Journal Article

PUBDB-2025-02288

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Unveiling the structure, function and dynamics of StmPr1 in Stenotrophomonas maltophilia virulence

Sommer, M. (Corresponding author)Extern* ; Negm, A. ; Outzen, L. ; Windhorst, S. ; Gabdulkhakov, A. ; Weber, W. ; Betzel, C. (Corresponding author)Extern*

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-025-06177-5  doi:10.3204/PUBDB-2025-02288

Abstract: The increase in infections caused by multi-resistant Gram-negative bacteria, like Stenotrophomonas maltophilia, has become a growing health crisis worldwide. S. maltophilia poses a risk because of its tendency to opportunistically infecting patience for example through colonization of catheters in hospital environments using its intrinsic resistance against multiple antibiotics. Through the COVID-19 pandemic it gained more prominence by being a key pathogen in respiratory co-infections. This study will present a structural analysis of StmPr1, S. maltophilia’s main virulence factor, an excreted serine protease. Our study outline structure and functional aspects of StmPr1, revealing a unique autoproteolytic activity resulting in a shortened version of the active enzyme. We also investigated the potential of two groups of peptide-based inhibitors, one being acetyl- and the other being boron-based inhibitors. The focus here lies on Bortezomib, a boron-based serine protease inhibitor, and its potential therapeutic use against S. maltophilia. We provide a structure-function analysis which includes X-ray crystallography data with resolutions ranging from 1.64 to 2.08 Å, molecular dynamic simulations and small-angle X-ray scattering (SAXS) experiments. These data provide a deeper understanding of StmPr1’s resilience and mechanisms, while highlighting the relevance of StmPr1’s C-terminal extension for correct folding and its stability. Moreover, it also shows that StmPr1 is promising target for further drug discovery investigations to identify compounds and drugs to treat S. maltophilia infections.

Note: 05K20GUB

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. AIM, DFG project G:(GEPRIS)390715994 - EXC 2056: CUI: Advanced Imaging of Matter (390715994) (390715994)
3. 05K19GU4 - SFX2: Hochdurchsatz Serielle-Femtosekunden Kristallographie @ EU XFEL. (BMBF-05K19GU4) (BMBF-05K19GU4)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)
2. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2025

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