title: A Cytolethal Distending Toxin Variant from Aggregatibacter actinomycetemcomitans with an Aberrant CdtB That Lacks the Conserved Catalytic Histidine 160.
abstract: The periodontopathogen Aggregatibacter actinomycetemcomitans synthesizes several virulence factors, including cytolethal distending toxin (CDT). The active CDT holoenzyme is an AB-type tripartite genotoxin that affects eukaryotic cells. Subunits CdtA and CdtC (B-components) allow binding and intracellular translocation of the active CdtB (A-component), which elicits nuclear DNA damage. Different strains of A. actinomycetemcomitans have diverse virulence genotypes, which results in varied pathogenic potential and disease progression. Here, we identified an A. actinomycetemcomitans strain isolated from two patients with advance chronic periodontitis that has a regular cdtABC operon, which, however, codes for a unique, shorter, variant of the CdtB subunit. We describe the characteristics of this CdtBΔ116-188, which lacks the intact nuclear localisation signal and the catalytic histidine 160. We show that the A. actinomycetemcomitans DO15 isolate secretes CdtBΔ116-188, and that this subunit cannot form a holotoxin and is also not genotoxic if expressed ectopically in HeLa cells. Furthermore, the A. actinomycetemcomitans DO15 isolate is not toxic, nor does it induce cellular distention upon infection of co-cultivated HeLa cells. Biological significance of this deletion in the cdtB remains to be explained.
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Davor
authors.initials: D
authors.lastname: Obradović
authors.affiliation: Department of Oral Medicine and Periodontology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Gašperšič
authors.affiliation: Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Simon
authors.initials: S
authors.lastname: Caserman
authors.affiliation: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Adrijana
authors.initials: A
authors.lastname: Leonardi
authors.affiliation: Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Jamnik
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Podlesek
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Seme
authors.affiliation: Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
authors.affiliation: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.|Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Igor
authors.initials: I
authors.lastname: Križaj
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Maček
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Matej
authors.initials: M
authors.lastname: Butala
mesh_terms: D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity; D055113:Chronic Periodontitis / Q000209:etiology / Q000382:microbiology; D017124:Conserved Sequence; D005798:Genes, Bacterial; D014644:Genetic Variation; D006367:HeLa Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D009876:Operon; D011487:Protein Conformation; D017384:Sequence Deletion; D014774:Virulence / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; C067044:cytolethal distending toxin; D006639:Histidine