Cytotoxic mechanism of cytolethal distending toxin in nontyphoidal Salmonella serovar (Salmonella Javiana) during macrophage infection.
Cytolethal distending toxin B (cdtB) is a conserved virulence factor in Salmonella enterica serovar Typhi. Here we report the presence and functionality of cdtB in some nontyphoidal Salmonella (NTS) serovars, including Salmonella Javiana (cdtB+wt S. Javiana), isolated from imported food. To understand the role of cdtB in NTS serovars, a deletion mutant (cdtB(-)ΔS. Javiana) was constructed. Macrophages were infected with cdtB+wt S. Javiana (wild type), cdtB(-)Δ S. Javiana (mutant), and cdtB-negative NTS serovar (S. Typhimurium). Cytotoxic activity and transcription level of genes involved in cell death (apoptosis, autophagy, and necrosis) were assessed in infected macrophages. The cdtB+wt S. Javiana caused cellular distension as well as high degree of vacuolization and presence of the autophagosome marker LC3 in infected macrophages as compared with cdtB(-)ΔS. Javiana. The mRNA expression of genes involved in the induction of autophagy in response to toxin (Esr1 and Pik3C3) and coregulators of autophagy and apoptosis (Bax and Cyld) were significantly upregulated in cdtB(+)wt S. Javiana-infected macrophages. As autophagy destroys internalized pathogens in addition to the infected cell, it may reduce the spread of infection.
Division of Microbiology, National Center for Toxicological Research , U.S. Food and Drug Administration, Jefferson, Arkansas.
Katherine
K
Williams
Kuppan
K
Gokulan
Diamond
D
Shelman
Tatsuya
T
Akiyama
Ashraf
A
Khan
Sangeeta
S
Khare
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics*; D002460:Cell Line; D048430:Cell Shape / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD; D047628:Estrogen Receptor alpha / Q000235:genetics; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D009336:Necrosis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012475:Salmonella / Q000145:classification / Q000235:genetics* / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics
D001427:Bacterial Toxins; D003546:Cysteine Endopeptidases; D000074749:Deubiquitinating Enzyme CYLD; D047628:Estrogen Receptor alpha; D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D051028:bcl-2-Associated X Protein; C480860:Map1lc3b protein, mouse; C067044:cytolethal distending toxin; C511601:CYLD protein, mouse