The function of the HtrA protease in maintaining homeostasis of the human pathogen Helicobacter pylori

Helicobacter pylori is a Gram-negative bacterium known to cause persistent infections in humans. HtrA protease is one of the most important secreted virulence factors of this pathogen and is responsible for damaging intercellular junctions between the gastric epithelial cells. Although this protein is regarded as essential in H. pylori, very little is known about its function in the bacterial cell physiology. In this work, we attempted to expand the knowledge in this aspect. We found that deletion of the htrA gene caused significant alterations in the membrane proteome, including changes in the content of many outer membrane proteins. This translated into modifications in the cell surface properties, affecting the function of the outer membrane as a barrier in the mutant cells. Interestingly, maintaining the homeostasis of cellular envelope was dependent mainly on the chaperone activity; the role of proteolytic activity was far less important in this respect, considering the proteomic data and the surface properties of the bacteria. In vitro, HtrA degraded several H. pylori proteins, including proteins involved in virulence: oncogenic effector CagA, whose degradation products accumulated in H. pylori ΔhtrA cells, and the iron-regulated OM protein FrpB4. In conclusion, the results presented in this work underline the very important role of the HtrA protein in the maintenance of the cellular envelope proteostasis in H. pylori. Disrupted homeostasis in the absence of HtrA function can significantly impair the physiology of the whole H. pylori cell, which may affect its virulent properties.