Mutations in the linker region of Bvgs abolish response to environmental signals for the regulation of the virulence factors in bordetella pertussis

Manetti, Riccardo; Aricò, Beatrice; Rappuoli, Rino; Scarlato, Vincenzo

doi:10.1016/0378-1119(95)94961-k

Cited by 9 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutational analyses by ourselves and others (Goyard et al, 1994;Manetti et al, 1994) insensitive to modulating signals. These mutations map to the linker region of BvgS and are dominant to periplasmic mutations.…”

Section: Discussionmentioning

confidence: 90%

Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica

Tejada

Miller

Cotter

1996

Molecular Microbiology

107

160

View full text Add to dashboard Cite

Bordetella pertussis and Bordetella bronchiseptica contain nearly identical BvgAS signal-transduction systems that mediate a biphasic transition between virulent (Bvg+) and avirulent (Bvg-) phases. In the Bvg+ phase, the two species express a similar set of adhesins and toxins, and in both organisms the transition to the Bvg- phase occurs in response to the same environmental signals (low temperature or the presence of nicotinic acid or sulphate anion). These two species differ, however, with regard to Bvg(-)-phase phenotypes, host specificity, the severity and course of the diseases they cause, and also potentially in their routes of transmission. To investigate the contribution of the virulence-control system to these phenotypic differences, we constructed a chimeric B. bronchiseptica strain containing bvgAS from B. pertussis and compared it with wild-type B. bronchiseptica in vitro and in vivo. The chimeric strain was indistinguishable from the wild type in its ability to express Bvg(+)- and Bvg(-)- phase-specific factors. However, although the chimeric strain responded to the same signals as the wild type, it differed dramatically in sensitivity to these signals; significantly more nicotinic acid or MgSO4 was required to modulate the chimeric strain compared with the wild-type strain. Despite this difference in signal sensitivity, the chimeric strain was indistinguishable from the wild type in its ability to cause respiratory-tract infections in rats, indicating that the bvgAS loci of B. pertussis and B. bronchiseptica are functionally interchangeable in vivo. By exchanging discrete fragments of bvgAS, we found that the periplasmic region of BvgS determines signal sensitivity.

show abstract

Section: Discussionmentioning

confidence: 90%

Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica

Tejada

Miller

Cotter

1996

Molecular Microbiology

107

160

View full text Add to dashboard Cite

show abstract

“…Genetic evidence supports the idea that BvgS is the major effector of BvgA phosphorylation. The bvgS gene is the locus affected by mutations that result in a variety of phenotypes, including a null phenotype, resistance to modulation, and the intermediate phase phenotype (Miller et al ., ; Goyard et al ., ; Manetti et al ., ; Cotter and Miller, ). However it is not known if any other B. pertussis factors can phosphorylate BvgA.…”

Section: Resultsmentioning

confidence: 99%

In vivo phosphorylation dynamics of the Bordetella pertussis virulence‐controlling response regulator BvgA

Boulanger

Chen

Hinton

et al. 2013

Molecular Microbiology

View full text Add to dashboard Cite

Summary We have used protein electrophoresis through polyacrylamide gels derivatized with the proprietary ligand Phos-tag™ to separate the response regulator BvgA from its phosphorylated counterpart BvgA~P. This approach has allowed us to readily ascertain the degree of phosphorylation of BvgA in in vitro reactions, or in crude lysates of Bordetella pertussis grown under varying laboratory conditions. We have used this technique to examine the kinetics of BvgA phosphorylation after shift of B. pertussis cultures from non-permissive to permissive conditions, or of its dephosphorylation following a shift from permissive to non-permissive conditions. Our results provide the first direct evidence that levels of BvgA~P in vivo correspond temporally to the expression of early and late BvgA-regulated virulence genes. We have also examined a number of other aspects of BvgA function predicted from previous studies and by analogy with other two component response regulators. These include the site of BvgA phosphorylation, the exclusive role of the cognate BvgS sensor kinase in its phosphorylation in Bordetella pertussis, and the effect of the T194M mutation on phosphorylation. We also detected the phosphorylation of a small but consistent fraction of BvgA purified after expression in Escherichia coli.

show abstract

“…BvgS has a periplasmic region and several distinct cytoplasmic domains: the linker, transmitter, receiver and C-terminus ( Figure 1). The BvgS linker is the site of mutations that render BvgS insensitive to environmental signals Goyard et al, 1994;Manetti et al, 1994). The transmitter of BvgS contains a conserved histidine (His729) which is the proposed site of autophosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Integration of multiple domains in a two-component sensor protein: the Bordetella pertussis BvgAS phosphorelay.

1996

View full text Add to dashboard Cite

BvgS and BvgA, a two‐component system, regulate virulence gene expression in Bordetella pertussis. BvgS is a transmembrane sensor protein that can autophosphorylate and phosphorylate BvgA. Phosphorylated BvgA activates transcription of virulence genes. The cytoplasmic region of BvgS contains three domains separated by alanine/proline‐rich sequences–the transmitter, receiver and C‐terminus. We report that the C‐terminal domain, like the transmitter and receiver, is an essential part of the phosphorelay from BvgS to BvgA. The BvgS C‐terminal domain is phosphorylated in trans via a phosphotransfer mechanism by the cytoplasmic portion of BvgS, and trans‐phosphorylation of the C‐terminal domain requires both the transmitter and receiver. We also demonstrate that phosphorylated, purified C‐terminal domain alone is sufficient for phosphotransfer to BvgA. A point mutation in the C‐terminal domain (His1172–>Gln) abolishes BvgS activity in vivo and eliminates detectable phosphorylation of BvgA in vitro. Activity of BvgS His 1172–>Gln could be restored by providing the wild‐type C‐terminal domain in trans. Our results indicate an obligatory role for an alternate phosphodonor module in the BvgAS phosphorelay.

show abstract

Mutations in the linker region of Bvgs abolish response to environmental signals for the regulation of the virulence factors in bordetella pertussis

Cited by 9 publications

References 0 publications

Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica

Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica

In vivo phosphorylation dynamics of the Bordetella pertussis virulence‐controlling response regulator BvgA

Integration of multiple domains in a two-component sensor protein: the Bordetella pertussis BvgAS phosphorelay.

Contact Info

Product

Resources

About