Pyruvate oxidase of Streptococcus pneumoniae contributes to pneumolysin release

Abstract

Background Streptococcus pneumoniae is one of the leading causes of community acquired pneumonia and acute otitis media. Certain aspects of S. pneumoniae’s virulence are dependent upon expression and release of the protein toxin pneumolysin (PLY) and upon the activity of the peroxide-producing enzyme, pyruvate oxidase (SpxB). We investigated the possible synergy of these two proteins and identified that release of PLY is enhanced by expression of SpxB prior to stationary phase growth.ResultsMutants lacking the spxB gene were defective in PLY release and complementation of spxB restored PLY release. This was demonstrated by cytotoxic effects of sterile filtered supernatants upon epithelial cells and red blood cells. Additionally, peroxide production appeared to contribute to the mechanism of PLY release since a significant correlation was found between peroxide production and PLY release among a panel of clinical isolates. Exogenous addition of H2O2 failed to induce PLY release and catalase supplementation prevented PLY release in some strains, indicating peroxide may exert its effect intracellularly or in a strain-dependent manner. SpxB expression did not trigger bacterial cell death or LytA-dependent autolysis, but did predispose cells to deoxycholate lysis.ConclusionsHere we demonstrate a novel link between spxB expression and PLY release. These findings link liberation of PLY toxin to oxygen availability and pneumococcal metabolism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0881-6) contains supplementary material, which is available to authorized users.

Cell Invasion and Pyruvate Oxidase-Derived H 2 O 2 Are Critical for Streptococcus pneumoniae-Mediated Cardiomyocyte Killing

“…Ongoing studies in the laboratory are exploring this possibility. Recent studies by Bryant et al also suggest that H 2 O 2 can potentiate the effect of pneumolysin by increasing its activity or release from S. pneumoniae (35). These possibilities are favored by our result showing that deletion of SpxB or pneumolysin dramatically reduced HL-1 cell death in a manner that was synergetic and not additive.…”

Mucosal Infections and Invasive Potential of Nonencapsulated Streptococcus pneumoniae Are Enhanced by Oligopeptide Binding Proteins AliC and AliD

“…Interestingly, proteins associated with virulence in encapsulated bacteria, such as the PspC variant (CbpAC, NCBI accession no. EPD17685.1 ), NADH oxidase ( EPD21629.1 ), and pyruvate oxidase ( EPD21778.1 ), were upregulated in strain MNZ41 compared to strain JLB01 ( 31 , 36 – 38 ). However, what occurs between substrate import and phenotype modification through protein dysregulation remains unknown.…”

Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis

“…Consequently pneumolysin-exposed cells undergo cell cycle arrest and apoptosis, although the induction of NKG2D-Ls was not investigated in this study ( 91 ). Interestingly, pyruvate oxidase, another cytotoxin released by S. pneumoniae , induces DSBs and contributes to pneumolysin release ( 81 ).…”