Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Pawloski, Lucia; Queenan, Anne Marie; Cassiday, Pamela K.; Lynch, Alisson; Harrison, M. J.; Shang, Wenchi; Williams, Margaret M.; Bowden, Katherine E.; Burgos-Rivera, Brunilís; Qin, Xuan; Messonnier, Nancy E.; Tondella, M. Lucia

doi:10.1128/cvi.00717-13

Cited by 181 publications

(174 citation statements)

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“…The phylogeny of the genomes analyzed was reconstructed while excluding the nucleotide sequence of the highly variable gene prn, which encodes an immunogenic protein found in most current acellular vaccine formulations. Clinical isolates recovered in the United States have become increasingly Prn deficient in recent years by a variety of mutations to prn, including missense substitutions, insertions, deletions, and promoter disruption, but most frequently through IS481 insertion at one of three positions (16). Most mutations appeared to be restricted within the phylogeny of genomes here, with the exception of the IS481 insertions, even when closely related strains differed in genomic structure (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…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). The global emergence of Prn deficiency is well documented (16)(17)(18)(19), and deficiency may confer a fitness advantage during infection (20,21).…”

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confidence: 99%

“…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). The global emergence of Prn deficiency is well documented (16)(17)(18)(19), and deficiency may confer a fitness advantage during infection (20,21). While Prn deficiency appears to be more prevalent in isolates recovered from fully vaccinated patients, it does not appear to impact the effectiveness of acellular pertussis vaccines (22,23).…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 97%

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confidence: 99%

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confidence: 99%

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The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

et al. 2017

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“…Interactions between PRN and AC-Hly have only been hypothesized so far (Khelef & Guiso, 1995), but could draw attention in a background of an increasing prevalence of natural PRN-deficient isolates in countries vaccinating with APVs (Barkoff et al, 2012;Miyaji et al, 2013;Otsuka et al, 2012;Pawloski et al, 2014;Queenan et al, 2013;Quinlan et al, 2013). The loss of this adhesin does not impact the virulence or transmission of the bacterium (Bodilis & Guiso, 2013) and, despite the effectiveness of current APVs in preventing severe pertussis in children less than 6 months of age (Bodilis & Guiso, 2013), great concerns have arisen regarding the duration of APV-induced immunity if the prevalence of PRN-deficient isolates increases.…”

Section: Introductionmentioning

confidence: 99%

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Hégerlé

Guiso

2014

Microbiology

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Whooping cough is a vaccine-preventable disease presenting with epidemic cycles linked to natural and/or vaccine-driven evolution of the aetiological agent of the disease, Bordetella pertussis. Adenylate cyclase-haemolysin (AC-Hly) is a major toxin produced by this pathogen, which mediates macrophage apoptosis in vitro and in vivo. While current acellular pertussis vaccine (APV) formulations do not include AC-Hly, they all contain pertussis toxin and can comprise filamentous haemagglutinin (FHA), which interacts with AC-Hly, and pertactin (PRN), which has been hypothesized also to interact with AC-Hly. We aimed to study the capacity of specific antibodies to inhibit the in vitro B. pertussis AC-Hly-mediated cytotoxicity of J774A.1 murine macrophages in a background of a changing bacterial population. We demonstrate that: (i) clinical isolates of different types or PRN phenotype are all cytotoxic and lethal in the mouse model of respiratory infection; (ii) lack of PRN production does not impact AC-Hly-related phenotypes; (iii) anti-AC-Hly antibodies inhibit cell lysis whatever the phenotype of the isolate, while anti-PRN antibodies significantly inhibit cell lysis provided the isolate produces this antigen, which might be relevant in vivo for APV-induced immunity; and (iv) anti-FHA antibodies only inhibit lysis induced by isolates collected in 2012, maybe indicating specific characteristics of epidemic lineages of B. pertussis.

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“…Several studies have suggested reasons for the resurgence of pertussis in the United States, including waning immunity from the acellular pertussis vaccine that replaced whole cell vaccine (9)(10)(11)(12)(13)(14)(15)(16)(17)(18); medical advancements that have allowed more effective diagnosis and reporting of pertussis cases (19,20); asymptomatic transmission of B. pertussis from individuals vaccinated with the acellular pertussis vaccine (21,22); evolving variant strains of B. pertussis circulating that are less protected by the vaccine (23)(24)(25); and a decrease in vaccine coverage that has compromised herd/community immunity (1,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). It is clear that the rise in reported pertussis cases in the United States is a multifaceted problem not fully captured in national or state-level data.…”

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confidence: 99%

Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States

Aloe

Kulldorff

Bloom

2017

Proc. Natl. Acad. Sci. U.S.A.

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Because of increased numbers of recorded pertussis cases in the United States, this study sought to understand the role of nonmedical vaccine exemptions and waning immunity may have had on the resurgence of pertussis in the United States at the community level. We used geospatial scan statistics, SaTScan, version 9.4, to analyze nonmedical vaccine exemptions of children entering kindergarten in 2011 and 2012 and reported pertussis cases in 2012 for children in age groups 5 years and younger and 10 to 14 years. Eight statistically significant clusters of nonmedical vaccine exemptions in kindergarteners and 11 statistically significant clusters of pertussis cases in children and adolescents were identified and geospatially linked. Forty-five percent of the counties in the study had high rates of nonmedical vaccine exemptions. The proportion of kindergarteners with nonmedical vaccine exemptions was 2.8 times larger in the identified exemption clusters. In addition, 31 counties had geographic clusters of high rates of pertussis in children ages 10 to 14 years old, consistent with waning immunity. Our findings are consistent with the view that geographic clusters of nonmedical vaccine exemptions and waning immunity may have been factors contributing to community-level pertussis outbreaks.

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Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Cited by 181 publications

References 29 publications

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

Antibody-mediated inhibition of Bordetella pertussis adenylate cyclase–haemolysin-induced macrophage cytotoxicity is influenced by variations in the bacterial population

Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States

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