Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis

Xu, Yinghua; Liu, Bin; Gröndahl-Yli-Hannuksila, Kirsi; Tan, Yajun; Feng, Lu; Kallonen, Teemu; Wang, Lichan; Ding, Peng; He, Qiushui; Wang, Lei; Zhang, Shumin

doi:10.1038/srep12888

Cited by 46 publications

(44 citation statements)

References 57 publications

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“…Yet B. pertussis persists, and pertussis disease has resurged, in part due to genetic divergence of circulating strains. Although reference strains used for vaccine production vary (1), growing evidence suggests that B. pertussis is evolving under vaccine-driven selection (2–5). Here, we report the complete genome sequences of four strains (134, 509, 6229, 25525) used by Serum Institute of India to manufacture whole-cell pertussis vaccines.…”

Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequences of Four Bordetella pertussis Vaccine Reference Strains from Serum Institute of India

et al. 2016

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Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequences of Four Bordetella pertussis Vaccine Reference Strains from Serum Institute of India

et al. 2016

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“…The global emergence of Prn deficiency is well documented (13,14) but, although likely vaccine driven (15), does not appear to impact the effectiveness of aP vaccines (16). Together, such genetic shifts illustrate how circulating B. pertussis has significantly diverged from vaccine reference strains since widespread vaccine introduction, which many researchers have attributed to vaccine-driven immune selection (4,10,15,(17)(18)(19)(20).…”

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confidence: 99%

Screening and Genomic Characterization of Filamentous Hemagglutinin-Deficient Bordetella pertussis

et al. 2018

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Despite high vaccine coverage, pertussis cases in the United States have increased over the last decade. Growing evidence suggests that disease resurgence results, in part, from genetic divergence of circulating strain populations away from vaccine references. The United States employs acellular vaccines exclusively, and current isolates are predominantly deficient in at least one immunogen, pertactin (Prn). First detected in the United States retrospectively in a 1994 isolate, the rapid spread of Prn deficiency is likely vaccine driven, raising concerns about whether other acellular vaccine immunogens experience similar pressures, as further antigenic changes could potentially threaten vaccine efficacy. We developed an electrochemiluminescent antibody capture assay to monitor the production of the acellular vaccine immunogen filamentous hemagglutinin (Fha). Screening 722 U.S. surveillance isolates collected from 2010 to 2016 identified two that were both Prn and Fha deficient. Three additional Fha-deficient laboratory strains were also identified from a historic collection of 65 isolates dating back to 1935. Whole-genome sequencing of deficient isolates revealed putative, underlying genetic changes. Only four isolates harbored mutations to known genes involved in Fha production, highlighting the complexity of its regulation. The chromosomes of two Fha-deficient isolates included unexpected structural variation that did not appear to influence Fha production. Furthermore, insertion sequence disruption of was also detected in a previously identified pertussis toxin-deficient isolate that still produced normal levels of Fha. These results demonstrate the genetic potential for additional vaccine immunogen deficiency and underscore the importance of continued surveillance of circulating evolution in response to vaccine pressure.

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“…Previous genomic studies have identified only a few mutations within a limited number of genes, each of which have quickly spread throughout the circulating population with little evidence of geographic restriction (5,11). These mutations have occurred in genes encoding immunogenic proteins, most notably those for antigens in currently used acellular pertussis vaccines, such as genes for pertussis toxin (ptxA and the promoter region ptxP) and fimbriae (fimH), leading many to conclude that they result from vaccine-driven selection (5,(12)(13)(14)(15). Although sequence diversity has also been observed in the vaccine immunogen pertactin (Prn), the circulating isolates recovered in the United States have become predominantly Prn deficient in recent years by one of at least 16 different mutations to the prn gene (16).…”

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The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

et al. 2017

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Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. Although Bordetella pertussis is well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genomic structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257 B. pertussis isolates to examine the potential evolution of the chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. The observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS481, a mobile genetic element with Ͼ240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution in B. pertussis is not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigating disease resurgence and molecular epidemiology.IMPORTANCE Whooping cough, primarily caused by Bordetella pertussis, has resurged in the United States even though the coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome of B. pertussis includes a large number of repetitive mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-encoding genes, which otherwise exhibit little nucleotide sequence diversity. By comparing the complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology.

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Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis

Cited by 46 publications

References 57 publications

Complete Genome Sequences of Four Bordetella pertussis Vaccine Reference Strains from Serum Institute of India

Complete Genome Sequences of Four Bordetella pertussis Vaccine Reference Strains from Serum Institute of India

Screening and Genomic Characterization of Filamentous Hemagglutinin-Deficient Bordetella pertussis

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

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