Journal Article

Concerted Action of Sphingomyelinase and Non-Hemolytic Enterotoxin in Pathogenic Bacillus cereus

Vogelmann, Roger, Doll, Viktoria M., Ehling-Schulz, Monika

2013

Overview

Bacillus cereus causes food poisoning and serious non-gastrointestinal-tract infections. Non-hemolytic enterotoxin (Nhe), which is present in most B. cereus strains, is considered to be one of the main virulence factors. However, a B. cereus ΔnheBC mutant strain lacking Nhe is still cytotoxic to intestinal epithelial cells. In a screen for additional cytotoxic factors using an in vitro model for polarized colon epithelial cells we identified B. cereus sphingomyelinase (SMase) as a strong inducer of epithelial cell death. Using single and double deletion mutants of sph, the gene encoding for SMase, and nheBC in B. cereus we demonstrated that SMase is an important factor for B. cereus cytotoxicity in vitro and pathogenicity in vivo. SMase substantially complemented Nhe induced cytotoxicity in vitro. In addition, SMase but not Nhe contributed significantly to the mortality rate of larvae in vivo in the insect model Galleria mellonella. Our study suggests that the role of B. cereus SMase as a secreted virulence factor for in vivo pathogenesis has been underestimated and that Nhe and SMase complement each other significantly to cause full B. cereus virulence hence disease formation.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Bacillus cereus / Bacillus cereus - enzymology / Bacillus cereus - metabolism / Bacillus cereus - pathogenicity / Binding sites / Biocompatibility / Biology / Cell death / Clonal deletion / Clostridium perfringens / Colon / Cytotoxic factors / Cytotoxicity / Deletion mutant / Enterotoxins - genetics / Enterotoxins - metabolism / Enzymes / Epithelial cells / Food / Food contamination / Food poisoning / Galleria mellonella / Gastrointestinal tract / Gene deletion / Genes / Health aspects / In vivo methods and tests / Infection / Insecta - microbiology / Insects / Intestine / Larvae / Lymphocytes B / Medicine / Multivariate analysis / Mutants / Pathogenesis / Pathogenicity / Pathogens / Plasmids / Rodents / Sphingomyelin phosphodiesterase / Sphingomyelin Phosphodiesterase - genetics / Sphingomyelin Phosphodiesterase - metabolism / Staphylococcus aureus / Toxicity / Virulence / Virulence (Microbiology) / Virulence factors / Virulence Factors - genetics / Virulence Factors - metabolism