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

Ajitha Thanabalasuriar1, Brittney Noelle Vivian Scott2, Moritz Peiseler2

  • 1University of Calgary, Department of Physiology and Pharmacology, Calvin Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, Calgary, AB, Canada; Microbial Sciences, MedImmune/AstraZeneca LLC, Gaithersburg, MD, USA.

Cell Host & Microbe
|April 2, 2019
PubMed

Insights

Pseudomonas aeruginosa biofilms cause intractable bacterial keratitis. Blocking Psl and type-3 secretion systems (T3SS) with antibiotics clears biofilms and reverses eye infection.

Area of Science:

  • Microbiology
  • Immunology
  • Ophthalmology

Background:

  • Bacterial biofilm infections, particularly Pseudomonas aeruginosa keratitis, are challenging due to antibiotic resistance and recurrence.
  • The Psl exopolysaccharide and type-3 secretion system (T3SS) of P. aeruginosa contribute to biofilm formation and virulence.
  • Neutrophil extracellular traps (NETs) play a role in limiting bacterial spread during ocular infections.

Purpose of the Study:

  • To investigate the role of neutrophils and NETosis in controlling P. aeruginosa corneal biofilms.
  • To explore the potential of targeting Psl and T3SS for treating bacterial keratitis.

Main Methods:

  • Intravital microscopy was used to observe neutrophil recruitment and behavior in P. aeruginosa corneal infections.
  • Analysis of Psl and T3SS expression in biofilms.
  • Evaluation of combined therapeutic strategies including antibiotics, Psl inhibition, and T3SS inhibition.

Main Results:

  • Neutrophils were recruited to corneal infections and underwent NETosis at the base of P. aeruginosa biofilms, driven by T3SS expression.
  • NETs formed a barrier that confined biofilms to the ocular surface, preventing dissemination.
  • Established biofilms were resistant to antibiotics and neutrophil killing, leading to disease progression.
  • Combined blockade of Psl and T3SS with antibiotics effectively eradicated biofilms and reversed keratitis.

Conclusions:

  • Neutrophil recruitment and NETosis are crucial in limiting the spread of P. aeruginosa keratitis.
  • Targeting both Psl and T3SS, in conjunction with antibiotics, represents a promising therapeutic strategy for intractable bacterial keratitis.
Keywords:
P. aeruginosabiofilmscorneaintravital microscopykeratitisneutrophil extracellular traps

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