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1.
Infect Immun ; 85(1)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27795361

RESUMO

Pseudomonas aeruginosa is an important opportunistic human pathogen that lives in biofilm-like cell aggregates at sites of chronic infection, such as those that occur in the lungs of patients with cystic fibrosis and nonhealing ulcers. During growth in a biofilm, P. aeruginosa dramatically increases the production of filamentous Pf bacteriophage (Pf phage). Previous work indicated that when in vivo Pf phage production was inhibited, P. aeruginosa was less virulent. However, it is not clear how the production of abundant quantities of Pf phage similar to those produced by biofilms under in vitro conditions affects pathogenesis. Here, using a murine pneumonia model, we show that the production of biofilm-relevant amounts of Pf phage prevents the dissemination of P. aeruginosa from the lung. Furthermore, filamentous phage promoted bacterial adhesion to mucin and inhibited bacterial invasion of airway epithelial cultures, suggesting that Pf phage traps P. aeruginosa within the lung. The in vivo production of Pf phage was also associated with reduced lung injury, reduced neutrophil recruitment, and lower cytokine levels. Additionally, when producing Pf phage, P. aeruginosa was less prone to phagocytosis by macrophages than bacteria not producing Pf phage. Collectively, these data suggest that filamentous Pf phage alters the progression of the inflammatory response and promotes phenotypes typically associated with chronic infection.


Assuntos
Inflamação/microbiologia , Inflamação/virologia , Inovirus/crescimento & desenvolvimento , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/virologia , Pseudomonas aeruginosa/virologia , Animais , Biofilmes/crescimento & desenvolvimento , Fibrose Cística/microbiologia , Fibrose Cística/virologia , Pulmão/microbiologia , Pulmão/virologia , Macrófagos/microbiologia , Macrófagos/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/fisiologia
2.
Cell Host Microbe ; 18(5): 549-59, 2015 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-26567508

RESUMO

Biofilms-communities of bacteria encased in a polymer-rich matrix-confer bacteria with the ability to persist in pathologic host contexts, such as the cystic fibrosis (CF) airways. How bacteria assemble polymers into biofilms is largely unknown. We find that the extracellular matrix produced by Pseudomonas aeruginosa self-assembles into a liquid crystal through entropic interactions between polymers and filamentous Pf bacteriophages, which are long, negatively charged filaments. This liquid crystalline structure enhances biofilm function by increasing adhesion and tolerance to desiccation and antibiotics. Pf bacteriophages are prevalent among P. aeruginosa clinical isolates and were detected in CF sputum. The addition of Pf bacteriophage to sputum polymers or serum was sufficient to drive their rapid assembly into viscous liquid crystals. Fd, a related bacteriophage of Escherichia coli, has similar biofilm-building capabilities. Targeting filamentous bacteriophage or the liquid crystalline organization of the biofilm matrix may represent antibacterial strategies.


Assuntos
Biofilmes/crescimento & desenvolvimento , Inovirus/fisiologia , Polímeros/metabolismo , Fagos de Pseudomonas/fisiologia , Pseudomonas aeruginosa/fisiologia , Pseudomonas aeruginosa/virologia , Aminoglicosídeos/farmacologia , Biofilmes/efeitos dos fármacos , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Humanos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Simbiose
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