Altered distribution of chronicity-deficient Pseudomonas aeruginosa mutant guides optimization of synthetic chronic wound model

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Abstract
Pseudomonas aeruginosa is commonly isolated from chronic wounds where it forms biofilms that are recalcitrant to current treatments, greatly impacting the morbidity and mortality of infected patients. Since P. aeruginosa dictates wound severity and treatment outcomes, this bacterium is an important target in the treatment of chronic wound infections. This study aimed to unravel the functional intricacies of a key virulence factor, the arginine-specific aminopeptidase of P. aeruginosa (AaaA), which is crucial for the establishment and persistence of chronic infections. While interrogation of genomes revealed that aaaA is highly conserved, its activity varied between chronic wound clinical isolates. To explore the phenotypic impact of AaaA in chronic infections, a collagen-based synthetic chronic wound (SCW) model was optimized to enable reproducible assessment of AaaA activity. AaaA activity was increased within the SCW compared to planktonic cultures, further supporting the hypothesis that this virulence factor is integral to chronic infections caused by P. aeruginosa . It was also shown that AaaA contributed to biofilm formation as well as providing a survival advantage within the SCW model. Overall, a novel link between AaaA and biofilm formation was verified and served to guide the optimisation of a realistic chronic wound infection model.
Funding Information
  • European Molecular Biology Organization (10006)
  • Federation of European Microbiological Societies (2669)
  • University of Nottingham
  • Medical Research Council
  • Magle Chemoswed
  • Biotechnology and Biological Sciences Research Council (BB/R012415/1)
  • Wellcome Trust (Antimicrobials and antimicrobial resistance DTP 108876/B/15/Z)

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