Pseudomonas aeruginosa Keratitis: Protease IV and PASP as Corneal Virulence Mediators

<i>Pseudomonas aeruginosa</i> 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 <i>Pseudomonas</i> protease activities, including both <i>Pseudomonas</i> protease IV (PIV) and the <i>P. aeruginosa</i> 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 <i>Pseudomonas putida</i> acquired corneal virulence when it produced active PIV from a plasmid-borne <i>piv</i> 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 <i>P. aeruginosa</i> 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. <i>Pseudomonas</i>-secreted proteases contribute importantly to infections of the cornea, mammalian lung, insects, and plants.