title: Transcriptional Profile during Deoxycholate-Induced Sporulation in a Clostridium perfringens Isolate Causing Foodborne Illness.
abstract: Clostridium perfringens type A is a common source of foodborne illness (FBI) in humans. Vegetative cells sporulate in the small intestinal tract and produce the major pathogenic factor C. perfringens enterotoxin. Although sporulation plays a critical role in the pathogenesis of FBI, the mechanisms inducing sporulation remain unclear. Bile salts were shown previously to induce sporulation, and we confirmed deoxycholate (DCA)-induced sporulation in C. perfringens strain NCTC8239 cocultured with human intestinal epithelial Caco-2 cells. In the present study, we performed transcriptome analyses of strain NCTC8239 in order to elucidate the mechanism underlying DCA-induced sporulation. Of the 2,761 genes analyzed, 333 were up- or downregulated during DCA-induced sporulation and included genes for cell division, nutrient metabolism, signal transduction, and defense mechanisms. In contrast, the virulence-associated transcriptional regulators (the VirR/VirS system, the agr system, codY, and abrB) were not activated by DCA. DCA markedly increased the expression of signaling molecules controlled by Spo0A, the master regulator of the sporulation process, whereas the expression of spo0A itself was not altered in the presence or absence of DCA. The phosphorylation of Spo0A was enhanced in the presence of DCA. Collectively, these results demonstrated that DCA induced sporulation, at least partially, by facilitating the phosphorylation of Spo0A and activating Spo0A-regulated genes in strain NCTC8239 while altering the expression of various genes.
  
  
  
  Disease caused by Clostridium perfringens type A consistently ranks among the most common bacterial foodborne illnesses in humans in developed countries. The sporulation of C. perfringens in the small intestinal tract is a key event for its pathogenesis, but the factors and underlying mechanisms by which C. perfringens sporulates in vivo currently remain unclear. Bile salts, major components of bile, which is secreted from the liver for the emulsification of lipids, were shown to induce sporulation. However, the mechanisms underlying bile salt-induced sporulation have not yet been clarified. In the present study, we demonstrate that deoxycholate (one of the bile salts) induces sporulation by facilitating the phosphorylation of Spo0A and activating Spo0A-regulated genes using a transcriptome analysis. Thus, this study enhances our understanding of the mechanisms underlying sporulation, particularly that of bile salt-induced sporulation, in C. perfringens.
authors.affiliation: Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan shishimaru@vet.osakafu-u.ac.jp.
authors.forename: Mayo
authors.initials: M
authors.lastname: Yasugi
authors.affiliation: DNA Chip Development Center, RIMD, Osaka University, Suita, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Kuwana
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takamatsu
authors.affiliation: Biology and Biochemistry Department, University of Houston, Houston, Texas, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Department of Biomedical Sciences, Oregon State University, Corvallis, Oregon, USA.|Department of Microbiology, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Mahfuzur R
authors.initials: MR
authors.lastname: Sarker
authors.affiliation: Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Miyake
mesh_terms: D003015:Clostridium Infections / Q000382:microbiology; D003016:Clostridium perfringens / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D003840:Deoxycholic Acid / Q000378:metabolism*; D005517:Foodborne Diseases / Q000382:microbiology; D020869:Gene Expression Profiling; D006801:Humans; D013171:Spores, Bacterial / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*
chemical_list: D003840:Deoxycholic Acid