Role of sphingomyelinase in infectious diseases caused by Bacillus cereus

• Published in: PloS one 2012-06, Vol.7 (6), p.e38054
• Main Authors: Oda, Masataka, Hashimoto, Manabu, Takahashi, Masaya, Ohmae, Yuka, Seike, Soshi, Kato, Ryoko, Fujita, Aoi, Tsuge, Hideaki, Nagahama, Masahiro, Ochi, Sadayuki, Sasahara, Teppei, Hayashi, Shunji, Hirai, Yoshikazu, Sakurai, Jun
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Bacterial - immunology; Antibodies, Bacterial - pharmacology; Bacillus cereus; Bacillus cereus - enzymology; Bacillus cereus - growth & development; Bacillus cereus - immunology; Base Sequence; Biology; Ceramide; Chromatography, Thin Layer; Clinical isolates; Clostridium perfringens; Communicable diseases; Confocal; Enzymatic activity; Enzymes; Fluidity; Genotype & phenotype; Health aspects; Helicobacter pylori; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Immunization; Infection; Infectious diseases; Laser microscopy; Lipids; Listeria; Macrophages; Macrophages - immunology; Macrophages - metabolism; Medical research; Medical treatment; Medicine; Membrane fluidity; Membranes; Metabolism; Mice; Microorganisms; Microscopy; Microscopy, Confocal; Molecular Sequence Data; Mortality; Nosocomial infections; Opportunist infection; Pathogens; Patients; Peptidoglycans; Phagocytosis; Phagocytosis - drug effects; Pharmaceutical sciences; Photobleaching; Promoter Regions, Genetic - genetics; Recombinant Proteins - genetics; Reduction; Sepsis; Sepsis - microbiology; Septicemia; Sequence Analysis, DNA; Sheep; Soil Microbiology; Sphingomyelin phosphodiesterase; Sphingomyelin Phosphodiesterase - genetics; Sphingomyelin Phosphodiesterase - immunology; Sphingomyelin Phosphodiesterase - metabolism; Staphylococcus aureus; Staphylococcus infections; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Virulence; Virulence factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038054

Bacillus cereus (B. cereus) is a pathogen in opportunistic infections. Here we show that Bacillus cereus sphingomyelinase (Bc-SMase) is a virulence factor for septicemia. Clinical isolates produced large amounts of Bc-SMase, grew in vivo, and caused death among mice, but ATCC strains isolated from soil did not. A transformant of the ATCC strain carrying a recombinant plasmid containing the Bc-SMase gene grew in vivo, but that with the gene for E53A, which has little enzymatic activity, did not. Administration of an anti-Bc-SMase antibody and immunization against Bc-SMase prevented death caused by the clinical isolates, showing that Bc-SMase plays an important role in the diseases caused by B. cereus. Treatment of mouse macrophages with Bc-SMase resulted in a reduction in the generation of H(2)O(2) and phagocytosis of macrophages induced by peptidoglycan (PGN), but no effect on the release of TNF-α and little release of LDH under our experimental conditions. Confocal laser microscopy showed that the treatment of mouse macrophages with Bc-SMase resulted in the formation of ceramide-rich domains. A photobleaching analysis suggested that the cells treated with Bc-SMase exhibited a reduction in membrane fluidity. The results suggest that Bc-SMase is essential for the hydrolysis of SM in membranes, leading to a reduction in phagocytosis.