Abstract
Pseudomonas aeruginosa is a leading cause of bacterial keratitis, especially in users of contact lenses. These infections are characterized by extensive degradation of the corneal tissue mediated by Pseudomonas protease activities, including both Pseudomonas protease IV (PIV) and the P. aeruginosa small protease (PASP). The virulence role of PIV was determined by the reduced virulence of a PIV-deficient mutant relative to its parent strain and the mutant after genetic complementation (rescue). Additionally, the non-ocular pathogen Pseudomonas putida acquired corneal virulence when it produced active PIV from a plasmid-borne piv gene. The virulence of PIV is not limited to the mammalian cornea, as evidenced by its destruction of respiratory surfactant proteins and the cytokine interleukin-22 (IL-22), the key inducer of anti-bacterial peptides. Furthermore, PIV contributes to the P. aeruginosa infection of both insects and plants. A possible limitation of PIV is its inefficient digestion of collagens; however, PASP, in addition to cleaving multiple soluble proteins, is able to efficiently cleave collagens. A PASP-deficient mutant lacks the corneal virulence of its parent or rescue strain evidencing its contribution to corneal damage, especially epithelial erosion. Pseudomonas-secreted proteases contribute importantly to infections of the cornea, mammalian lung, insects, and plants.
Highlights
Pseudomonas aeruginosa Keratitis and the Role of the Secreted ProteasesPseudomonas aeruginosa causes infections in animals ranging from mammals to insects, and in plants
P. aeruginosa keratitis is characterized by the development of corneal ulcers and, even with proper antibiotic therapy, has the potential to develop corneal scarring that impairs vision
These findings indicate that protease IV (PIV) auto-processes the proenzyme into the mature protease by cleaving the proenzyme at the lysine found at the junction between the propeptide and the mature protease
Summary
Pseudomonas aeruginosa causes infections in animals ranging from mammals to insects, and in plants. A key objective of research on Pseudomonas keratitis has been the identification of the bacterial products that damage the eye, with a long-term goal of developing means to inhibit the activity of these bacterial products Inhibition of these bacterial pathogenic mechanisms is recognized as a means to treat infections, especially when antibiotic resistance is problematic [6]. In 1958, a study of the P. aeruginosa culture supernatant showed that secreted bacterial products could cause a corneal ulcer in a rabbit eye [9]. This activity was sensitive to heat, suggesting that one or more proteins were the active component. Broad spectrum protease and virulence related Lysine specific and important virulence factor
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