Intracellular Pseudomonas aeruginosa persist and evade antibiotic treatment in a wound infection model.
St��phane Pont, Flore Nilly, Laurence Berry, Anne Bonhoure, Morgan A Alford, M��lissande Louis, Pauline Nogaret, Manjeet Bains, Olivier Lesouhaitier, Robert E W Hancock, Patrick Pl��siat, Anne-B��atrice Blanc-Potard
Author Information
St��phane Pont: Laboratory of Pathogens and Host Immunity (LPHI), Universit�� de Montpellier, CNRS, Inserm, 34095, Montpellier, France.
Flore Nilly: Laboratory of Pathogens and Host Immunity (LPHI), Universit�� de Montpellier, CNRS, Inserm, 34095, Montpellier, France.
Laurence Berry: Laboratory of Pathogens and Host Immunity (LPHI), Universit�� de Montpellier, CNRS, Inserm, 34095, Montpellier, France.
Anne Bonhoure: Laboratory of Pathogens and Host Immunity (LPHI), Universit�� de Montpellier, CNRS, Inserm, 34095, Montpellier, France.
Morgan A Alford: Center for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada.
M��lissande Louis: CBSA UR4312, Laboratoire de microbiologie Communication Bact��rienne et Strat��gies Anti-Infectieuses, Univ Rouen Normandie, Universit�� Caen Normandie, Normandie Univ, Rouen, France.
Pauline Nogaret: Laboratory of Pathogens and Host Immunity (LPHI), Universit�� de Montpellier, CNRS, Inserm, 34095, Montpellier, France.
Manjeet Bains: Center for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada.
Olivier Lesouhaitier: CBSA UR4312, Laboratoire de microbiologie Communication Bact��rienne et Strat��gies Anti-Infectieuses, Univ Rouen Normandie, Universit�� Caen Normandie, Normandie Univ, Rouen, France.
Robert E W Hancock: Center for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada.
Patrick Pl��siat: UMR6249 CNRS Chrono-environnement, Universit�� de Franche-Comt��, Besan��on, France.
Anne-B��atrice Blanc-Potard: Laboratory of Pathogens and Host Immunity (LPHI), Universit�� de Montpellier, CNRS, Inserm, 34095, Montpellier, France. ORCID
Persistent bacterial infections evade host immunity and resist antibiotic treatments through various mechanisms that are difficult to evaluate in a living host. Pseudomonas aeruginosa is a main cause of chronic infections in patients with cystic fibrosis (CF) and wounds. Here, by immersing wounded zebrafish embryos in a suspension of P. aeruginosa isolates from CFpatients, we established a model of persistent infection that mimics a murine chronic skin infection model. Live and electron microscopy revealed persisting aggregated P. aeruginosa inside zebrafish cells, including macrophages, at unprecedented resolution. Persistent P. aeruginosa exhibited adaptive resistance to several antibiotics, host cell permeable drugs being the most efficient. Moreover, persistent bacteria could be partly re-sensitized to antibiotics upon addition of anti-biofilm molecules that dispersed the bacterial aggregates in vivo. Collectively, this study demonstrates that an intracellular location protects persistent P. aeruginosa in vivo in wounded zebrafish embryos from host innate immunity and antibiotics, and provides new insights into efficient treatments against chronic infections.
