Secretion Systems as Targets for Th

Secretion Systems as Targets for Therapy Gram-negative bacteria possess protein secretion systems, which are molecular nanomachines spanning the two bacterial membranes to release proteins and enzymes among which are numerous virulence factors (Figure 1). P. aeruginosa harbors five of the so far six known secretion systems in Gram-negative bacteria, termed Type I to Type VI secretion systems, with absence of the Type IV secretion system.35 These can be classified into two-step and one-step secretion systems. The latter are nanomachines spanning the two bacterial membranes, whereas for the two-step secretion proteins transit through the periplasmic space before they are passing the outer membrane. Secreted proteins are often involved in the hydrolysis of complex structures into digestable nutrients and also supply the cell with essential inorganic ions from the environment. Protein secretion systems play an important role in bacterial virulence. Pathogens use these nanomachines to either release virulence factors into their environment (e.g., elastases LasA and LasB), or direct translocation into the host cell cytosol.36,37 Hence, secretion systems themselves have become validated anti-virulence targets.