[ATP-dependant proteolysis and bacterial pathogenesis]

Proteolysis plays an central role in key metabolic pathways and cellular adaptation to environmental changes. It modulates the activity of regulatory peptides and eliminates misfolded or damaged proteins such as those generated by stress exposure. In eucaryotic cells ATP- dependent proteolysis is carried out by the 26S proteasome whose substrates are identified by ubiquitin tags. Conversely, bacteria possess several tagging systems and different ATP- dependent proteases. Bacterial ATP-dependent proteases carry distinct chaperone-ATPase and peptidase activities, either on the same molecule or on separate subunits. Although unrelated, all ATP-dependent proteases function according to a similar multistep scheme, from the docking of a substrate by the ATPase region to its proteolysis by the peptidase. Major bacterial ATP- dependent proteases include FtsH, Lon, HslUV and the Clp proteases. Clp proteases are multimeric complexes assembled into a structure centered on the proteolytic component ClpP. They are essential for quick adaptation to stress and regulate important developmental processes. Clp-mediated proteolysis is also required for disease progression and virulence of several bacterial pathogens, favoring survival in the host or modulating the activity of genuine virulence factors.