The Bordetella pertussis model of exquisite gene control by the global transcription factor BvgA

Decker, Kimberly Baxter; James, Tamara D.; Stibitz, Scott; Hinton, Deborah M.

doi:10.1099/mic.0.058941-0

Cited by 48 publications

(39 citation statements)

References 89 publications

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“…BvgS is a transmembrane sensor kinase that upon activation mediates a complex phospho-transfer cascade [24], resulting in the phosphorylation of BvgA, whose level is believed to drive the expression of the virulence activated genes [25]. B. pertussis can thus be grown under different virulence phases defined by the expression of different subsets of genes.…”

Section: The Virulence Determinants Of B Pertussismentioning

confidence: 99%

“…Besides the positive BvgAS regulation, B. pertussis is subjected to another level of control of fim2 and fim3 expression. The promoter regions of fim2 and fim3 both contain homopolymeric tracts of cytosine (c-tract) that overlap their -35 regions and are responsible for slipped-strand mispairing during replication [25], leading to insertion or deletion of new cytosine. Each promoter thus only enables the transcription of its downstream gene when this c-tract is of permissive length, suggesting that these cytosines act as spacers for correct induction of the gene transcription upon binding of phosphorylated BvgA~P and recruitment of the transcriptional machinery.…”

Section: The B Pertussis Los Endotoxinmentioning

confidence: 99%

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Bordetella pertussisand pertactin-deficient clinical isolates: lessons for pertussis vaccines

Hégerlé

Guiso²

2014

Expert Review of Vaccines

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Bordetella pertussis causes whooping cough in humans, a highly transmissible respiratory disease life threatening for unvaccinated infants. Vaccination strategies were thus introduced worldwide with great success in developed countries reaching high vaccine coverage with efficacious vaccines. In the late 20th/early 21st century, acellular pertussis vaccines replaced whole cell pertussis vaccines but B. pertussis still circulates and evolves in humans, its only known reservoir. The latest transformation of this pathogen, and of its close relative Bordetella parapertussis, is the loss of pertactin production, a virulence factor included in different acellular pertussis vaccines. The real impact of this evolution on acellular pertussis vaccines efficacy and effectiveness should be assessed through standardized surveillance and isolation of B. pertussis and B. parapertussis worldwide.

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Section: The Virulence Determinants Of B Pertussismentioning

confidence: 99%

Section: The B Pertussis Los Endotoxinmentioning

confidence: 99%

Bordetella pertussisand pertactin-deficient clinical isolates: lessons for pertussis vaccines

Hégerlé

Guiso²

2014

Expert Review of Vaccines

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“…While not depicted, the HsrA DNA binding motif in the oorDABC promoter region also spanned the Ϫ35 hexamer sequence (positions Ϫ52 to Ϫ21 relative to the transcription start site). By binding near or overlapping the Ϫ35 sequences of regulated genes, HsrA might function like a bacterial class II transcriptional activator by interacting with the housekeeping sigma factor RpoD or with the ␣-C-terminal domain (␣CTD) of RNA polymerase to initiate transcription (61). While our studies do not rule out the possibility that other DNA binding proteins may participate in regulation of porGDAB or oorDABC, they do support a prominent role for the homeostatic regulator HsrA as a positive regulator of transcription and establish a strong correlation between HsrA levels and those of PFOR, TlpB (Fig.…”

Section: Figmentioning

confidence: 99%

Response to Metronidazole and Oxidative Stress Is Mediated through Homeostatic Regulator HsrA (HP1043) in Helicobacter pylori

et al. 2014

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Metronidazole (MTZ) is often used in combination therapies to treat infections caused by the gastric pathogen Helicobacter pylori.Resistance to MTZ results from loss-of-function mutations in genes encoding RdxA and FrxA nitroreductases. MTZ-resistant strains, when cultured at sub-MICs of MTZ (5 to 20 g/ml), show dose-dependent defects in bacterial growth; depressed activities of many Krebs cycle enzymes, including pyruvate:ferredoxin oxidoreductase (PFOR); and low transcript levels of porGDAB (primer extension), phenotypes consistent with an involvement of a transcriptional regulator. Using a combination of protein purification steps, electrophoretic mobility shift assays (EMSAs), and mass spectrometry analyses of proteins bound to porG promoter sequences, we identified HP1043, an essential homeostatic global regulator (HsrA [for homeostatic stress regulator]). Competition EMSAs and supershift analyses with HsrA-enriched protein fractions confirmed specific binding to porGDAB and hsrA promoter sequences. Exposure to MTZ resulted in >10-fold decreases in levels of HsrA and in levels of the HsrA-regulated gene products PFOR and TlpB. Exposure to paraquat (PQ), hydrogen peroxide, or organic peroxides showed near equivalence with MTZ, revealing a common oxidative stress response pathway. Finally, direct superoxide dismutase (SOD) assays showed an inverse relationship between HsrA levels and SOD activity, suggesting that HsrA may serve as a repressor of sodB. As a homeostatic sentinel, HsrA appears to be ideally positioned to enable rapid shutdown of genes associated with metabolism and growth while activating (directly or indirectly) oxidative defense genes in response to low levels of toxic metabolites (MTZ or oxygen) before they reach DNA-damaging levels. Helicobacter pylori is a microaerobic bacterium that causes lifelong infections of the gastric mucosa of over 3 billion persons worldwide, and while most of these infections result in mild superficial gastritis, some infections progress to more serious diseases such as peptic and duodenal ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer (1-3). The remarkable ability of H. pylori to both colonize and persist in the gastric milieu is attributed to several systems that monitor local pH, including a novel pH-gated urea transporter (UreI) that modulates a powerful urease system (4, 5), a pH-sensing chemoreceptor (TlpB) that directs both colonization and avoidance of washout with mucus turnover (6), and a pH-sensing two-component regulatory system (ArsRS) that modulates expression of acid survival genes in sync with the daily cycling of stomach acid (7-10). In contrast to acid stress, little is known regarding the response to oxidative stress, yet H. pylori promotes gastric inflammation and the recruitment of neutrophils and macrophages, all of which produce reactive oxygen and nitrogen species (11, 12). While H. pylori responds to oxidative stress insults by increasing the expression levels of many genes, including catalase, alkyl hydroperoxide r...

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“…to cause respiratory disease, focusing on the roles and functions of virulence factors in pathogenesis. For the interested reader, more specialized recent reviews on pertussis toxin biology 19, 20 , virulence gene regulation 21 , immunity 22, 23 and vaccines 24 are available, as well as an earlier comprehensive review on Bordetella spp. pathogenesis 25 .…”

mentioning

confidence: 99%

Bordetella pertussis pathogenesis: current and future challenges

et al. 2014

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Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies.

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The Bordetella pertussis model of exquisite gene control by the global transcription factor BvgA

Cited by 48 publications

References 89 publications

Bordetella pertussisand pertactin-deficient clinical isolates: lessons for pertussis vaccines

Bordetella pertussisand pertactin-deficient clinical isolates: lessons for pertussis vaccines

Response to Metronidazole and Oxidative Stress Is Mediated through Homeostatic Regulator HsrA (HP1043) in Helicobacter pylori

Bordetella pertussis pathogenesis: current and future challenges

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