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Salmonella typhi Encodes a Functional Cytolethal Distending Toxin That Is Delivered into Host Cells by a Bacterial-Internalization Pathway

Haghjoo, Erik ; Galán, Jorge E. ; Curtiss, Roy

Proceedings of the National Academy of Sciences - PNAS, 2004-03, Vol.101 (13), p.4614-4619 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Salmonella typhi Encodes a Functional Cytolethal Distending Toxin That Is Delivered into Host Cells by a Bacterial-Internalization Pathway
Autor: Haghjoo, Erik ; Galán, Jorge E. ; Curtiss, Roy
Assuntos: Animals ; Bacteria ; Bacterial Toxins - pharmacokinetics ; Biological Sciences ; Biological Transport ; Cell Cycle ; Cell Line ; Cells, Cultured ; Chloramphenicol - pharmacology ; Cultured cells ; Epithelial cells ; Genes, Reporter ; Infections ; Internalization ; Intestinal Mucosa - microbiology ; Intestinal Mucosa - pathology ; Intoxication ; Luciferases - analysis ; Microbiology ; Pathogens ; Protein Synthesis Inhibitors - pharmacology ; Salmonella enterica ; Salmonella typhi ; Salmonella typhi - drug effects ; Salmonella typhi - growth & development ; Salmonella typhi - pathogenicity ; Toxicity ; Toxins ; Typhoid
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2004-03, Vol.101 (13), p.4614-4619
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Abbreviations: CDT, cytolethal distending toxin; S. typhi, Salmonella enterica serovar Typhi; TTSS, type III secretion system; DAP, diaminopimelic acid; ER, endoplasmic reticulum.
To whom correspondence should be addressed. E-mail: jorge.galan@yale.edu.
Communicated by Roy Curtiss, Washington University, St. Louis, MO, February 9, 2004
Descrição: Many bacterial pathogens encode the cytolethal distending toxin (CDT), which causes host cells to arrest during their cell cycle by inflicting DNA damage. CDT is composed of three proteins, CdtA, CdtB, and CdtC. CdtB is the enzymatically active or A subunit, which possesses DNase I-like activity, whereas CdtA and CdtC function as heteromeric B subunits that mediate the delivery of CdtB into host cells. We show here that Salmonella enterica serovar Typhi encodes CDT activity, which depends on the function of a CdtB homologous protein. Remarkably, S. enterica serovar Typhi does not encode apparent homologs of CdtA or CdtC. Instead, we found that toxicity, as well as cdtB expression, requires bacterial internalization into host cells. We propose a pathway of toxin delivery in which bacterial internalization relieves the requirement for the functional equivalent of the B subunit of the CDT toxin.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Salmonella typhi Encodes a Functional Cytolethal Distending Toxin That Is Delivered into Host Cells by a Bacterial-Internalization Pathway

Haghjoo, Erik ; Galán, Jorge E. ; Curtiss, Roy

United States: National Academy of Sciences

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