria. In Pseudomonas aeruginosa, Pel is crucial for cell-to-cell interactions and reducing susceptibility to antibiotic and mucolytic treatments. While genes encoding glycoside hydrolases have long been linked to biofilm exopolysaccharide biosynthesis, their physiological role in biofilm development is unclear. Here we demonstrate that the glycoside hydrolase activity of P. aeruginosa PelA decreases adherent biofilm biomass and is responsible for generating the low molecular weight secreted form of the Pel exopolysaccharide. We show that the generation of secreted Pel contributes to the biomechanical properties of the biofilm and decreases the virulence of P. aeruginosa in Caenorhabditis elegans and Drosophila melanogaster. Our results reveal that glycoside hydrolases found in exopolysaccharide biosynthetic systems can help shape the soft matter attributes of a biofilm and propose that secreted matrix components be referred to as matrix associated to better reflect their influence.en
dc.description.notesThe authors thank Ira Lacdao and Piyanka Sivarajah for providing recombinantly expressed and purified PelAhPa (PelA 47-303), Dr. K.G. Iliadi for help with Drosophila lifespan and statistical analyses, and Andreea A. Gheorghita for helpful discussions. We thank the following sources of funding: P. Lynne Howell: Canadian Institutes of Health Research (CIHR) MOP 43998 and FDN154327. PLH was the recipient of a Tier I Canada Research Chair (2006-2020). JJH is supported by a Tier II Canada Research Chair from CIHR (2013-2023) and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada. This research has been supported by graduate scholarships from Cystic Fibrosis Canada (GBW) and the Natural Science and Engineering Research Council of Canada (GBW). CR was supported by a K99 Pathway to Independence Award (5K99GM134121-02) and a Postdoc-to-Faculty Transition Award from the Cystic Fibrosis Foundation (REICHH19F5). C. elegans work by ARW and AWR was supported by the Natural Sciences and Engineering Research Council of Canada (Grant #522691522691). Drosophila work by OBG and GLB was supported by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-04119). Erin S. Gloag was funded by an American Heart Association Career Development Award (19CDA34630005).en
dc.description.sponsorshipCanadian Institutes of Health Research (CIHR) [MOP 43998, FDN154327]; Tier I Canada Research Chair; Tier II Canada Research Chair from CIHR; Natural Sciences and Engineering Research Council (NSERC) of Canada; Cystic Fibrosis Canada; Natural Science and Engineering Research Council of Canada [522691522691, RGPIN-2019-04119]; K99 Pathway to Independence Award [5K99GM134121-02]; Cystic Fibrosis Foundation [REICHH19F5]; American Heart Association Career Development Award [19CDA34630005]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41522-023-00375-7en
dc.identifier.eissn2055-5008en
dc.identifier.issue1en
dc.identifier.other7en
dc.identifier.pmid36732330en
dc.identifier.urihttp://hdl.handle.net/10919/114175en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherNature Portfolioen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectGram-negative bacteriaen
dc.subjectcaenorhabditis-elegansen
dc.subjectouter-membraneen
dc.subjectgenesen
dc.subjectalginateen
dc.subjectmatrixen
dc.subjectpa14en
dc.subjectdnaen
dc.subjectdisruptionen
dc.subjectresistanceen
dc.titleGlycoside hydrolase processing of the Pel polysaccharide alters biofilm biomechanics and Pseudomonas aeruginosa virulenceen
dc.title.serialNpj Biofilms and Microbiomesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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