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While previous reports had suggested that the typhoid toxin (TT) could potentially use ArtB as an alternate binding subunit, this was thought to play a minor role in the evolution and biology of the toxin. In this study, we establish that both TT genes and artB are widespread among Salmonella enterica subsp. enterica , suggesting that TT likely plays a broader role in Salmonella virulence that extends beyond its proposed role in typhoid fever.
A. Gaballa; R. A. Cheng; A. S. Harrand; A. R. Cohn; M. Wiedmann. The Majority of Typhoid Toxin-Positive Salmonella Serovars Encode ArtB, an Alternate Binding Subunit. mSphere 2021, 6, 1 .
AMA StyleA. Gaballa, R. A. Cheng, A. S. Harrand, A. R. Cohn, M. Wiedmann. The Majority of Typhoid Toxin-Positive Salmonella Serovars Encode ArtB, an Alternate Binding Subunit. mSphere. 2021; 6 (1):1.
Chicago/Turabian StyleA. Gaballa; R. A. Cheng; A. S. Harrand; A. R. Cohn; M. Wiedmann. 2021. "The Majority of Typhoid Toxin-Positive Salmonella Serovars Encode ArtB, an Alternate Binding Subunit." mSphere 6, no. 1: 1.
Salmonella enterica is one of the most diverse and successful pathogens, representing a species with >2,600 serovars with a variety of adaptations that enable colonization and infection of a wide range of hosts. Fimbriae, thin hair-like projections that cover the surface of Salmonella, are thought to be the primary organelles that mediate Salmonella’s interaction with, and adherence to, the host intestinal epithelium, representing an important step in the infection process. The recent expansion in genome sequencing efforts has enabled the discovery of novel fimbriae, thereby providing new perspectives on fimbrial diversity and distribution among a broad number of serovars. In this review, we provide an updated overview of the evolutionary events that shaped the Salmonella chaperone-usher fimbriome in light of recent phylogenetic studies describing the population structure of Salmonella enterica. Furthermore, we discuss the complexities of the chaperone-usher fimbriae-mediated host-pathogen interactions and the apparent redundant roles of chaperone-usher fimbriae in host and tissue tropism.
Rachel A. Cheng; Martin Wiedmann. Recent Advances in Our Understanding of the Diversity and Roles of Chaperone-Usher Fimbriae in Facilitating Salmonella Host and Tissue Tropism. Frontiers in Cellular and Infection Microbiology 2021, 10, 1 .
AMA StyleRachel A. Cheng, Martin Wiedmann. Recent Advances in Our Understanding of the Diversity and Roles of Chaperone-Usher Fimbriae in Facilitating Salmonella Host and Tissue Tropism. Frontiers in Cellular and Infection Microbiology. 2021; 10 ():1.
Chicago/Turabian StyleRachel A. Cheng; Martin Wiedmann. 2021. "Recent Advances in Our Understanding of the Diversity and Roles of Chaperone-Usher Fimbriae in Facilitating Salmonella Host and Tissue Tropism." Frontiers in Cellular and Infection Microbiology 10, no. : 1.
Although Paenibacillus species isolates are frequently isolated from pasteurized fluid milk, the link between the genetic diversity and phenotypic characteristics of these isolates was not well understood, especially as some Bacillales isolated from milk are unable to grow at refrigeration temperatures. Our data demonstrate that Paenibacillus spp. isolated from fluid milk represent tremendous interspecies diversity, with P. odorifer being the predominant Paenibacillus sp. isolated. Furthermore, genetic and phenotypic data support that P. odorifer is well suited to transition from a soil-dwelling environment, where nitrogen fixation (and other nitrate/nitrite reduction pathways present only in clade A) may facilitate growth, to fluid milk, where its multiple cold shock-associated adaptations enable it to grow at refrigeration temperatures throughout the storage of milk. Therefore, efforts to reduce bacterial contamination of milk will require a systematic approach to reduce P. odorifer contamination of raw milk.
Sarah M. Beno; Rachel A. Cheng; Renato H. Orsi; Diana R. Duncan; Xiaodong Guo; Jasna Kovac; Laura M. Carroll; Nicole H. Martin; Martin Wiedmann. Paenibacillus odorifer, the Predominant Paenibacillus Species Isolated from Milk in the United States, Demonstrates Genetic and Phenotypic Conservation of Psychrotolerance but Clade-Associated Differences in Nitrogen Metabolic Pathways. mSphere 2020, 5, 1 .
AMA StyleSarah M. Beno, Rachel A. Cheng, Renato H. Orsi, Diana R. Duncan, Xiaodong Guo, Jasna Kovac, Laura M. Carroll, Nicole H. Martin, Martin Wiedmann. Paenibacillus odorifer, the Predominant Paenibacillus Species Isolated from Milk in the United States, Demonstrates Genetic and Phenotypic Conservation of Psychrotolerance but Clade-Associated Differences in Nitrogen Metabolic Pathways. mSphere. 2020; 5 (1):1.
Chicago/Turabian StyleSarah M. Beno; Rachel A. Cheng; Renato H. Orsi; Diana R. Duncan; Xiaodong Guo; Jasna Kovac; Laura M. Carroll; Nicole H. Martin; Martin Wiedmann. 2020. "Paenibacillus odorifer, the Predominant Paenibacillus Species Isolated from Milk in the United States, Demonstrates Genetic and Phenotypic Conservation of Psychrotolerance but Clade-Associated Differences in Nitrogen Metabolic Pathways." mSphere 5, no. 1: 1.
A number of pathogenic bacteria utilize toxins to mediate disease in a susceptible host. The foodborne pathogen Salmonella is one of the most important and well-studied bacterial pathogens. Recently, whole genome sequence characterizations revealed the presence of multiple novel ADP-ribosylating toxins encoded by a variety of Salmonella serovars. In this review, we discuss both the classical (SpvB) and novel (typhoid toxin, ArtAB, and SboC/SeoC) ADP-ribosylating toxins of Salmonella, including the structure and function of these toxins and our current understanding of their contributions to virulence.
Rachel A. Cheng; Martin Wiedmann. The ADP-Ribosylating Toxins of Salmonella. Toxins 2019, 11, 416 .
AMA StyleRachel A. Cheng, Martin Wiedmann. The ADP-Ribosylating Toxins of Salmonella. Toxins. 2019; 11 (7):416.
Chicago/Turabian StyleRachel A. Cheng; Martin Wiedmann. 2019. "The ADP-Ribosylating Toxins of Salmonella." Toxins 11, no. 7: 416.
Salmonella enterica encodes a wide array of virulence factors. One novel virulence factor, a DNA-damaging toxin known as the typhoid toxin (TT), was recently characterized in >40 nontyphoidal Salmonella (NTS) serovars. Interestingly, these NTS serovars, including S. enterica subsp. enterica serovar Javiana, also encode artB, a homolog of the binding subunit (PltB) of the TT. Here, we show that ArtB and PltB compete for inclusion in the pentameric binding subunit of the TT. Using a combination of in silico modeling, a bacterial two-hybrid system expressed in S. Javiana, and tandem affinity purification (TAP) of the holotoxin subunits, we show that ArtB and PltB interact in vivo. Furthermore, binding subunits composed of homo- and heteropentamers of ArtB and PltB are able to associate with CdtB and PltA to form biologically active toxins. As artB was, (i) conserved among S. Javiana isolates, and (ii) co-expressed with pltB and cdtB under Mg2+-limiting conditions, we hypothesized that ArtB and PltB compete for inclusion in the binding subunit. Using a novel competition assay, we show that PltB outcompetes ArtB for inclusion in the binding subunit, when cultured at neutral pH. Together, our results suggest that the TT produced by S. Javiana utilizes multiple configurations of the binding subunit, representing a novel toxin form and adaptation mechanism for the AB5 toxin family. Our work suggests that Salmonella serovars, including S. Javiana, evolved to encode and maintain multiple binding subunits that can be used to form an active toxin, which may enhance the variety of cells, tissues, or hosts susceptible to this novel form of the TT.
Ahmed Gaballa; Sophia Harrand; Alexa Cohn; Martin Wiedmann; Rachel Cheng. The Typhoid Toxin Produced by the Nontyphoidal Salmonella Serovar Javiana Can Utilize Multiple Binding Subunits, which Compete for Inclusion in the Holotoxin. 2019, 666016 .
AMA StyleAhmed Gaballa, Sophia Harrand, Alexa Cohn, Martin Wiedmann, Rachel Cheng. The Typhoid Toxin Produced by the Nontyphoidal Salmonella Serovar Javiana Can Utilize Multiple Binding Subunits, which Compete for Inclusion in the Holotoxin. . 2019; ():666016.
Chicago/Turabian StyleAhmed Gaballa; Sophia Harrand; Alexa Cohn; Martin Wiedmann; Rachel Cheng. 2019. "The Typhoid Toxin Produced by the Nontyphoidal Salmonella Serovar Javiana Can Utilize Multiple Binding Subunits, which Compete for Inclusion in the Holotoxin." , no. : 666016.
The Salmonella cytolethal distending toxin (S-CDT), first described as the “typhoid toxin” in Salmonella enterica subsp. enterica serotype Typhi, induces DNA damage in eukaryotic cells. Recent studies have shown that more than 40 nontyphoidal Salmonella (NTS) serotypes carry genes that encode S-CDT, yet very little is known about the activity, function, and role of S-CDT in NTS. Here we show that deletion of genes encoding the binding subunit ( pltB ) and a bacteriophage muramidase predicted to play a role in toxin export ( ttsA ) does not abolish toxin activity in the S-CDT-positive NTS Salmonella enterica subsp. enterica serotype Javiana. However, S. Javiana strains harboring deletions of both pltB and its homolog artB , had a complete loss of S-CDT activity, suggesting that S. Javiana carries genes encoding two variants of the binding subunit. S-CDT-mediated DNA damage, as determined by phosphorylation of histone 2AX (H2AX), producing phosphorylated H2AX (γH2AX), was restricted to epithelial cells in S and G 2 /M phases of the cell cycle and did not result in apoptosis or cell death. Compared to mice infected with a Δ cdtB strain, mice infected with wild-type S. Javiana had significantly higher levels of S. Javiana in the liver, but not in the spleen, ileum, or cecum. Overall, we show that production of active S-CDT by NTS serotype S. Javiana requires different genes ( cdtB , pltA , and either pltB or artB ) for expression of biologically active toxin than those reported for S-CDT production by S. Typhi ( cdtB , pltA , pltB , and ttsA ). However, as in S. Typhi, NTS S-CDT influences the outcome of infection both in vitro and in vivo . IMPORTANCE Nontyphoidal Salmonella (NTS) are a major cause of bacterial food-borne illness worldwide; however, our understanding of virulence mechanisms that determine the outcome and severity of nontyphoidal salmonellosis is incompletely understood. Here we show that S-CDT produced by NTS plays a significant role in the outcome of infection both in vitro and in vivo , highlighting S-CDT as an important virulence factor for nontyphoidal Salmonella serotypes. Our data also contribute novel information about the function of S-CDT, as S-CDT-mediated DNA damage occurs only during certain phases of the cell cycle, and the resulting damage does not induce cell death as assessed using a propidium iodide exclusion assay. Importantly, our data support that, despite having genetically similar S-CDT operons, NTS serotype S. Javiana has different genetic requirements than S. Typhi, for the production and export of active S-CDT.
Rachel A. Miller; Michael I. Betteken; Xiaodong Guo; Craig Altier; Gerald E. Duhamel; Martin Wiedmann. The Typhoid Toxin Produced by the Nontyphoidal Salmonella enterica Serotype Javiana Is Required for Induction of a DNA Damage Response In Vitro and Systemic Spread In Vivo. mBio 2018, 9, 1 .
AMA StyleRachel A. Miller, Michael I. Betteken, Xiaodong Guo, Craig Altier, Gerald E. Duhamel, Martin Wiedmann. The Typhoid Toxin Produced by the Nontyphoidal Salmonella enterica Serotype Javiana Is Required for Induction of a DNA Damage Response In Vitro and Systemic Spread In Vivo. mBio. 2018; 9 (2):1.
Chicago/Turabian StyleRachel A. Miller; Michael I. Betteken; Xiaodong Guo; Craig Altier; Gerald E. Duhamel; Martin Wiedmann. 2018. "The Typhoid Toxin Produced by the Nontyphoidal Salmonella enterica Serotype Javiana Is Required for Induction of a DNA Damage Response In Vitro and Systemic Spread In Vivo." mBio 9, no. 2: 1.
While some species in the Bacillus cereus group are well-characterized human pathogens (e.g., B. anthracis and B. cereus sensu stricto ), the pathogenicity of other species (e.g., B. pseudomycoides ) either has not been characterized or is presently not well understood. To provide an updated characterization of the pathogenic potential of species in the B. cereus group, we classified a set of 52 isolates, including 8 type strains and 44 isolates from dairy-associated sources, into 7 phylogenetic clades and characterized them for (i) the presence of toxin genes, (ii) phenotypic characteristics used for identification, and (iii) cytotoxicity to human epithelial cells. Overall, we found that B. cereus toxin genes are broadly distributed but are not consistently present within individual species and/or clades. After growth at 37°C, isolates within a clade did not typically show a consistent cytotoxicity phenotype, except for isolates in clade VI ( B. weihenstephanensis / B. mycoides ), where none of the isolates were cytotoxic, and isolates in clade I ( B. pseudomycoides ), which consistently displayed cytotoxic activity. Importantly, our study highlights that B. pseudomycoides is cytotoxic toward human cells. Our results indicate that the detection of toxin genes does not provide a reliable approach to predict the pathogenic potential of B. cereus group isolates, as the presence of toxin genes is not always consistent with cytotoxicity phenotype. Overall, our results suggest that isolates from multiple B. cereus group clades have the potential to cause foodborne illness, although cytotoxicity is not always consistently found among isolates within each clade. IMPORTANCE Despite the importance of the Bacillus cereus group as a foodborne pathogen, characterizations of the pathogenic potential of all B. cereus group species were lacking. We show here that B. pseudomycoides (clade I), which has been considered a harmless environmental microorganism, produces toxins and exhibits a phenotype consistent with the production of pore-forming toxins. Furthermore, B. mycoides/B. weihenstephanensis isolates (clade VI) did not show cytotoxicity when grown at 37°C, despite carrying multiple toxin genes. Overall, we show that the current standard methods to characterize B. cereus group isolates and to detect the presence of toxin genes are not reliable indicators of species, phylogenetic clades, or an isolate's cytotoxic capacity, suggesting that novel methods are still needed for differentiating pathogenic from nonpathogenic species within the B. cereus group. Our results also contribute data that are necessary to facilitate risk assessments and a better understanding as to which B. cereus group species are likely to cause foodborne illness.
Rachel A. Miller; Jiahui Jian; Sarah M. Beno; Martin Wiedmann; Jasna Kovac. Intraclade Variability in Toxin Production and Cytotoxicity of Bacillus cereus Group Type Strains and Dairy-Associated Isolates. Applied and Environmental Microbiology 2018, 84, 1 .
AMA StyleRachel A. Miller, Jiahui Jian, Sarah M. Beno, Martin Wiedmann, Jasna Kovac. Intraclade Variability in Toxin Production and Cytotoxicity of Bacillus cereus Group Type Strains and Dairy-Associated Isolates. Applied and Environmental Microbiology. 2018; 84 (6):1.
Chicago/Turabian StyleRachel A. Miller; Jiahui Jian; Sarah M. Beno; Martin Wiedmann; Jasna Kovac. 2018. "Intraclade Variability in Toxin Production and Cytotoxicity of Bacillus cereus Group Type Strains and Dairy-Associated Isolates." Applied and Environmental Microbiology 84, no. 6: 1.
Bacillus cereus group isolates that produce diarrheal or emetic toxins are frequently isolated from raw milk and, in spore form, can survive pasteurization. Several species within the B. cereus group are closely related and cannot be reliably differentiated by established taxonomical criteria. While B. cereus is traditionally recognized as the principal causative agent of foodborne disease in this group, there is a need to better understand the distribution and expression of different toxin and virulence genes among B. cereus group food isolates to facilitate reliable characterization that allows for assessment of the likelihood of a given isolate to cause a foodborne disease. We performed whole genome sequencing of 22 B. cereus group dairy isolates, which represented considerable genetic diversity not covered by other isolates characterized to date. Maximum likelihood analysis of these genomes along with 47 reference genomes representing eight validly published species revealed nine phylogenetic clades. Three of these clades were represented by a single species (B. toyonensis –clade V, B. weihenstephanensis – clade VI, B. cytotoxicus - VII), one by two dairy-associated isolates (clade II; representing a putative new species), one by two species (B. mycoides, B. pseudomycoides – clade I) and four by three species (B. cereus, B. thuringiensis, B. anthracis – clades III-a, b, c and IV). Homologues of genes encoding a principal diarrheal enterotoxin (hemolysin BL) were distributed across all, except the B. cytotoxicus clade. Using a lateral flow immunoassay, hemolysin BL was detected in 13 out of 18 isolates that carried hblACD genes. Isolates from clade III-c (which included B. cereus and B. thuringiensis) consistently did not carry hblACD and did not produce hemolysin BL. Isolates from clade IV (B. cereus, B. thuringiensis) consistently carried hblACD and produced hemolysin BL. Compared to others, clade IV was significantly (p = 0.0001) more likely to produce this toxin. Isolates from clade VI (B. weihenstephanensis) carried hblACD homologues, but did not produce hemolysin BL, possibly due to amino acid substitutions in different toxin-encoding genes. Our results demonstrate that production of diarrheal enterotoxin hemolysin BL is neither inclusive nor exclusive to B. cereus sensu stricto, and that phylogenetic classification of isolates may be better than taxonomic identification for assessment of B. cereus group isolates risk for causing a diarrheal foodborne disease.
Jasna Kovac; Rachel A. Miller; Laura M. Carroll; David J. Kent; Jiahui Jian; Sarah M. Beno; Martin Wiedmann. Production of hemolysin BL by Bacillus cereus group isolates of dairy origin is associated with whole-genome phylogenetic clade. BMC Genomics 2016, 17, 1 -16.
AMA StyleJasna Kovac, Rachel A. Miller, Laura M. Carroll, David J. Kent, Jiahui Jian, Sarah M. Beno, Martin Wiedmann. Production of hemolysin BL by Bacillus cereus group isolates of dairy origin is associated with whole-genome phylogenetic clade. BMC Genomics. 2016; 17 (1):1-16.
Chicago/Turabian StyleJasna Kovac; Rachel A. Miller; Laura M. Carroll; David J. Kent; Jiahui Jian; Sarah M. Beno; Martin Wiedmann. 2016. "Production of hemolysin BL by Bacillus cereus group isolates of dairy origin is associated with whole-genome phylogenetic clade." BMC Genomics 17, no. 1: 1-16.