Disease relevance of vrg-6

• Two of these gene fusions (vrg-6 and vrg-18) have been cloned in Escherichia coli, returned on low-copy-number plasmids to several strains of B. pertussis, and found to be regulated similarly to the fusions harbored on the chromosome [1].
• Structure of Bordetella pertussis virulence factor P.69 pertactin [2].
• Many virulence factors secreted from pathogenic Gram-negative bacteria are autotransporter proteins [3].
• cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors [4].
• A high-molecular-weight outer membrane protein of Xanthomonas oryzae pv. oryzae exhibits similarity to non-fimbrial adhesins of animal pathogenic bacteria and is required for optimum virulence [5].

High impact information on vrg-6

• Bordetella pertussis, the aetiological agent of whooping cough, coordinately regulates the expression of many virulence-associated determinants, including filamentous haemagglutinin, pertussis toxin, adenylyl cyclase toxin, dermonecrotic toxin and haemolysin [6].
• Previous studies have shown that a genetic locus, vir, is required for expression from many virulence-associated loci, and that replacing the cloned vir locus in trans can restore the virulent phase phenotype to spontaneously occurring avirulent phase strains [6].
• Genes and operons that encode bacterial virulence factors are often subject to coordinate regulation [7].
• Activation of virulence gene expression requires phosphorylation of BvgA [8].
• In Bordetella pertussis the expression of virulence factors is coordinately regulated by the BvgS and BvgA proteins, members of the bacterial two-component signal transduction family, BvgS being the transmembrane sensor and BvgA the regulator [8].

Chemical compound and disease context of vrg-6

• Bordetella pertussis and Bacillus anthracis each produce a virulence-associated, calmodulin-dependent adenylate cyclase toxin, which generates increased levels of cyclic AMP in eukaryotic cells [9].
• Furthermore, B. pertussis rpoD conferred better specificity to the E. coli RNA polymerase, allowing increased expression of the B. pertussis virulence-associated tha promoter, but could not activate the ptx and cya promoters in the E. coli UQ285 strains carrying the B. pertussis bvg locus [10].
• 0. B. pertussis isogenic mutant strains deficient in filamentous hemagglutinin or adenylate cyclase toxin were incapable of proliferation inhibition, suggesting that these virulence-associated factors are essential for this activity [11].
• Although a large amount of research on Bordetella has been generated regarding protein virulence factors, the participation of the surface lipopolysaccharide (LPS) during B. bronchiseptica infection is less understood [12].
• However, cysteine can be metabolized to sulfate, and high concentrations of sulfate can selectively inhibit transcription of the virulence factors, including pertussis toxin, via the BvgAS two-component regulatory system in a process called modulation [13].

Biological context of vrg-6

• To determine the role of this DNA sequence in vrg regulation, a nucleotide substitution mutation in the conserved region of vrg-6 was isolated [14].
• 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 [14].
• We observed a 21-base palindromic sequence overlapping an 8-base direct repeat within the signal sequence coding region of vrg-6; insertion of a 6-bp linker in this region abolished regulation [1].
• Phosphorylated BvgA is sufficient for transcriptional activation of virulence-regulated genes in Bordetella pertussis [8].
• We suggest that the previously observed differences in regulation of individual virulence-associated genes reflect differences in the phosphorylation state of BvgA [8].

Anatomical context of vrg-6

• These virulence factors include adhesins such as filamentous haemagglutinin, fimbriae and pertactin, which allow B. pertussis to bind to ciliated epithelial cells in the upper respiratory tract [15].
• Nonopsonized Bordetella pertussis bind to human monocytes by means of the virulence factors filamentous hemagglutinin (FHA), pertactin, and the minor fimbrial subunit FimD [16].
• These transporters are critical for the pathogenic process in that they export important virulence factors across the membranes of the bacteria [17].
• Bordetella pertussis virulence factors affect phagocytosis by human neutrophils [18].
• In this study, we investigated the ability of a virulent strain, avirulent mutants, and mutants deficient in specific virulence factors to enter and survive intracellularly in human macrophages in vitro [19].

Associations of vrg-6 with chemical compounds

• The strains which had at least one virulence trait also demonstrated some adenylate cyclase activity [20].
• The responses to glutamate depletion exhibited similarities to the responses induced by exit from log phase, including decreased virulence factor transcript levels [21].
• It was found that the leukocytosis-promoting, histamine-sensitizing, and mouse-protecting activities of the mutants were similar to those of the parent strain but that the virulence to mice was lower [22].
• From a bank of TnphoA fusions, we have identified five genes whose expression profiles are reciprocal of those of the major virulence determinants; that is, alkaline phosphatase activity is maximal during growth in the presence of the modulators nicotinic acid and MgSO4 (S. Knapp and J. J. Mekalanos, J. Bacteriol. 170:5059-5066, 1988) [1].
• Apart from iron regulation, sodA expression was affected by changes in DNA topology induced by coumermycin A but not by the global virulence regulatory Bvg system [23].

Other interactions of vrg-6

• Targeted mutations that ablate either the adenylate cyclase or hemolysin function of the bifunctional cyaA toxin of Bordetella pertussis abolish virulence [24].
• A mutation in the Bordetella bronchiseptica bvgS gene results in reduced virulence and increased resistance to starvation, and identifies a new class of Bvg-regulated antigens [25].
• Mutations in the bvgA gene of Bordetella pertussis that differentially affect regulation of virulence determinants [26].
• 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 [27].
• We have therefore used the RIVET system to reveal the time-course of gene expression in vivo for selected B. pertussis virulence factors (cya, fha, prn and ptx) [28].

Analytical, diagnostic and therapeutic context of vrg-6

• Using a Bordetella DNA microarray, we discovered significant changes in transcript abundance for 861 array elements during the transition from log phase to stationary phase, including declining transcript levels of many virulence factor genes [21].
• In the present study, we analyzed B. pertussis isolates collected in Japan from 1988 to 2001 using pulsed-field gel electrophoresis (PFGE) and sequencing of two virulence-associated proteins [29].
• A LightCycler real-time PCR hybridization probe assay was developed for rapid typing of gene variants of the Bordetella pertussis virulence factor pertussis toxin [30].
• Identification of Btr-regulated genes using a titration assay. Search for a role for this transcriptional regulator in the growth and virulence of Bordetella pertussis [31].
• Thorough understanding of the mechanism of action of the B. parapertussis virulence factors, such as FHA, is of particular interest in the development of novel strategies of pertussis vaccination [32].

References