Abstract
Salmonella Typhimurium definitive phage type (DT) 104 produces a pertussis-like toxin (ArtAB-DT104), which catalyzes ADP-ribosylation of pertussis toxin sensitive G proteins. However, the prevalence of ArtAB and its toxicity have not been established. We report here that, in addition to DT104, S. Worthington, and S. bongori, produce ArtAB homologs, designated ArtAB-SW and ArtAB-Sb, respectively. We purified and characterized these ArtAB toxins, which comprise a 27-kDa A subunit (ArtA) and 13.8-kDa pentameric B subunits (ArtB). While the sequence of the A subunit, which is ADP-ribosyltransferase, is similar to the A subunit sequences of other ArtABs, the B subunit of ArtAB-Sb is divergent compared to the B subunit sequences of other ArtABs. Intraperitoneal injection of purified ArtABs was fatal in mice; the 50% lethal doses of ArtAB-DT104 and ArtAB-SW were lower than that of ArtAB-Sb, suggesting that ArtB plays an influential role in the toxicity of ArtABs. ArtABs catalyzed ADP-ribosylation of G proteins in RAW 264.7 murine macrophage-like cells, and increased intracellular cyclic AMP levels. ArtAB-DT104 and ArtAB-SW, but not ArtAB-Sb, stimulated insulin secretion in mice; however, unlike Ptx, ArtABs did not induce leukocytosis. This disparity in biological activity may be explained by differences in ADP-ribosylation of target G proteins.
Highlights
Salmonella spp. cause infectious diseases, such as gastroenteritis, which is associated with diarrhea and inflammatory responses
We examined the prevalence of Salmonella pertussis-like toxins (ArtABs), and found that artAB was present in 97.5% (237/243) of Salmonella Typhimurium DT104 isolates, but only 3.6% (11/303) of non-DT104 isolates
Typhimurium DT104, and a number of other toxin genes are encoded by phages; such genes are typically replicated and transcriptionally activated after prophage induction[17, 18]
Summary
Salmonella spp. cause infectious diseases, such as gastroenteritis, which is associated with diarrhea and inflammatory responses. Typhimurium DT104 genome, we recently identified two genes, artA and artB (artAB), encoding polypeptides with amino acid (a.a.) sequence similarity to the pertussis toxin (Ptx), ADP-ribosyltransferase A subunit (S1 unit), and one of five components of the heteropentameric B subunits (S2 unit)[8]. ADP-ribosyltransferase toxins are broadly distributed among highly pathogenic bacteria, and are the primary cause of severe human diseases, such as diphtheria, cholera, and pertussis. All of these toxins belong to the AB subunit class, where the A subunit is the toxic moiety that harbors the active site, and the B subunit is required for receptor binding and the translocation of fragment A across the host cell membrane[10, 11]. We describe the purification of ArtAB toxins from these organisms and the characterization of their biological and physicochemical properties
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