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Modulation of Pseudomonas aeruginosa adherence to the corneal surface by mucus
S M Fleiszig1, T S Zaidi, R Ramphal
1Channing Laboratory Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Abstract:
To gain access to the corneal epithelium and cause infections keratitis, bacterial pathogens must first interact with ocular surface factors that could affect bacterial adherence. In this study, we demonstrated that the mucus layer, and, in particular, the mucin fraction of mucus, modulated adherence to intact corneal epithelium of Pseudomonas aeruginosa but not that of Staphylococcus aureus or Streptococcus pyogenes. Removal of endogenous mucus from rat or rabbit eyes increased the adherence of P. aeruginosa by 3- to 10-fold. Ocular mucus obtained from rat eyes, porcine stomach mucin, or bovine submaxillary gland mucin inhibited adherence of P. aeruginosa to uninjured corneal epithelium. The mucin fraction of ocular mucus, purified by ultracentrifugation, was found to contain the inhibitory activity, and inhibition was demonstrated at concentrations of mucin as low as 35 micrograms/ml. Ocular mucin was the only material tested that inhibited adherence of P. aeruginosa to an injured cornea. However, the binding of P. aeruginosa to immobilized substrates in vitro did not predict which fraction would possess antiadherence activity: bacteria bound well to whole ocular mucus, mucin, the nonmucin fraction of ocular mucus, and dilute human tears as well as to porcine stomach mucin and bovine submaxillary gland mucin. The effectiveness of the mucin fraction of ocular mucus at inhibiting the binding of P. aeruginosa to the cornea implies that this material is a barrier that protects the surface of the eye from P. aeruginosa adherence.
Insights
The eye
Area of Science:
- Ocular Microbiology
- Biochemistry
- Immunology
Background:
- Bacterial keratitis is a significant cause of vision loss.
- Bacterial adherence to the corneal epithelium is a critical first step in infection.
- Ocular surface factors, including mucus, may influence bacterial adherence.
Purpose of the Study:
- To investigate the role of the ocular mucus layer in bacterial adherence to the corneal epithelium.
- To determine if mucins within the mucus layer inhibit adherence of key bacterial pathogens.
Main Methods:
- Assessing adherence of Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes to intact and injured corneal epithelium.
- Evaluating the effect of endogenous ocular mucus, purified mucins, and other fractions on bacterial adherence.
- Using in vitro assays to measure bacterial binding to various substrates.
Main Results:
- The mucus layer, specifically its mucin fraction, significantly modulated Pseudomonas aeruginosa adherence to intact corneal epithelium.
- Removal of endogenous mucus increased P. aeruginosa adherence by 3- to 10-fold.
- Ocular mucin, but not other fractions, inhibited P. aeruginosa adherence to both intact and injured corneas.
- Bacterial binding to immobilized substrates did not consistently predict anti-adherence activity.
Conclusions:
- Ocular mucins act as a protective barrier against P. aeruginosa adherence to the cornea.
- Mucins play a crucial role in preventing bacterial keratitis by inhibiting pathogen attachment.
- Targeting mucin-pathogen interactions could offer novel therapeutic strategies for bacterial eye infections.