Bordetella Species Are Distinguished by Patterns of Substantial Gene Loss and Host Adaptation

Abstract

Pathogens of the bacterial genus Bordetella cause respiratory disease in humans and animals. Although virulence and host specificity vary across the genus, the genetic determinants of this diversity remain unidentified. To identify genes that may underlie key phenotypic differences between these species and clarify their evolutionary relationships, we performed a comparative analysis of genome content in 42 Bordetella strains by hybridization of genomic DNA to a microarray representing the genomes of three Bordetella species and by subtractive hybridization. Here we show that B. pertussis and B. parapertussis are predominantly differentiated from B. bronchiseptica by large, species-specific regions of difference, many of which encode or direct synthesis of surface structures, including lipopolysaccharide O antigen, which may be important determinants of host specificity. The species also exhibit sequence diversity at a number of surface protein-encoding loci, including the fimbrial major subunit gene, fim2. Gene loss, rather than gene acquisition, accompanied by the proliferation of transposons, has played a fundamental role in the evolution of the pathogenic bordetellae and may represent a conserved evolutionary mechanism among other groups of microbial pathogens.Bacteria of the genus Bordetella are important pathogens that cause respiratory disease in humans and animals. B. pertussis is the causative agent of whooping cough (8), which is responsible for up to 500,000 annual deaths worldwide in unvaccinated populations (52) and is increasing in incidence in some countries with established vaccination programs, including the United States (e.g., see references 15, 30, and 38). Although most Bordetella species can cause similar disease in the upper respiratory tract, their host specificities vary dramatically. B. pertussis infects only humans; B. parapertussis strains can be classified in two groups, one of which infects only humans and one of which infects only sheep (16,17,25); B. bronchiseptica causes respiratory infections in a wide variety of mammals and birds but only rarely in humans (22,41,51).These three Bordetella species are closely related at the nucleotide sequence level (4, 24), and their relatedness has been further established using a variety of common molecular strain typing techniques (reviewed in reference 29). Phylogenetic analyses of the genus Bordetella, using pulsed-field gel electrophoresis, multilocus enzyme electrophoresis (MLEE), and IS typing data, suggested that B. pertussis, human-derived B. parapertussis, and sheep-derived B. parapertussis arose independently from B. bronchiseptica-like ancestors (46, 47). Comparative genome sequencing of a representative strain of each species (33) confirmed that nucleotide sequence similarity is very high in conserved regions of the genome but demonstrated that B. pertussis and B. parapertussis evolved by genome decay from a B. bronchiseptica-like ancestor.Although a number of critical conserved virulence mechanisms have been identified in the bor...

A Novel Sensor Kinase Is Required for Bordetella bronchiseptica To Colonize the Lower Respiratory Tract

“…Bordetella bronchiseptica infects a wide range of mammals, while Bordetella pertussis and humanadapted Bordetella parapertussis, which presumably diverged from a B. bronchiseptica-like ancestor, are restricted to infecting humans and cause the disease known as whooping cough or pertussis (15,16,47,64). Despite widespread vaccine coverage, the number of whooping cough cases has increased in recent years (8,69), prompting the need for a better understanding of the mechanisms used by these pathogens to colonize the respiratory tract.…”

“…Somewhat surprising, then, is the fact that orthologues of a majority of these TCSs are found in the human-restricted strain B. pertussis. Since gene loss is hypothesized to be a mechanism by which B. pertussis restricted its host range to the human respiratory tract (15,47,52), it is reasonable to assume that regulatory systems providing no selective advantage in this niche would be lost as well. Our data suggest that, in B. bronchiseptica, a majority of TCSs are not required for colonization of the respiratory tract, at least in a rat natural infection model, as all mutant B. bronchiseptica strains tested in this study (except the plrS mutant) that harbor a single mutation in a predicted TCS were as efficient as the wild-type strain in colonizing the respiratory tract (Table 2 and data not shown).…”

Bordetellafilamentous hemagglutinin plays a critical role in immunomodulation, suggesting a mechanism for host specificity

“…The causative agents, Bordetella pertussis and Bordetella parapertussis hu , are human-adapted pathogens that belong to a clade of very closely related Gram-negative bacteria that cause respiratory infections in mammals. Phylogenetic analyses indicate that Bordetella bronchiseptica, which displays a broad host range and typically colonizes its hosts chronically and asymptomatically, was the progenitor of this clade, with B. pertussis diverging relatively early and B. parapertussis hu diverging independently and much more recently than B. pertussis (3)(4)(5)(6). Adaptation to humans and the propensity to cause acute disease (in which the infection is eventually cleared) rather than chronic disease (characterized by persistence of the bacteria, often for the lifetime of the host) has, therefore, evolved twice within this group of bacteria.…”

Examination of animal and zoonotic pathogens using microarrays

“…Although the three species are genetically closely related, differences for host specificity and pathogenicity exist. In order to examine the differences in virulence and host specificity, microarray based comparative genome hybridization coupled with suppressive subtractive hybridization was employed [29]. For this study, PCR amplified probes from the three bordetellae were spotted on a glass slide and hybridized with the genomic DNA of 42 Bordetella strains.…”