Cell envelope proteases and peptidases of Pseudomonas aeruginosa: multiple roles, multiple mechanisms.

Pseudomonas aeruginosa is a Gram-negative bacterium that is commonly isolated from damp environments. It is also a major opportunistic pathogen, causing a wide range of problematic infections. The cell envelope of P. aeruginosa, comprising the cytoplasmic membrane, periplasmic space, peptidoglycan layer and outer membrane, is critical to the bacteria's ability to adapt and thrive in a wide range of environments. Over 40 proteases and peptidases are located in the P. aeruginosa cell envelope. These enzymes play many crucial roles. They are required for protein secretion out of the cytoplasm to the periplasm, outer membrane, cell surface or the environment; for protein quality control and removal of misfolded proteins; for controlling gene expression, allowing adaptation to environmental changes; for modification and remodelling of peptidoglycan; and for metabolism of small molecules. The key roles of cell envelope proteases in ensuring normal cell functioning have prompted the development of inhibitors targeting some of these enzymes as potential new anti-Pseudomonas therapies. In this review, we summarise the current state of knowledge across the breadth of P. aeruginosa cell envelope proteases and peptidases, with an emphasis on recent findings, and highlight likely future directions in their study.