The virulence factors of Bordetella pertussis: A matter of control

Department of Biological Sciences, University of Wollongong, Wollongong. N.S.W. 2522, Australia.
FEMS Microbiology Reviews (Impact Factor: 13.24). 06/2001; 25(3):309-33. DOI: 10.1016/S0168-6445(01)00056-0
Source: PubMed


Bordetella pertussis is the causative agent of whooping cough, a contagious childhood respiratory disease. Increasing public concern over the safety of whole-cell vaccines led to decreased immunisation rates and a subsequent increase in the incidence of the disease. Research into the development of safer, more efficacious, less reactogenic vaccine preparations was concentrated on the production and purification of detoxified B. pertussis virulence factors. 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. Once attachment is initiated, toxins produced by the bacterium enable colonisation to proceed by interfering with host clearance mechanisms. B. pertussis co-ordinately regulates the expression of virulence factors via the Bordetella virulence gene (bvg) locus, which encodes a response regulator responsible for signal-mediated activation and repression. This strict regulation mechanism allows the bacterium to express different gene subsets in different environmental niches within the host, according to the stage of disease progression.

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Available from: Mark J Walker, Oct 13, 2014
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    • "To examine the possible basis for differences in virulence phenotypes amongst strains/lineages, we compared the presence/absence of factors thought to be involved in interactions with the host, loosely referred to as “virulence factors”, including filamentous hemagglutinin (FHA), fimbriae (Fims), pertactin (PRN), tracheal colonization factor (TcfA), adenylate cyclase/hemolysin (ACT), dermonecrotic toxin (Dnt), pertussis toxin (Ptx), Bordetella resistance to killing (BrkA) protein [29], O-antigen [30], Type III secretion system (TTSS) [31], and Type VI secretion system (T6SS) [32]. Only genes encoding FHA, PRN, and TTSS locus are conserved in all strains (Figure 4). "
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    ABSTRACT: Background The classical Bordetella subspecies are phylogenetically closely related, yet differ in some of the most interesting and important characteristics of pathogens, such as host range, virulence and persistence. The compelling picture from previous comparisons of the three sequenced genomes was of genome degradation, with substantial loss of genome content (up to 24%) associated with adaptation to humans. Results For a more comprehensive picture of lineage evolution, we employed comparative genomic and phylogenomic analyses using seven additional diverse, newly sequenced Bordetella isolates. Genome-wide single nucleotide polymorphism (SNP) analysis supports a reevaluation of the phylogenetic relationships between the classical Bordetella subspecies, and suggests a closer link between ovine and human B. parapertussis lineages than has been previously proposed. Comparative analyses of genome content revealed that only 50% of the pan-genome is conserved in all strains, reflecting substantial diversity of genome content in these closely related pathogens that may relate to their different host ranges, virulence and persistence characteristics. Strikingly, these analyses suggest possible horizontal gene transfer (HGT) events in multiple loci encoding virulence factors, including O-antigen and pertussis toxin (Ptx). Segments of the pertussis toxin locus (ptx) and its secretion system locus (ptl) appear to have been acquired by the classical Bordetella subspecies and are divergent in different lineages, suggesting functional divergence in the classical Bordetellae. Conclusions Together, these observations, especially in key virulence factors, reveal that multiple mechanisms, such as point mutations, gain or loss of genes, as well as HGTs, contribute to the substantial phenotypic diversity of these versatile subspecies in various hosts.
    BMC Genomics 10/2012; 13(1):545. DOI:10.1186/1471-2164-13-545 · 3.99 Impact Factor
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    • "Xanthomonadaceae encode type V-secreted proteins which could act as nonfimbrial adhesins (Table 5.1) (Moreira et al., 2004; Van Sluys et al., 2002). These proteins are related to the prototypic yersinial adhesins YadA and YapH and to wellstudied adhesins from Bordetella pertussis (pertactin, filamentous hemagglutinin FHA) and Haemophilus influenzae (HMW1, HMW2) (Hoiczyk et al., 2000; Smith et al., 2001; St Geme 3rd and Yeo, 2009). Comparative genomics revealed that predicted adhesion genes of some strains have frameshift mutations and/or in-frame stop codons, thus most likely leading to truncated, probably inactive protein variants (Table 5.1) (Bhattacharyya et al., 2002; Van Sluys et al., 2003). "
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    ABSTRACT: The family Xanthomonadaceae is a wide-spread family of bacteria belonging to the gamma subdivision of the Gram-negative proteobacteria, including the two plant-pathogenic genera Xanthomonas and Xylella, and the related genus Stenotrophomonas. Adhesion is a widely conserved virulence mechanism among Gram-negative bacteria, no matter whether they are human, animal or plant pathogens, since attachment to the host tissue is one of the key early steps of the bacterial infection process. Bacterial attachment to surfaces is mediated by surface structures that are anchored in the bacterial outer membrane and cover a broad group of fimbrial and non-fimbrial structures, commonly known as adhesins. In this chapter, we discuss recent findings on candidate adhesins of plant-pathogenic Xanthomonadaceae, including polysaccharidic (lipopolysaccharides, exopolysaccharides) and proteineous structures (chaperone/usher pili, type IV pili, autotransporters, two-partner-secreted and other outer membrane adhesins), their involvement in the formation of biofilms and their mode of regulation via quorum sensing. We then compare the arsenals of adhesins among different Xanthomonas strains and evaluate their mode of selection. Finally, we summarize the sparse knowledge on specific adhesin receptors in plants and the possible role of RGD motifs in binding to integrin-like plant molecules.
    Advances in Experimental Medicine and Biology 01/2011; 715:71-89. DOI:10.1007/978-94-007-0940-9_5 · 1.96 Impact Factor
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    • "It has been hypothesized (Cummings et al., 2006; Nakamura et al., 2006) that the virulence state of members of the Bordetella genus is associated with survival outside the host and adaptation to unfavorable conditions on one hand and colonization and infection of the host on the other hand. B. pertussis can switch between these states (Cotter and Jones, 2003; Scarlato et al., 1990; Smith et al., 2001), which each have specific proteins that are involved in the mechanisms necessary either for survival or colonization. The proteins involved in colonization and infection (so-called virulence factors) are the targets against which a protective immune response is raised in a whole cell vaccine against whooping cough. "
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    ABSTRACT: Modern (bio)pharmaceutical process development requires thorough investigation of all process parameters that are critical to product quality. The impact of a disturbance of such a parameter during processing needs to be known so that a rational decision can be made about the release of the product. In cultivation processes the dissolved oxygen (DO) concentration is generally accepted as being a critical parameter. In this article the impact of a 90 min period of oxygen limitation during the cultivation of the strictly aerobic Bordetella pertussis bacterium is investigated. The cultivation is the most important process step for the manufacturing of a vaccine against whooping cough disease. Samples were taken immediately before and after oxygen limitation and at the end of cultivation of four oxygen limited and three control cultivations. DNA microarray analysis of the full transcriptome of the B. pertussis bacterium revealed that a 90 min period of oxygen limitation has a substantial effect on overall gene expression patterns. In total 104 genes were identified as a significant hit at any of the sample points, of which 58 were directly related to oxygen limitation. The other genes were mainly affected towards the end of cultivation. Of all genes involved in oxygen limitation none were identified to show a significant difference between the oxygen limited and control cultivations at the end of the batch. This indicates a fully reversible effect of oxygen limitation on gene expression. This finding has implications for the risk assessment of dissolved oxygen concentration as a critical process parameter.
    Biotechnology and Bioengineering 01/2009; 102(1):161-7. DOI:10.1002/bit.22030 · 4.13 Impact Factor
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