Treatment with the Pseudomonas aeruginosa Glycoside Hydrolase PslG Combats Wound Infection by Improving Antibiotic Efficacy and Host Innate Immune Activity

is an opportunistic, nosocomial bacterial pathogen that forms persistent infections due to the formation of protective communities, known as biofilms. Once the biofilm is formed, the bacteria embedded within it are recalcitrant to antimicrobial treatment and host immune defenses. Moreover, the prese...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2019-06, Vol.63 (6)
Main Authors: Pestrak, Matthew J, Baker, Perrin, Dellos-Nolan, Sheri, Hill, Preston J, Passos da Silva, Daniel, Silver, Holly, Lacdao, Ira, Raju, Deepa, Parsek, Matthew R, Wozniak, Daniel J, Howell, P Lynne
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents
Anti-Bacterial Agents - pharmacology
Biofilms - drug effects
Experimental Therapeutics
Female
Glycoside Hydrolases
Glycoside Hydrolases - pharmacology
Humans
Immunity, Innate
Immunity, Innate - drug effects
Mice
Mice, Inbred BALB C
Neutrophils - drug effects
Neutrophils - metabolism
Phagocytosis - drug effects
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas Infections - drug therapy
Pseudomonas Infections - metabolism
Reactive Oxygen Species - metabolism
Swine
Tobramycin - pharmacology
Wound Infection
Wound Infection - drug therapy
Wound Infection - metabolism
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Summary:is an opportunistic, nosocomial bacterial pathogen that forms persistent infections due to the formation of protective communities, known as biofilms. Once the biofilm is formed, the bacteria embedded within it are recalcitrant to antimicrobial treatment and host immune defenses. Moreover, the presence of biofilms in wounds is correlated with chronic infection and delayed healing. The current standard of care for chronic wound infections typically involves physical disruption of the biofilm via debridement and subsequent antimicrobial treatment. The glycoside hydrolases PelA and PslG have been demonstrated to disrupt biofilm integrity through degradation of the key biofilm matrix exopolysaccharides Pel and Psl, respectively. Herein, we demonstrate that PslG hydrolase therapy is a promising strategy for controlling wound infections. Hydrolase treatment of biofilms resulted in increased antibiotic efficacy and penetration into the biofilm. PslG treatment of biofilms also improved innate immune activity leading to greater complement deposition, neutrophil phagocytosis, and neutrophil reactive oxygen species production. Furthermore, when -infected wounds were treated with a combination of PslG and tobramycin, we observed an additive effect leading to greater bacterial clearance than treatments of tobramycin or PslG alone. This study demonstrates that PelA and PslG have promising therapeutic potential and that PslG may aid in the treatment of wound infections.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00234-19