Details

Autor(en) / Beteiligte

• Thanabalasuriar, Ajitha
• Scott, Brittney Noelle Vivian
• Peiseler, Moritz
• Willson, Michelle Elizabeth
• Zeng, Zhutian
• Warrener, Paul
• Keller, Ashley Elaine
• Surewaard, Bas Gerardus Johannes
• Dozier, Elizabeth Ashley
• Korhonen, Juha Tapio
• Cheng, Lily I-ting
• Gadjeva, Mihaela
• Stover, C. Kendall
• DiGiandomenico, Antonio
• Kubes, Paul

Titel

Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion

Ist Teil von

• Cell host & microbe, 2019-04, Vol.25 (4), p.526-536.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Bacterial biofilm infections are difficult to eradicate because of antibiotic insusceptibility and high recurrence rates. Biofilm formation by Pseudomonas aeruginosa, a leading cause of bacterial keratitis, is facilitated by the bacterial Psl exopolysaccharide and associated with heightened virulence. Using intravital microscopy, we observed that neutrophilic recruitment to corneal infections limits P. aeruginosa biofilms to the outer eye surface, preventing bacterial dissemination. Neutrophils moved to the base of forming biofilms, where they underwent neutrophil extracellular trap formation (NETosis) in response to high expression of the bacterial type-3 secretion system (T3SS). NETs formed a barrier “dead zone,” confining bacteria to the external corneal environment and inhibiting bacterial dissemination into the brain. Once formed, ocular biofilms were resistant to antibiotics and neutrophil killing, advancing eye pathology. However, blocking both Psl and T3SS together with antibiotic treatment broke down the biofilm and reversed keratitis, suggesting future therapeutic strategies for this intractable infection. [Display omitted] •P. aeruginosa keratitis infections result in biofilm formation on the cornea•NETs form at the base of the biofilm, triggered by the type-3 secretion system (T3SS)•NETs stop bacterial dissemination into the brain but promote antibiotic resistance•Blocking exopolysaccharide Psl and the T3SS allowed neutrophils to break down the biofilm Thanabalasuriar et al. characterize the interplay between neutrophils and Pseudomonas biofilms on the cornea. At the base of the biofilm, neutrophils encountered expression of the type-3 secretion system, leading to an expansive deposition of neutrophil extracellular traps (NETs). NET formation impeded bacterial dissemination into the brain yet promoted antibiotic resistance.