The Pseudomonas aeruginosa type III secretion system has an exotoxin S/T/Y independent pathogenic role during acute lung infection

The type III secretion system (T3SS) is a complex nanomachine of many pathogenic Gram-negative bacteria. It forms a proteinaceous channel that is inserted into the host eukaryotic cell membrane for injection of bacterial proteins that manipulate host cell signaling. However, few studies have focused on the effector-independent functions of the T3SS. Using a murine model of acute lung infection with Pseudomonas aeruginosa, an important human opportunistic pathogen, we compared the pathogenicity of mutant bacteria that lack all of the known effector toxins (Delta STY), with mutant bacteria that also lack the major translocator protein PopB (Delta STY/Delta PopB) and so cannot form a functional T3SS channel in the host cell membrane. Mortality was higher among mice challenged with Delta STY compared to mice challenged with Delta STY/Delta PopB mutant bacteria. In addition, mice infected with Delta STY showed decreased bacterial clearance from the lungs compared to those infected with Delta STY/Delta PopB. Infection was in both cases associated with substantial killing of lung infiltrating macrophages. However, macrophages from Delta STY-infected mice died by pro-inflammatory necrosis characterized by membrane permeabilization and caspase-1 mediated IL-1 beta production, whereas macrophages from Delta STY/Delta PopB infected mice died by apoptosis, which is characterized by annexin V positive staining of the cell membrane and caspase-3 activation. This was confirmed in macrophages infected in vitro. These results demonstrate a T3SS effector toxin independent role for the T3SS, in particular the T3SS translocator protein PopB, in the pathogenicity of P. aeruginosa during acute lung infection.

Publication year:2012