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.
The glycoside hydrolase domains of (PslG, PelA and Sph3) explicitly target and degrade the exopolysaccharides Psl, Pel, and galactosaminogalactan (GAG), respectively. These polysaccharides are used by Pseudomonas spp and the fungus Aspergillus fumigatus 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.
Potential applications
Current findings create a promising avenue for the development of these enzymes as:
- 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’s population.
- Disinfectants and coatings for protecting surfaces including, but not limited to medical devices, catheters, implants and non-medical applications such as marine antifouling applications.
- Biologics for protecting crops from fungal diseases.
Publications
Preventing Pseudomonas aeruginosa Biofilms on Indwelling Catheters by Surface-Bound Enzymes. Asker D, Awad TS, Raju D, Sanchez H, Lacdao I, Gilbert S, Sivarajah P, Andes DR, Sheppard DC, Howell PL, Hatton BD. ACS Appl Bio Mater. 2021 Dec 20;4(12):8248-8258. doi: 10.1021/acsabm.1c00794.
Preclinical Evaluation of Recombinant Microbial Glycoside Hydrolases in the Prevention of Experimental Invasive Aspergillosis. 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. mBio. 2021 Oct 26;12(5):e0244621. doi: 10.1128/mBio.02446-21.
Treatment with the Pseudomonas aeruginosa Glycoside Hydrolase PslG Combats Wound Infection by Improving Antibiotic Efficacy and Host Innate Immune Activity. 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.
Non-eluting, surface-bound enzymes disrupt surface attachment of bacteria by continuous biofilm polysaccharide degradation. Asker D, Awad TS, Baker P, Howell PL, Hatton BD. Biomaterials. 2018 Jun;167:168-176. doi: 10.1016/j.biomaterials.2018.03.016.
Exopolysaccharide biosynthetic glycoside hydrolases can be utilized to disrupt and prevent Pseudomonas aeruginosa biofilms. Baker P, Hill PJ, Snarr BD, Alnabelseya N, Pestrak MJ, Lee MJ, Jennings LK, Tam J, Melnyk RA, Parsek MR, Sheppard DC, Wozniak DJ, Howell PL. Sci Adv. 2016 May 20;2(5):e1501632. doi: 10.1126/sciadv.1501632.
Patents
Soluble bacterial and fungal proteins and methods and uses thereof in inhibiting and dispersing biofilm. European Patent, 3152303, Granted November 24, 2021.
Soluble bacterial and fungal proteins and methods and uses thereof in inhibiting and dispersing biofilm. Australian Patent 2015271666, Granted June 18, 2021.
Soluble bacterial and fungal proteins and methods and uses thereof in inhibiting and dispersing biofilm. US Patent US2021/0138044, Published May 13, 2021.