Acquisition and loss of virulence-associated factors during genome evolution and speciation in three clades of Bordetella species.

Bodo Linz,Liliana Losada,Norman K Fry,Lauren Brinkac,Yury V Ivanov,Simon R Harris,Eric T Harvill,Julian Parkhill,Andrew R Gorringe,Laura L Goodfield,Maria Kim,Karen B Register,Tracy L Nicholson,Andrew Preston

doi:10.1186/s12864-016-3112-5

Abstract

BackgroundThe genus Bordetella consists of nine species that include important respiratory pathogens such as the ‘classical’ species B. bronchiseptica, B. pertussis and B. parapertussis and six more distantly related and less extensively studied species. Here we analyze sequence diversity and gene content of 128 genome sequences from all nine species with focus on the evolution of virulence-associated factors.ResultsBoth genome-wide sequence-based and gene content-based phylogenetic trees divide the genus into three species clades. The phylogenies are congruent between species suggesting genus-wide co-evolution of sequence diversity and gene content, but less correlated within species, mainly because of strain-specific presence of many different prophages. We compared the genomes with focus on virulence-associated genes and identified multiple clade-specific, species-specific and strain-specific events of gene acquisition and gene loss, including genes encoding O-antigens, protein secretion systems and bacterial toxins. Gene loss was more frequent than gene gain throughout the evolution, and loss of hundreds of genes was associated with the origin of several species, including the recently evolved human-restricted B. pertussis and B. holmesii, B. parapertussis and the avian pathogen B. avium.ConclusionsAcquisition and loss of multiple genes drive the evolution and speciation in the genus Bordetella, including large scale gene loss associated with the origin of several species. Recent loss and functional inactivation of genes, including those encoding pertussis vaccine components and bacterial toxins, in individual strains emphasize ongoing evolution.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3112-5) contains supplementary material, which is available to authorized users.

Highlights

The genus Bordetella consists of nine species that include important respiratory pathogens such as the ‘classical’ species B. bronchiseptica, B. pertussis and B. parapertussis and six more distantly related and less extensively studied species
Based on phylogenetic trees created from a genome-wide sequence comparison and a gene content analysis, we show that the bordetellae evolved into three distinct clades of species that consist of: clade A) the three classical bordetellae B. bronchiseptica, B. pertussis and B. parapertussis, clade B) the non-classical species B. avium, B. hinzii, B. holmesii and B. trematum, and clade C) the opportunistic pathogens B. petrii and B. ansorpii
Initial comparisons of 16S rRNA sequences suggested that B. holmesii is more closely related to B. pertussis than it is to B. avium or B. trematum [28, 61], but subsequent analyses showed that B. holmesii likely acquired the 16S rRNA gene, part of the 23S rRNA gene and IS481 by horizontal gene transfer (HGT) from B. pertussis as comparative genomic hybridization showed substantial genomic divergence between the two species [57]

Summary

Introduction

The genus Bordetella consists of nine species that include important respiratory pathogens such as the ‘classical’ species B. bronchiseptica, B. pertussis and B. parapertussis and six more distantly related and less extensively studied species. Multi-locus Sequence Typing (MLST) of the genus Bordetella, supported by targeted genome sequencing revealed that B. pertussis and B. parapertussis independently. Despite differences in host range and disease, the classical bordetellae are very closely related and share many important virulence factors, including putative adhesins such as pertactin (PRN), filamentous hemagglutinin (FHA) and fimbriae, and toxins such as adenylate cyclase toxin (ACT), pertussis toxin (PT) and dermonecrotic toxin (DNT) [5]. Some virulenceassociated factors are species-specific such as a recently identified type-VI secretion system (T6SS) in B. bronchiseptica [8] which is missing in B. pertussis and probably not functional in B. parapertussis due to missing subsets of genes and/or pseudogenes within this locus [7]. Recent analysis of clinical B. holmesii genome sequences suggest that these strains are similar to B. pertussis in that all B. holmesii isolates belong to the same multilocus sequence type [14], these clinical strains lack the important virulence genes that are encoded by B. pertussis [14, 15]

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