{"id":791,"date":"2016-01-05T15:14:31","date_gmt":"2016-01-05T20:14:31","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/howell\/?page_id=791"},"modified":"2024-02-26T15:49:21","modified_gmt":"2024-02-26T20:49:21","slug":"glycoside-hydrolases","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/howell\/research\/glycoside-hydrolases\/","title":{"rendered":"Glycoside hydrolases"},"content":{"rendered":"<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 hundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-overflow:visible;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-one-full fusion-column-first fusion-column-last fusion-column-no-min-height\" style=\"--awb-bg-size:cover;--awb-margin-bottom:0px;\"><div class=\"fusion-column-wrapper fusion-flex-column-wrapper-legacy\"><div class=\"fusion-text fusion-text-1\"><p>In collaboration with labs in Canada and the United States, our lab is developing therapeutic enzymatic compositions (glycoside hydrolases) for degrading and inhibiting production of bacterial and fungal biofilms.<a href=\"https:\/\/lab.research.sickkids.ca\/howell\/wp-content\/uploads\/sites\/17\/2015\/11\/Biofilm-Treatment.jpg\" rel=\"attachment wp-att-793\"><img decoding=\"async\" class=\"aligncenter size-full wp-image-793\" src=\"https:\/\/lab.research.sickkids.ca\/howell\/wp-content\/uploads\/sites\/17\/2015\/11\/Biofilm-Treatment.jpg\" alt=\"Schematic of biofilm treatment\" width=\"965\" height=\"195\" srcset=\"https:\/\/lab.research.sickkids.ca\/howell\/wp-content\/uploads\/sites\/17\/2015\/11\/Biofilm-Treatment-300x61.jpg 300w, https:\/\/lab.research.sickkids.ca\/howell\/wp-content\/uploads\/sites\/17\/2015\/11\/Biofilm-Treatment-768x155.jpg 768w, https:\/\/lab.research.sickkids.ca\/howell\/wp-content\/uploads\/sites\/17\/2015\/11\/Biofilm-Treatment.jpg 965w\" sizes=\"(max-width: 965px) 100vw, 965px\" \/><\/a><\/p>\n<p class=\"p1\">The glycoside hydrolase domains of (PslG, PelA\u00a0and Sph3) explicitly target and degrade the exopolysaccharides Psl, Pel, and galactosaminogalactan (GAG), respectively. These polysaccharides are used by <em>Pseudomonas<\/em>\u00a0spp and the fungus <em>Aspergillus\u00a0fumigatus<\/em> in pathogenesis. As such, we are developing these hydrolases as therapeutics for the treatment of infections caused by these organisms. The specificity of the enzymes allows for selective disruption of the biofilm through the hydrolysis of its exopolysaccharide(s). The enzymes potentiate antimicrobials and the innate immune response, can prevent biofilm growth for extended periods of time, and have no effect on mammalian cell viability.<\/p>\n<h2>Potential applications<\/h2>\n<p>Current findings create a promising avenue for the development of these enzymes as:<\/p>\n<ul>\n<li>Novel therapeutics for the treatment of a wide variety of chronic infections, including pulmonary infections in patients with chronic lung diseases (pneumonia, invasive aspergillosis, and whooping cough), and infections of chronic wounds and burns which affect 1-2 per cent of the world\u2019s population.<\/li>\n<li>Disinfectants and coatings for protecting surfaces including, but not limited to medical devices, catheters, implants and non-medical applications such as marine antifouling applications.<\/li>\n<li>Biologics for protecting crops from fungal diseases.<\/li>\n<\/ul>\n<\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-bottom:20px;width:100%;\"><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-text fusion-text-2\"><h2>Publications<\/h2>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35005941\/\">Preventing\u00a0<i>Pseudomonas aeruginosa<\/i> Biofilms on Indwelling Catheters by Surface-Bound Enzymes.<\/a> Asker D, Awad TS, Raju D, Sanchez H, Lacdao I, Gilbert S, Sivarajah P, Andes DR, Sheppard DC, Howell PL, Hatton BD. \u00a0ACS Appl Bio Mater. 2021 Dec 20;4(12):8248-8258. doi: 10.1021\/acsabm.1c00794.<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34579578\/\">Preclinical Evaluation of Recombinant Microbial Glycoside Hydrolases in the Prevention of Experimental Invasive Aspergillosis.<\/a> Ostapska H, Raju D, Lehoux M, Lacdao I, Gilbert S, Sivarajah P, Bamford NC, Baker P, Nguyen TTM, Zacharias CA, Gravelat FN, Howell PL, Sheppard DC.\u00a0 mBio. 2021 Oct 26;12(5):e0244621. doi: 10.1128\/mBio.02446-21.<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/30988141\/\">Treatment with the Pseudomonas aeruginosa Glycoside Hydrolase PslG Combats Wound Infection by Improving Antibiotic Efficacy and Host Innate Immune Activity.<\/a> Pestrak MJ, Baker P, Dellos-Nolan S, Hill PJ, Passos da Silva D, Silver H, Lacdao I, Raju D, Parsek MR, Wozniak DJ, Howell PL. Antimicrob Agents Chemother. 2019 May 24;63(6):e00234-19. doi: 10.1128\/AAC.00234-19.<\/p>\n<p class=\"title\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29571052\">Non-eluting, surface-bound enzymes disrupt surface attachment of bacteria by continuous biofilm polysaccharide degradation.<\/a> Asker D, Awad TS, Baker P,\u00a0Howell PL, Hatton BD.\u00a0<span class=\"jrnl\" title=\"Biomaterials\">Biomaterials<\/span>. 2018 Jun;167:168-176. doi: 10.1016\/j.biomaterials.2018.03.016.<\/p>\n<p class=\"title\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27386527\">Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms.<\/a> Baker P, Hill PJ, Snarr BD, Alnabelseya N, Pestrak MJ, Lee MJ, Jennings LK, Tam J, Melnyk RA, Parsek MR, Sheppard DC, Wozniak DJ,\u00a0Howell PL.\u00a0<span class=\"jrnl\" title=\"Science advances\">Sci Adv<\/span>. 2016 May 20;2(5):e1501632. doi: 10.1126\/sciadv.1501632.<\/p>\n<h2>Patents<\/h2>\n<p><span class=\"ui-provider ed bug buh bui buj buk bul bum bun buo bup buq bur bus but buu buv buw bux buy buz bva bvb bvc bvd bve bvf bvg bvh bvi bvj bvk bvl bvm bvn\" dir=\"ltr\"><a href=\"https:\/\/patents.google.com\/patent\/EP3152303B1\/en?oq=3152303\">Soluble bacterial and fungal proteins and methods and uses thereof in inhibiting and dispersing biofilm.<\/a> European Patent, 3152303, Granted November 24, 2021.<\/span><\/p>\n<p><span class=\"ui-provider ed bug buh bui buj buk bul bum bun buo bup buq bur bus but buu buv buw bux buy buz bva bvb bvc bvd bve bvf bvg bvh bvi bvj bvk bvl bvm bvn\" dir=\"ltr\"><a href=\"https:\/\/patents.google.com\/patent\/AU2015271666B2\/en?oq=2015271666\">Soluble bacterial and fungal proteins and methods and uses thereof in inhibiting and dispersing biofilm.<\/a> Australian Patent 2015271666, Granted June 18, 2021.\u2003<\/span><\/p>\n<p><span class=\"ui-provider ed bug buh bui buj buk bul bum bun buo bup buq bur bus but buu buv buw bux buy buz bva bvb bvc bvd bve bvf bvg bvh bvi bvj bvk bvl bvm bvn\" dir=\"ltr\"><a href=\"https:\/\/patents.google.com\/patent\/US20210138044A1\/en?oq=US2021%2f0138044\">Soluble bacterial and fungal proteins and methods and uses thereof in inhibiting and dispersing biofilm.<\/a> US Patent US2021\/0138044, Published May 13, 2021.<\/span><\/p>\n<\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":1013,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-791","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.0 (Yoast SEO v27.0) - 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