In the Absence of Effector Proteins, the Pseudomonas aeruginosa Type Three Secretion System Needle Tip Complex Contributes to Lung Injury and Systemic Inflammatory Responses

• DOI: 10.1371/journal.pone.0081792
• Publication Date: 2013-11-27T23:47:42Z
• Authors: Jonathon P. Audia; Ashley S. Lindsey; Nicole A. Housley; Courtney R. Ochoa; Chun Zhou; Michie Toba; Masahiko Oka; Naga S. Annamdevula; Meshann S. Fitzge...; Dara W. Frank; Diego F. Alvarez
• Keywords: Male; 0303 health sciences; Time Factors; Cell Death; Science; Q; R; Endothelial Cells; Systemic Inflammatory Response Syndrome; Rats; 3. Good health; 03 medical and health sciences; Microvessels; Pseudomonas aeruginosa; Medicine; Animals; Pseudomonas Infections; Bacterial Secretion Systems; Lung; Research Article

Herein we describe a pathogenic role for the Pseudomonas aeruginosa type three secretion system (T3SS) needle tip complex protein, PcrV, in causing lung endothelial injury. We first established model which P. wild strain PA103 caused pneumonia-induced sepsis and distal organ dysfunction. Interestingly, derivative lacking its two known secreted effectors, ExoU ExoT [denoted (ΔU/ΔT)], also modest injury whereas an isogenic T3SS assembly protein (ΔPcrV)] did not. (ΔU/ΔT) infection neutrophil influx into parenchyma, injury, (reminiscent of sepsis). In contrast, (ΔPcrV) nominal infiltration but no further examined mechanisms using cultured rat pulmonary microvascular cells (PMVECs) revealed two-phase, temporal nature infection. At 5-hours post-inoculation (early phase infection), elicited PMVEC barrier disruption via perturbation actin cytoskeleton so cell death-independent manner. Conversely, not elicit early disruption. 24-hours (late induced damage death that displayed apoptotic component. Although late death, it to attenuated extent. The mutants grew at similar rates were able adhere equally PMVECs indicating observed differences are likely attributable complex-mediated post host attachment. Together, these data suggest and/or another undefined effector(s) important determinants