P 10

The Role of Bacteria-derived Outer-Membrane-Vesicles (OMVs) in the Induction of Systemic Inflammation and Organ Damage

Principal investigators

Univ.-Prof. Dr. rer. nat.

Petra Dersch

Dr. med.

Andreas Margraf


Gram-negative bacterial strains are common causes of both severe community- and hospital-acquired pneumonia and sepsis. The pathophysiological changes that occur during the infection are characterized by the secretion of a myriad of inflammatory mediators, and the recruitment and activation of innate immune cells to eliminate the pathogen. Insufficient combatting of these invading pathogens triggers cell apoptosis, causing tissue damage and loss of barrier function, allowing leakage of the bacteria into the blood circulation. Unhindered dissemination of bacteria frequently induces an overshooting, aggressive immune response which evokes systemic inflammation, organ damage, and ultimately organ failure, such as acute kidney injury or acute respiratory distress syndrome (ARDS). ARDS patients show characteristic features including increased pro-inflammatory cytokine levels, neutrophil infiltration into the lung, increased permeability, and lung edema formation, and worsened pulmonary gas exchange. Over the past years, it became evident, that diffusible outer membrane vesicles (OMVs), released by Gram-negative bacteria during infection, have a very strong impact on host inflammatory responses and intravascular coagulation, and play a critical role in the pathogenesis, dissemination, and disease progression. Nonetheless, mechanisms underlying the contribution of these vesicles to the propagation of inflammatory processes are so far insufficiently understood.

OMVs of Klebsiella pneumoniae strain ART2008133

This project therefore aims to assess the release of OMVs, the impact of OMVs during translational disease models of pulmonary infection, and both the interplay as well as diagnostic potential of OMVs in the setting of inflammation. As a translational approach, we will use adequate disease models and mimic clinically relevant settings, such as in vitro testing of antibiotics to assess the role of OMVs. For this purpose, OMVs will be isolated and characterized from different clinical isolates of gram-negative bacteria, and in vitro immune cell activation assays performed. Further testing of OMVs in in vivo models in combination with the detectability of OMVs in patient samples will aid in understanding the role of OMVs in further detail.

Project Team

Yannick Teschke