Helicobacter pylori gamma-glutamyltransferase relates to proteomic adaptations important for colonization

ABSTRACT: Helicobacter pylori γ-glutamyltransferase (gGT) is a conserved virulence factor promoting bacterial colonization and immune tolerance. Although some studies addressed potential mechanisms explaining its function, the supportive role of gGT for in-vivo colonization remains unclear. In addition, it is unknown how differences in gGT expression observed for different strains may lead to compensatory mechanisms to ensure infection and persistence. Hence, it is of high importance to understand more profoundly the in-vivo function of this enzyme. In this study, we assessed acid survival under physiologic conditions mimicking the human gastric fluid and elevated the pH in the murine stomach prior to H. pylori infection to link gGT-mediated acid resistance to colonization. Furthermore, by comparing protein expression levels between wildtype and gGT-deficient H. pylori isolates before and after infecting mice, we systematically investigated proteomic adaptations of gGT-deficient bacteria during infection. Our data indicate that gGT plays a crucial role in sustaining urease activity in acidic environments, thereby supporting bacterial survival and successful colonization. The absence of gGT triggers the expression of proteins involved in nitrogen and iron metabolism, indicating a potential functional role of gGT in these metabolic pathways. Moreover, we observed an impaired growth of gGT-deficient strains in iron-restricted medium. In addition, the absence of gGT during infection leads to a significant overexpression of H. pylori adhesins and flagellar proteins, resulting in increased motility and adhesion capacity. In summary, we identified gGT-dependent mechanisms conferring a growth advantage to the bacterium in the gastric environment, which renders gGT a valuable target for the development of new treatments against H. pylori infection.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Helicobacter Pylori G27 Helicobacter Pylori Pmss1

TISSUE(S): Stomach

SUBMITTER: Nina Bach  

LAB HEAD: Stephan Axel Sieber

PROVIDER: PXD050334 | Pride | 2025-04-08

REPOSITORIES: Pride