Elodie Lesne

Public Health England | HPA · HPA Microbiology Services, Porton Down

Complement is a key component of functional immunological assays used to evaluate vaccine-mediated immunity to a range of bacterial and viral pathogens. However, standardization of these assays is complicated due to the availability of a human complement source that lacks existing antibodies acquired either through vaccination or natural circulatio...

The two-component system BvgAS controls the virulence regulon in Bordetella pertussis . BvgS is the prototype of a family of sensor histidine-kinases harboring periplasmic Venus flytrap (VFT) domains. The VFT domains are connected to the cytoplasmic kinase moiety by helical linkers separated by a Per-ARNT-Sim (PAS) domain. Antagonism between the tw...

Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune r...

The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg+ phase to avirulent Bvg- or intermediate Bvgi phases, in whic...

Bordetella pertussis controls the expression of its virulence regulon through the two-component system BvgAS. BvgS is a prototype for a family of multidomain sensor kinases. In BvgS, helical linkers connect periplasmic Venus flytrap (VFT) perception domains to a cytoplasmic Per-Arnt-Sim (PAS) domain and the PAS domain to the dimerization/histidine...

The whooping cough agent, Bordetella pertussis, controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Si...

ARRIVE guidelines checklist. (DOCX)

The whooping cough agent Bordetella pertussis controls the expression of its large virulence regulon in a coordinated manner through the two-component signal transduction system BvgAS. In addition to the genes coding for bona fide virulence factors, the Bvg regulon comprises genes of unknown function. In this work, we characterized a new Bvg-activa...

Bordetella pertussis est l’agent responsable de la coqueluche. Pour coloniser le tractus respiratoire humain, cette bactérie à Gram négatif, aérobie stricte, produit de nombreux facteurs de virulence dont l’expression est sous la dépendance du système à deux composants BvgAS. BvgS est un senseur-kinase dimérique. Chaque monomère est constitué de tr...

The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that prece...

Detection of the inactive BvgS variants in B. pertussis. Immunoblot analyses of BvgS variants (indicated by an arrow) in membrane extracts of B. pertussis with no or little activity. The avirulent, ΔbvgA strain was used as a control to show the abundance of BvgS in an avirulent strain. The loading control is an unidentified B. pertussis protein for...

Supplemental methods. Construction of the plasmids used in this work. Protein sequence analyses. Download

Characterization of the BvgS Cys variants. (A) Intradimer S-S formation for BvgSt with its two natural Cys residues (WT) and for its variants harboring the Cys607Ala-plus-Cys881Ser, Cys607Ala, or Cys881Ser substitution under basal conditions (−) or after the addition of 5 mM chloronicotinate (+). The monomeric and dimeric forms of the BvgSt variant...

Deletion of the PAS domain affects BvgS function. (A) Sequence alignment of the three BvgS variants harboring deletion of the PAS domain and the wt BvgS. Note that in the variants, the Glu701 residue of BvgS was replaced with Gly, as in sensor kinase PP3413 of Pseudomonas putida. (B) Determination of the activities of BvgS variants harboring PAS de...

Activities of specific variants using the fhaB-lacZ reporter system. (A) BvgS variants with Ala-to-Leu substitutions. (B) BvgSΔPAS-R1 variants. The means and standard errors of the means are given. Download

Interaction energies of 2-HCC in PAS-less BvgS variants determined in silico. The average values of pseudoenergy of interaction per residue were calculated from 10 models of coiled coil for each variant (ΔPAS-R1 to -R4), and the errors of the means are given. Download

The two-component sensory transduction system BvgAS controls the virulence regulon of the whooping-cough agent Bordetella pertussis. The periplasmic moiety of the homodimeric sensor kinase BvgS is composed of four bilobed Venus flytrap (VFT) perception domains followed by α helices that extend into the cytoplasmic membrane. In the virulent phase, t...

The two-component sensory transduction system BvgAS controls the virulence regulon of the whooping-cough agent Bordetella pertussis. The periplasmic moiety of the homo-dimeric sensor-kinase BvgS is composed of four bilobed Venus flytrap (VFT) perception domains followed by α helices that extend into the cytoplasmic membrane. In the virulent phase,...

TpsB proteins are Omp85 superfamily members that mediate protein translocation across the outer membrane of Gram-negative bacteria. Omp85 transporters are composed of N-terminal POTRA domains and a C-terminal transmembrane β-barrel. In this work, we track the in vivo secretion path of the Bordetella pertussis filamentous haemagglutinin (FHA), the s...