Characterization of pertussis-like toxin from Salmonella spp. that catalyzes ADP-ribosylation of G proteins

Tamamura, Yukino; Tanaka, Kiyoshi; Uchida, Ikuo

doi:10.1038/s41598-017-02517-2

Cited by 28 publications

(75 citation statements)

References 38 publications

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“…Recently, the genes artA and artB (artAB) were identified within the prophage of S. Typhimurim DT104 (8). These genes encode polypeptides with amino acid 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][9][10]. Additionally, the serotypes S. Worthington and S. Agoueve and the species S. bongori were shown to harbour artAB homologues [10].…”

Section: Introductionmentioning

confidence: 99%

“…These genes encode polypeptides with amino acid 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][9][10]. Additionally, the serotypes S. Worthington and S. Agoueve and the species S. bongori were shown to harbour artAB homologues [10]. While the A subunit shows sequence similarity with other ArtABs, the B subunit sequence of S. bongori ArtAB (ArtAB-Sb) is divergent [10].…”

Section: Introductionmentioning

confidence: 99%

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Influence of SOS-inducing agents on the expression of ArtAB toxin gene in Salmonella enterica and Salmonella bongori

et al. 2020

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Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) definitive phage type 104 (DT104), S. enterica subspecies enterica serovar Worthington (S. Worthington) and S. bongori produce ArtA and ArtB (ArtAB) toxin homologues, which catalyse ADP-ribosylation of pertussis toxin-sensitive G protein. ArtAB gene (artAB) is encoded on prophage in DT104 and its expression is induced by mitomycin C (MTC) and hydrogen peroxide (H 2 O 2 ) that trigger the bacterial SOS response. Although the genetic regulatory mechanism associated with artAB expression is not characterized, it is thought to be associated with prophage induction, which occurs when the RecA-mediated SOS response is triggered. Here we show that subinhibitory concentration of quinolone antibiotics that are SOS-inducing agents, also induce ArtAB production in these Salmonella strains. Both MTC and fluoroquinolone antibiotics such as enrofloxacin-induced artA and recA transcription and artAB-encoding prophage (ArtAB-prophage) in DT104 and S. Worthington. However, in S. bongori, which harbours artAB genes on incomplete prophage, artA transcription was induced by MTC and enrofloxacin, but prophage induction was not observed. Taken together, these results suggest that SOS response followed by induction of artAB transcription is essential for ArtAB production. H 2 O 2 -mediated induction of ArtAB prophage and efficient production of ArtAB was observed in DT104 but not in S. Worthington and S. bongori. Therefore, induction of artAB expression with H 2 O 2 is strain-specific, and the mode of action of H 2 O 2 as an SOS-inducing agent might be different from those of MTC and quinolone antibiotics.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of SOS-inducing agents on the expression of ArtAB toxin gene in Salmonella enterica and Salmonella bongori

et al. 2020

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“…Conversely, PT ADP-ribosylates the inhibitory Giα at cysteine 351 residue, which locks the Giα in GDP-bound inactive state, thus leading to a constitutive active cAMP signalling [195][196][197]. Similar cytotoxic effects have been also described for additional PT-like toxins recently characterised from several Salmonella species such as S. typhimurium (ArtAB-DT104), S. worthington (ArtAB-SW) and S. bongori (ArtAB-Sb) [139,198].…”

Section: Cholera Toxin-likementioning

confidence: 86%

“…Bacterial as well as eukaryotic ARTCs are well known to MARylate protein substrates onto basic amino acid residue arginine through Nglycosidic bonds, however other residues have been identified as targets of bARTC, such as cysteine, threonine, asparagine and glutamate [136][137][138][139][140][141][142]. Instead, bARTDs selectively MARylate post-translationally modified histidine residues, termed diphtamide, in protein substrates (please refer to 4.1.2 for further details).…”

Section: Amino Acids Modified By Adprmentioning

confidence: 99%

Targeting ADP-ribosylation as an antimicrobial strategy

Catara

Corteggio

Valente

et al. 2019

Biochemical Pharmacology

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A B S T R A C T ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.T large number of worldwide spread diseases, affecting humans, insects and plants [31,[56][57][58], with a great impact on human health. In addition, infectious diseases strongly affect the world economy in terms of costs for the human health as well as food and agricultural economic losses [59]. The use of antibiotics to counteract the pathogen infections has represented the therapeutic strategy of choice in the last century, however the emergence of antibiotic resistance strains represents the major challenge of the 21st century [60][61][62]. Targeting bacterial pathogenic mechanisms by disarming pathogens of virulence factors, for instance by inhibiting the enzymatic activity of bART, represents a valid alternative intervention strategy to overcome antibiotic resistance [63][64][65][66]. In addition, because of the conservation of ADPr systems throughout the evolution, the understanding of bacterial pathogenic mechanisms may contribute to unveil novel and conserved cellular processes regulated by ADPr in high organisms [34,45,67,68]. The dysregulation of such processes can be either cause of human diseases or be target of therapeutic intervention [39,[69][70][71].Herein, we will provide a summary of bacterial ADPr systems describing their pathogenic mechanisms and highlighting the similarities with ADPr systems in mammals as well. Further, we discuss the potential of targeting ADPr for therapeutic strategies of infection diseases. ADP-ribosylation in pathophysiologyADPr was originally described in the 60s; two independent studies reported the identification of a new polymer, poly(ADP-ribose) (PAR) synthesised from NAD + in vertebrate cells [72] and, simultaneously, the finding that bacterial DTX activity from C. diphteriae is dependent on NAD + content [73]. In the following decades, research in the field has expanded the involvement of ADPr ...

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“…Here we show that the majority of S. Javiana isolates also encode the artAB operon (95% of the isolates examined here). Interestingly, at least 25 other serovars have also been shown to encode artAB (Rodriguez-Rivera et al, 2015;Tamamura et al, 2017). In this study, some of the S. Javiana isolates harbored artB with a 46 bp internal deletion, which could reflect either acquisition of a mutated artB or slipped-strand mispairing that occurred during DNA replication, which has been reported previously for promoting phenotypic diversity in bacterial pathogens such as B. pertussis (Decker et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

The Typhoid Toxin Produced by the Nontyphoidal Salmonella Serovar Javiana Can Utilize Multiple Binding Subunits, which Compete for Inclusion in the Holotoxin

Gaballa

Harrand

Cohn

et al. 2019

Preprint

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21Salmonella enterica encodes a wide array of virulence factors. One novel virulence 22 factor, a DNA-damaging toxin known as the typhoid toxin (TT), was recently characterized 23 in >40 nontyphoidal Salmonella (NTS) serovars. Interestingly, these NTS serovars, including 24 S. enterica subsp. enterica serovar Javiana, also encode artB, a homolog of the binding 25 subunit (PltB) of the TT. Here, we show that ArtB and PltB compete for inclusion in the 26 pentameric binding subunit of the TT. Using a combination of in silico modeling, a bacterial 27 two-hybrid system expressed in S. Javiana, and tandem affinity purification (TAP) of the 28 holotoxin subunits, we show that ArtB and PltB interact in vivo. Furthermore, binding 29 subunits composed of homo-and heteropentamers of ArtB and PltB are able to associate with 30 CdtB and PltA to form biologically active toxins. As artB was, (i) conserved among S. 31 Javiana isolates, and (ii) co-expressed with pltB and cdtB under Mg 2+ -limiting conditions, we 32 hypothesized that ArtB and PltB compete for inclusion in the binding subunit. Using a novel 33 competition assay, we show that PltB outcompetes ArtB for inclusion in the binding subunit, 34 when cultured at neutral pH. Together, our results suggest that the TT produced by S. Javiana 35 utilizes multiple configurations of the binding subunit, representing a novel toxin form and 36 adaptation mechanism for the AB5 toxin family. Our work suggests that Salmonella serovars, 37 including S. Javiana, evolved to encode and maintain multiple binding subunits that can be 38 used to form an active toxin, which may enhance the variety of cells, tissues, or hosts 39 susceptible to this novel form of the TT. 40Difco Lennox broth pH 7 (LB; Becton Dickinson [BD], Franklin Lakes, NJ). For two-hybrid 82 system interactions, E. coli and S. Javiana strains were grown in M63 medium with maltose 83 as the sole carbon source (Battesti and Bouveret, 2012). N-salts minimal medium (pH 5.8 or 84 7) containing 8 µM MgSO4 (Deiwick et al., 1999) was used for experiments assessing RNA 85 transcript levels. Unless otherwise indicated, ampicillin and kanamycin were used at 100 86 µg/mL and 50 µg/mL, respectively, in complex medium (LB) and 50 µg/mL and 25 µg/mL, 87 respectively, in chemically defined medium (M9 or N-salts minimal media). 88 Human intestinal epithelial cells (HIEC-6 cells; ATCC, Manassas, VA), (Perreault 89 and Beaulieu, 1996), were routinely cultured in Opti-MEM (Gibco-Invitrogen, Carlsbad, CA) 90 medium supplemented with 10% (v/v) fetal bovine serum (FBS; Gibco-Invitrogen) and 91 4recombinant epidermal growth factor (10 ng/ml; Gibco-Invitrogen) at 37°C with 5% CO2. 92Cell supernatants were tested routinely for Mycoplasma spp. and Acheoplasma spp. infection 93 using the VenorGEM Mycoplasma detection kit (Sigma-Aldrich, St. Louis, MO). 94Cloning and expression of toxin proteins in E. coli 95 To express CdtB, PltA, PltB, and ArtB, we cloned and expressed the following 96 constructs in E. coli BTH101 cells (Karimova et al.,...

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Characterization of pertussis-like toxin from Salmonella spp. that catalyzes ADP-ribosylation of G proteins

Cited by 28 publications

References 38 publications

Influence of SOS-inducing agents on the expression of ArtAB toxin gene in Salmonella enterica and Salmonella bongori

Influence of SOS-inducing agents on the expression of ArtAB toxin gene in Salmonella enterica and Salmonella bongori

Targeting ADP-ribosylation as an antimicrobial strategy

The Typhoid Toxin Produced by the Nontyphoidal Salmonella Serovar Javiana Can Utilize Multiple Binding Subunits, which Compete for Inclusion in the Holotoxin

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