Comparative genomics of the classical Bordetella subspecies: the evolution and exchange of virulence-associated diversity amongst closely related pathogens

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.

Novel, host-restricted genotypes of Bordetella bronchiseptica associated with phocine respiratory tract isolates

“…However, additional isolates from the Caspian Sea should be evaluated to better determine the extent of heterogeneity within the population. The pertactin repeat region DNA sequence representing allele 1-4a2/2-6a1, found in all Atlantic and North Sea seal lung isolates, has otherwise been reported in 22 B. bronchiseptica isolates from pigs (Register, 2004;Okada et al, 2014) and a South American monkey isolate, 1289 (Park et al, 2012). Neither the region 1 nor the region 2 sequences have been identified in any other species of Bordetella.…”

“…A tree based on genome-wide SNPs was constructed as described by Park et al (2012). Briefly, genome assemblies of B. bronchiseptica 253 (GenBank ID: HE965806.1), B. bronchiseptica MO149 (also known as D444, GenBank ID: HE965807.1), B. bronchiseptica 1289 (GenBank ID: HE983626.1), B. bronchiseptica MO211 (also known as D445, GenBank ID: HE983627.1), B. bronchiseptica R77 (also known as Bbr77 and MBORD675, GenBank: HE983628.1), M435/02/3 and M85/00/2 were each processed into 54 bp DNA reads and subsequently mapped against the genome sequence of the B. bronchiseptica reference strain RB50 (GenBank ID: BX470250.1), using SSAHA2 version 2.5.4 (Ning et al, 2001).…”

Comparative Analyses of a Cystic Fibrosis Isolate of Bordetella bronchiseptica Reveal Differences in Important Pathogenic Phenotypes

“…Given that T44625 is an ST27 strain, we reasoned that it shares significant sequence similarity with other ST27 strains. Using the RB50 genome sequence (7) as a reference for comparison, the sequenced genome of strain 253 (17), another ST27 strain, was examined for the presence of bipA. No gene or open reading frame corresponding to the RB50 bipA sequence could be identified in strain 253 (data not shown).…”

“…These included fimbrial serotype 2 (fim2), 3 O-antigenrelated genes (wbmS, wbmR, and wbmO), and bipA. PCR, Western blotting, and sequencing analysis further confirmed that T44625 expresses the alternative O antigen or O2 serotype and harbors a replacement of the cya operon with the ptp gene, and they demonstrated that the fim2 gene is present in T44625 but contains low sequence identity to fim2 from RB50 (17).…”

“…Since B. bronchiseptica is more genetically and clinically diverse than the other classical bordetellae, it was hypothesized that strains from different phylogenetic lineages of B. bronchiseptica utilize different sets of virulence factors (5,8,(12)(13)(14). Several studies have recently confirmed this hypothesis (15)(16)(17).…”