Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumonia

ABSTRACT: Bacterial lytic polysaccharide monooxygenases (LPMOs) are understudied in the context of infection disease. We demonstrated that Pseudomonas aeruginosa LPMO CbpD is a virulence determinant in pneumonia. Moreover, Mice immunized with CbpD generate robust antibody responses that provide protection against lethal lung infection

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Jack-Ansgar Bruun

LAB HEAD: Victor Nizet

PROVIDER: PXD039298 | Pride | 2023-07-26

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against <i>Pseudomonas aeruginosa</i> pneumonia.

Askarian Fatemeh F Tsai Chih-Ming CM Cordara Gabriele G Zurich Raymond H RH Bjånes Elisabet E Golten Ole O Vinther Sørensen Henrik H Kousha Armin A Meier Angela A Chikwati Elvis E Bruun Jack-Ansgar JA Ludviksen Judith Anita JA Choudhury Biswa B Trieu Desmond D Davis Stanley S Edvardsen Per Kristian Thorén PKT Mollnes Tom Eirik TE Liu George Y GY Krengel Ute U Conrad Douglas J DJ Vaaje-Kolstad Gustav G Nizet Victor V

Proceedings of the National Academy of Sciences of the United States of America 20230717 30

<i>Pseudomonas aeruginosa</i> (PA) CbpD belongs to the lytic polysaccharide monooxygenases (LPMOs), a family of enzymes that cleave chitin or related polysaccharides. Here, we demonstrate a virulence role of CbpD in PA pneumonia linked to impairment of host complement function and opsonophagocytic clearance. Following intratracheal challenge, a PA ΔCbpD mutant was more easily cleared and produced less mortality than the wild-type parent strain. The x-ray crystal structure of the CbpD LPMO domain ...[more]

PMID: 37459522

Similar Datasets

PTMs of the lytic polysaccharide monooxygenase of Pseudomonas aeruginosa

2021-01-12 | PXD018769 | Pride

The lytic polysaccharide monooxygenase of Pseudomonas aeruginosa promotes bacterial survival during systemic infection

Project description:Lytic polysaccharide monooxygenases (LPMOs) are a recently discovered enzyme family that cleave polysaccharides by oxidation. Despite proposed roles in bacterial virulence, no direct functional data exist to validate these claims. Here we show that CpbD, the LPMO of the opportunistic pathogen Pseudomonas aeruginosa (PA) is a virulence factor that promotes survival of the bacterium in whole human blood. CbpD was also shown to cleave the glycosidic bonds of the model substrate by an oxidative reaction, a feature that promoted by azurin and pyocyanin. Two redox-active virulence factors co-secreted with the LPMO. Combination of homology modelling, molecular dynamics simulations and small angle X-ray scattering demonstrated that CbpD is a monomeric tri-modular enzyme with highly flexible domain linkers, where domain positioning may be influenced by post translational modifications. Deletion of cbpD rendered P. aeruginosa unable to establish a lethal systemic infection and enhanced bacterial clearance in vivo. Improved bacterial survival of the wildtype was not attributable to dampening of pro-inflammatory responses by the protein, either ex vivo or in vivo. Further quantification of complement products in whole human blood revealed that CbpD reduced the performance of the terminal complement cascade. Importantly, CbpD inactivation by active site mutations abolished both enzyme activity in vitro and function ex vivo, indicating that ligand oxidation is crucial for CbpD virulence function. Finally, profiling of the bacterial and splenic proteome showed that the lack of this single enzyme resulted in substantial re-organization of the bacterial defense systems in vitro and the targeting of distinct host proteins/pathways in vivo.

2021-01-28 | PXD021888 | Pride

The lytic polysaccharide monooxygenase of Pseudomonas aeruginosa promotes bacterial survival during systemic infection

2021-01-28 | PXD017971 | Pride

A seven-transmembrane methyltransferase catalysing N-terminal histidine methylation of lytic polysaccharide monooxygenases

Project description:Lytic polysaccharide monooxygenases (LPMOs) are oxidative enzymes that help break down lignocellulose, making them highly attractive for improving biomass utilization in biotechnological purposes. The catalytically essential N-terminal histidine (His1) of LPMOs is post-translationally modified by methylation in filamentous fungi to protect them from auto-oxidative inactivation, however, the responsible methyltransferase enzyme is unknown. Using mass-spectrometry-based quantitative proteomics in combination with systematic CRISPR/Cas9 knockout screening in Aspergillus nidulans, we identified the N-terminal histidine methyltransferase (NHMT) encoded by the gene AN4663. Targeted proteomics confirmed that NHMT was solely responsible for His1 methylation of LPMOs. NHMT is predicted to encode a unique seven-transmembrane segment anchoring a soluble methyltransferase domain. Co-localization studies showed endoplasmic reticulum residence of NHMT and co-expression in the industrial production yeast Komagataella phaffii with LPMOs resulted in His1 methylation of the LPMOs. This demonstrates the biotechnological potential of recombinant production of proteins and peptides harbouring this unique post-translational modification.

2023-07-14 | PXD037734 | Pride

Chitinolytic enzymes confer pathogenicity of Aliivibrio salmonicida LFI1238 in the invasive phase of cold-water vibriosis

Project description:Aliivibrio (Vibrio) salmonicida is the causative agent of cold-water vibriosis in salmonids (Oncorhynchus mykiss and Salmo salar L.) and gadidae (Gadus morhua L.). Virulence-associated factors that are essential for the full spectrum of Al. salmonicida pathogenicity are largely unknown. Chitin-active lytic polysaccharide monooxygenases (LPMOs) have been indicated to play roles in both chitin degradation and virulence in a variety of pathogenic bacteria. In the present study we investigated the role of LPMOs in the pathogenicity of Al. salmonicida LFI238 in Atlantic salmon (Salmo salar L.). In vivo challenge experiments using isogenic deletion mutants of the two LPMOs encoding genes AsLPMO10A and AsLPMO10B, showed that both LPMOs, and in particular AsLPMO10B, were important in the invasive phase of cold-water vibriosis. Crystallographic analysis of the AsLPMO10B AA10 LPMO domain (to 1.4 Å resolution) revealed high structural similarity to viral fusolin, an LPMO known to enhance the virulence of insecticidal agents. Finally, exposure to Atlantic salmon serum resulted in substantial proteome re-organization of the Al. salmonicida LPMO deletion variants compared to the wild type strain, indicating the struggle of the bacterium to adapt to the host immune components.

2022-10-13 | PXD031437 | Pride