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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the pertussis toxin operon (ptx) is positively regulated in Bordetella pertussis by the bvgAS locus. However, a ptx-lacZ transcriptional fusion in Escherichia coli cannot be activated by bvgAS in trans. This suggests that an additional factor(s) is required for transcription of ptx. A gene encoding a Bvg accessory factor (Baf) was identified by its ability to activate an E. coli ptx-lacZ fusion in the presence of bvgAS. The expression of ptx-lacZ was decreased by the addition of 40 mM MgSO4, a compound that also modulates ptx expression in B. pertussis. Baf alone did not activate expression of an E. coli fhaB-lacZ fusion, nor did it increase expression of fhaB-lacZ in trans with bvgAS. The gene encoding Baf was localized, sequenced, and found to produce a novel 28-kDa protein. Sequences homologous to B. pertussis baf were identified in Bordetella bronchiseptica and Bordetella parapertussis but not in Bordetella avium. When an additional copy of baf was integrated into the chromosome of BC75, a B. pertussis mutant that produces a low level of pertussis toxin, pertussis toxin production was partially complemented in the cointegrate strain.
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PMID:Identification of a Bordetella pertussis regulatory factor required for transcription of the pertussis toxin operon in Escherichia coli. 760 46

The influence was investigated of DNA gyrase-inhibiting drugs on the expression of various genes of Bordetella pertussis. We show that the promoters of the virulence regulatory bvg locus and of several bvg-regulated virulence factors, such as the fha, ptx, cya, fim2 and vrg6 loci are very sensitive to the action of novobiocin and coumermycin A, as reflected by transcriptional differences in gene expression. Inhibition of DNA gyrase by the drugs led to a strong decrease in transcription of these genes. Interestingly, one gene belonging to the bvg virulence regulon behaved differently: the promoter of the prn locus, coding for the outer membrane protein pertactin, involved in bacterial adhesion to eukaryotic cells, was induced after inhibition of DNA gyrase. The expression of other genes not belonging to the bvg regulon, such as those encoding porin (POR) and superoxide dismutase (SodB), were not, or only weakly, affected by the drugs. This demonstrates that with respect to drug-induced changes in DNA supercoiling there exist different types of promoters in B. pertussis. In an attempt to identify additional regulatory mechanisms that may modulate virulence gene expression, we investigated the effect of various environmental stimuli on the stability of the bvg-regulated vrg6 and the bvg-independent sodB transcripts. We found that some signals transduced via by the BvgS sensor protein, such as variations in the growth temperature or the presence of nicotinic acid, exerted a strong effect on the half life of these transcripts, whereas another modulating agent, MgSO4, did not have any influence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Global regulatory mechanisms affect virulence gene expression in Bordetella pertussis. 771 7

In Bordetella pertussis, the coordinate regulation of virulence factor expression is controlled by the products of the bvgAS locus. In the presence of modulating signals such as MgSO4, nicotinic acid, or reduced temperature, the expression of bvg-activated genes is reduced while the expression of bvg-repressed genes is induced. One model for the regulation of bvg-repressed genes predicts the existence of a repressor protein encoded by a bvg-activated gene. Once activated, the product of this bvg-activated gene would bind to and repress transcription from the bvg-repressed genes. We isolated five genetically independent transposon insertion mutants of B. pertussis that have a phenotype consistent with the knockout of a putative bvg-regulated repressor. These mutants constitutively expressed a vrg6-phoA transcriptional fusion but demonstrated normal bvgAS function. Genomic mapping and DNA sequence analysis of the sites of transposon insertion demonstrated that these mutants define a locus downstream of bvgAS. Introduction of an in-frame, 12-bp insertion within this locus also conferred the mutant phenotype, confirming that the phenotype seen in the transposon mutants is the result of disruption of a distinct gene, which we have designated bvgR, and is not a consequence of polar effects on bvgAS.
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PMID:Identification of a locus required for the regulation of bvg-repressed genes in Bordetella pertussis. 775 Dec 82

Expression of virulence factors of Bordetella pertussis is coordinately regulated by the products of the bvg locus, which codes for a sensory protein (BvgS) and a positive regulator of transcription (BvgA), a pair in the family of bacterial 'two-component' regulators. Transcription of the bvg-regulated promoters is repressed by modulating environmental factors such as 50 mM MgSO4, 10 mM nicotinic acid (NA) or low temperature (25 degrees C). We have isolated a spontaneous mutant (SK170) which expresses virulence genes at either 25 degrees C, or in the presence of 1-5 mM NA, or 10-50 mM MgSO4. Virulence factors in strain SK170 are still repressed by higher concentrations of NA (10 mM), or by a combination of low temperature (25 degrees C) and one of the other modulating agents. From this strain, we have isolated a second mutant (SK180) that showed constitutive synthesis of the virulence factors under any growth regime. Nucleotide (nt) and deduced amino acid (aa) sequence analysis showed that SK170 contains a substitution at aa570 of BvgS and SK180 contains an additional substitution at aa680. These substitutions are confined to a 161-aa sequence that links the transmembrane (TM) and kinase domains of BvgS. These mutations also alter the transcriptional autoregulation of the P1 and P2 promoters of the bvg locus. P1, which in the wild-type (wt) strain is repressed by modulating agents, is constitutively active in the mutant strains. On the contrary, P2, which is normally induced by all three modulating agents, is active in strain SK170 only in the presence of MgSO4 or NA, while in strain SK180 this promoter is repressed by modulating agents. The mutants exhibit elevated levels of the BvgA regulatory protein and have a virulent phenotype also in the presence of modulating agents.
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PMID:Mutations in the linker region of BvgS abolish response to environmental signals for the regulation of the virulence factors in Bordetella pertussis. 795 37

We cloned and sequenced two Escherichia coli genes which are members of a family of an environmentally responsive two-component system. The nucleotide (nt) and deduced amino-acid sequences of these two genes were found to be homologous to those of the Bordetella pertussis bvgA and bvgS genes. They were mapped at 51 min (clones 6B9 to 7G9 of the Kohara miniset library of the E. coli chromosome). Both proteins, deduced from their nt sequences, were identified in the coupled in vitro transcription-translation system; their molecular masses were consistent with BvgA and BvgS (23 and 135 kDa, respectively). Furthermore, when these genes were expressed on a multicopy plasmid in an envZ deletion strain, ompC expression was induced. This expression was found to be regulated by low temperature, MgSO4 and nicotinic acid, factors known to control the virulence of B. pertussis via BvgA and BvgS. These results indicate that the newly cloned genes were structurally and functionally similar to bvgA and bvgS, and we designated these genes evgA and evgS.
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PMID:Newly identified genes involved in the signal transduction of Escherichia coli K-12. 812 43

Five TnphoA fusions to vir-repressed genes (vrg genes) have been identified in the respiratory pathogen Bordetella pertussis. A comparison of vrg DNA sequences suggests a consensus DNA element within the coding regions of four of five vrg genes. To determine the role of this DNA sequence in vrg regulation, a nucleotide substitution mutation in the conserved region of vrg-6 was isolated. This mutant showed constitutively high levels of expression in the absence of antigenic modulators, MgSO4 and nicotinic acid, suggesting that this DNA element may be a control site for vrg repression. Moreover, Northern (RNA) analysis and transcriptional fusion analysis suggest that vrg genes are regulated at the transcriptional level. To determine whether sequences in the coding region were sufficient to respond to antigenic modulation, a vrg-6::TnphoA promoter deletion plasmid that contained a heterologous promoter driving the expression of vrg-6 coding sequences from the vrg-6 translation start site to the TnphoA fusion junction was constructed. This heterologous construct responded to modulators in a vir-dependent fashion, indicating that sequences upstream of the coding sequence are not required for antigenic modulation. Southwestern (DNA-protein) analysis and mutational studies suggest that the vrg consensus DNA sequence is specifically recognized by a 34-kDa vir-activated gene (vag) product, whose binding results in down-regulation of vrg transcript levels. We conclude, at least for the vrg::TnphoA fusion strains, that a site on the DNA that corresponds to a consensus sequence located in the vrg coding region is sufficient to confer the transcriptional regulation (repression) of vrg genes when B. pertussis strains are grown under nonmodulating conditions.
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PMID:Repressor binding to a regulatory site in the DNA coding sequence is sufficient to confer transcriptional regulation of the vir-repressed genes (vrg genes) in Bordetella pertussis. 841 98

With DNA probes derived from the fimbrial subunit genes fim2 and fim3 of Bordetella pertussis, two homologous subunit genes of Bordetella bronchiseptica were identified and cloned. The nucleotide sequences of these genes were determined. Comparison of these nucleotide sequences with the B. pertussis fimbrial fim2 and fim3 subunit genes showed a pronounced homology. Therefore, the B. bronchiseptica genes were also designated fim2 and fim3. Expression of the two B. bronchiseptica genes was demonstrated by Western blotting (immunoblotting) with polyclonal antiserum directed against the Fim2 and Fim3 fimbrial subunit proteins of B. pertussis and by enzyme-linked immunosorbent assay with monoclonal antibodies. After growth of B. bronchiseptica in the presence of MgSO4, no expression of both fimbrial subunit genes was observed. While no fimbriae were expressed, expression of flagella was observed under these circumstances. A longer C-stretch (up to 19 cytosine residues) than the one in front of the fim2 and fim3 genes of B. pertussis is present in front of the B. bronchiseptica fimbrial genes. In adherence experiments, fimbriated (Bvg+) as well as flagellated (Bvg-) B. bronchiseptica bacteria were able to adhere to HeLa cells, whereas nonflagellated B. pertussis did not. This suggests that fimbriae as well as other factors (possibly flagella) contribute to adherence of B. bronchiseptica to eukaryotic cells.
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PMID:Characterization of the fim2 and fim3 fimbrial subunit genes of Bordetella bronchiseptica: roles of Fim2 and Fim3 fimbriae and flagella in adhesion. 894 52

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.
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PMID:Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica. 897 11

BvgAS is a two-component system of Bordetella pertussis involved in the reciprocal regulation of the virulence genes and the flagellar biosynthesis. In this study, we found that expression of bvgAS in Escherichia coli also results in reduced motility. The repression was relieved by the addition of known chemical modulators of BvgAS such as MgSO4 and nicotinic acid, indicating that functional BvgAS proteins are required for the negative control of E. coli motility. In addition, BvgAS repressed the transcription of the flhDC master operon of E. coli, which consequently caused non-flagellation on the cell surface. However, expression of BvgAS had no effect on stress-resistant motile mutants of E. coli. These data suggest that E. coli may have BvgA-like protein(s) involved in the regulatory interactions between the stress response and the flagellar biosynthesis.
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PMID:Expression of bvgAS of Bordetella pertussis represses flagellar biosynthesis of Escherichia coli. 991 10

Whooping cough still represents a major health problem, despite the use of effective vaccines for several decades. Being classically a typical childhood disease, whooping cough in young adults is now more common than it used to be, suggesting that protection after vaccination wanes during adolescence. As an alternative to the current vaccines, we wish to develop live attenuated vaccines to be delivered by the nasal route, such as to mimic the natural route of infection and to induce long lasting immunity. Bordetella pertussis, the etiological agent of whooping cough, produces a number of virulence factors, including toxins. Its recently determined genome sequence makes it now possible to apply functional genomics, such as transcriptomics and systematic knock-out mutagenesis. The expression of most known B. pertussis virulence genes is controlled by the two-component system BvgA/S. DNA microarray analyses have led to the identification of novel genes in the BvgA/S regulon, some of which are activated by BvgA/S and others are repressed by BvgA/S. In addition, some genes appear to be differentially modulated by nicotinic acid and MgSO4, both known to modulate the expression of BvgA/S-regulated genes. Among others, the functional genomics approach has uncovered two strongly BvgA/S-activated genes, named hotA and hotB (for 'homolog of toxin'), the products of which show high sequence similarities to pertussis toxin subunits. The identification of the full array of virulence factors, as well as an integrated understanding of the bacterial physiology should allow us to design attenuated B. pertussis strains useful for intranasal vaccination. A first generation of attenuated strains has already shown full protection in mice after a single intranasal administration. Such strains may also serve as vaccine carriers for heterologous antigens, in order to vaccinate against several different pathogens simultaneously.
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PMID:Bordetella pertussis from functional genomics to intranasal vaccination. 1514 35


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