In bacteria, the DsbA oxidoreductase is a crucial factor responsible for the introduction of disulfide bonds to extracytoplasmic proteins, which include important virulence factors. A lack of proper disulfide bonds frequently leads to instability and/or loss of protein function; therefore, improper disulfide bonding may lead to avirulent phenotypes. The importance of the DsbA function in phytopathogens has not been extensively studied yet. is a bacterium from the Soft Rot family which is responsible for very high economic losses mainly in potato. In this work, we constructed a mutant and demonstrated that a lack of DsbA caused a loss of virulence. The mutant bacteria showed lower activities of secreted virulence determinants and were unable to develop disease symptoms in a potato plant. The SWATH-MS-based proteomic analysis revealed that the mutation led to multifaceted effects in the cells, including not only lower levels of secreted virulence factors, but also the induction of stress responses. Finally, the outer membrane barrier seemed to be disturbed by the mutation. Our results clearly demonstrate that the function played by the DsbA oxidoreductase is crucial for virulence, and a lack of DsbA significantly disturbs cellular physiology.
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http://dx.doi.org/10.3390/ijms23020697 | DOI Listing |
PLoS Genet
December 2024
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
The Rcs (regulator of capsule synthesis) phosphorelay is a conserved cell envelope stress response mechanism in enterobacteria. It responds to perturbations at the cell surface and the peptidoglycan layer from a variety of sources, including antimicrobial peptides, beta-lactams, and changes in osmolarity. RcsF, an outer membrane lipoprotein, is the sensor for this pathway and activates the phosphorelay by interacting with an inner membrane protein IgaA.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, Australia.
In bacteria the formation of disulphide bonds is facilitated by a family of enzymes known as the disulphide bond forming (Dsb) proteins, which, despite low sequence homology, belong to the thioredoxin (TRX) superfamily. Among these enzymes is the disulphide bond-forming protein A (DsbA); a periplasmic thiol oxidase responsible for catalysing the oxidative folding of numerous cell envelope and secreted proteins. Pathogenic bacteria often contain diverse Dsb proteins with distinct functionalities commonly associated with pathogenesis.
View Article and Find Full Text PDFMol Med
November 2024
Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Background: Pulmonary fibrosis (PF) is a progressive and difficult-to-heal lung disease that poses a significant threat to human life and health. This study aimed to investigate the potential pathological mechanisms of PF and to identify new avenues for the treatment of PF.
Methods: Clinical samples were collected to assess the effect of disulfide-bond A oxidoreductase-like protein (DsbA-L) on PF.
bioRxiv
September 2024
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD., 20892.
J Biol Chem
June 2024
Department of Biology, Indiana University, Bloomington, Indiana, USA. Electronic address:
Disulfide bond formation has a central role in protein folding of both eukaryotes and prokaryotes. In bacteria, disulfide bonds are catalyzed by DsbA and DsbB/VKOR enzymes. First, DsbA, a periplasmic disulfide oxidoreductase, introduces disulfide bonds into substrate proteins.
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