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Development of New Therapeutics Targeting Biofilm Formation by the Opportunistic Pulmonary Pathogens Pseudomonas aeruginosa and Aspergillus Fumigatus

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Technical Report,15 Sep 2016,14 Sep 2017

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Hospital for Sick Children Toronto Canada

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The bacterium Pseudomonas aeurginosa PA and fungus Aspergillus fumigatus AF are common causes of pulmonary disease in immunocompromised patients. During infection, both microorganism form a biofilm, which includes exopolysaccharides Pel and Psl PA or galactosaminogalactan AF. PelA, PslG, Sph3 and Ega3 are recently discovered glycoside hydrolases that disrupt PA and AF biofilms in vitro. Our aim is to demonstrate that these enzymes can be used to impair biofilm formation in the host tissues as well, therefore attenuating the infection. During this reported period, we have demonstrated that, in vitro, the enzymes impair the development of normal biofilm both in static culture and in a fluid biofilm culture system, and that they potentiate the action of antibiotics directed at PA or at AF. We have also demonstrated that, when injected intratracheally in mice, the hydrolases did not induce adverse immune reaction, nor did they induce any tissue damage to the host. Pharmacokinetics of the hydrolases in lungs is being assessed, first results showing that Ega3 and PslG persist longer than 12h and 72h, respectively, while Sph3 and PelA are degraded in under 12h.

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  • Medicine and Medical Research

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