<i>Bordetella pertussis</i>Strains with Increased Toxin Production Associated with Pertussis Resurgence

Mooi, Frits R.; Loo, Inge H. M. van; Gent, Marjolein van; He, Qiushui; Bart, Marieke J.; Heuvelman, Kees; Greeff, Sabine C. de; Diavatopoulos, Dimitri A.; Teunis, Peter; Nagelkerke, Nico; Mertsola, Jussi

doi:10.3201/eid1508.081511

Cited by 295 publications

(368 citation statements)

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“…Although the ptxP3 allele is thought to increase pertussis toxin expression (40,41), a recent comparison of isogenic mutants found that the ptxP3 allele and the genetic background, which includes genomic structure, independently enhance colonization in mice (42). Similarly, although alleles of fimH contain polymorphisms in the predicted surface epitope region, differences in immune recognition remain untested (43).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

et al. 2017

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“…In addition to conventional resistance mechanisms (e.g., efflux pumps to thwart drugs or antigenic variation to escape vaccine‐induced immunity), experiments have shown that parasite virulence can evolve in response to—and mitigate the effects of—medical interventions, as exemplified by Marek's disease virus in response to vaccines (Read et al., 2015), and rodent malaria parasites in response to drugs (Schneider et al., 2012) and vaccines (Barclay et al., 2012). The extent of this kind of evolution in nonexperimental systems is poorly understood, but there is some evidence of vaccine‐driven virulence evolution in parasites of humans (pertussis, Mooi et al., 2009), cats (feline calicivirus, Radford, Dawson, Coyne, Porter, & Gaskell, 2006) and poultry (Marek's disease virus, Nair, 2005; avian infectious bursal disease virus, van den Berg, 2000). Through the development of general theory, Gandon, Mackinnon, Nee, and Read (2001) formalized the prediction that imperfectly effective, or “leaky” vaccines can drive virulence evolution.…”

Section: Introductionmentioning

confidence: 99%

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Mideo

2017

Evolutionary Applications

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Average HIV‐1 virulence appears to have evolved in different directions in different host populations since antiretroviral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virulence evolution in response to “leaky” therapy (treatment that imperfectly suppresses viral replication) and the use of preventive drugs (pre‐exposure prophylaxis) has not been explored. Using adaptive dynamics, we show that higher virulence can evolve when antiretroviral therapy is imperfectly effective and that this evolution erodes some of the long‐term clinical and epidemiological benefits of HIV treatment. The introduction of pre‐exposure prophylaxis greatly reduces infection prevalence, but can further amplify virulence evolution when it, too, is leaky. Increasing the uptake rate of these imperfect interventions increases selection for higher virulence and can lead to counterintuitive increases in infection prevalence in some scenarios. Although populations almost always fare better with access to interventions than without, untreated individuals could experience particularly poor clinical outcomes when virulence evolves. These findings predict that antiretroviral drugs may have underappreciated evolutionary consequences, but that maximizing drug efficacy can prevent this evolutionary response. We suggest that HIV virulence evolution should be closely monitored as access to interventions continues to improve.

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“…For ptxP sequence-based typing, the promoter region was amplified using primers and conditions based on those previously described (Mooi et al, 2009;and M. van Gent, personal communication). Each 20 ml PCR contained 10 ml HotStarTaq Master Mix (Qiagen), 1 mM each primer, 1 M betaine (Sigma) and 2 ml DNA extract (for both bacterial isolates and clinical samples).…”

Section: Methodsmentioning

confidence: 99%

“…Characterizing changes in genes encoding known vaccine antigens or virulence factors such as the S1 and S3 subunits of pertussis toxin (ptxA and ptxC), pertactin (prn), tracheal colonization factor (tcfA) and fimbrial antigens 2 and 3 (fim2 and fim3) is also valuable (Mooi et al, 2007;Packard et al, 2004;Tsang et al, 2004;van Loo et al, 2002). Polymorphisms in the pertussis toxin promoter (ptxP) have also been proposed to affect the virulence of B. pertussis through increased Ptx production (Mooi et al, 2009;Mooi, 2010), although an increase in virulence was not seen in a recent study using a murine model of infection (Hegerle et al, 2012). Other methods designed to distinguish isolates, which are not linked to virulence factors, include PFGE, multilocus variablenumber tandem repeat analysis (MLVA) and genome-wide single nucleotide polymorphism (SNP) analysis (Mooi et al, 2000;Octavia et al, 2011;Schouls et al, 2004;van Gent et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Direct molecular typing of Bordetella pertussis from clinical specimens submitted for diagnostic quantitative (real-time) PCR

Litt¹,

Jauneikaite²,

Tchipeva

et al. 2012

Journal of Medical Microbiology

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Molecular typing of Bordetella pertussis is routinely performed on bacterial isolates, but not on DNA extracted from nasopharyngeal aspirates or pernasal swabs submitted for diagnostic realtime PCR (qPCR). We investigated whether these DNA extracts were suitable for multilocus variable-number tandem repeat analysis (MLVA) and DNA sequence-based typing. We analysed all the available qPCR-positive samples received by our laboratory from patients ,1 year of age between January 2008 and August 2010. Eighty-one per cent (106/131) of these generated a complete MLVA profile. This rose to 92 % (105/114) if only samples positive for both of the two targets used for the B. pertussis PCR (insertion element IS481 and pertussis toxin promoter ptxP) were analysed. Sequence-based typing of the pertactin, pertussis toxin S1 subunit and pertussis promoter regions (prn, ptxA and ptxP) was attempted on 89 of the DNA extracts that had generated a full MLVA profile. Eighty-three (93 %) of these produced complete sequences for all three targets. Comparison of molecular typing data from the 89 extracts with those from 111 contemporary bacterial isolates showed that the two sources yielded the same picture of the B. pertussis population [dominated by the MLVA-27 prn(2) ptxA(1) ptxP(3) clonal type]. There was no significant difference in MLVA type distribution or diversity between the two sample sets. This suggests that clinical extracts can be used in place of, or to complement, bacterial cultures for typing purposes (at least, in this age group). With small modifications to methodology, generating MLVA and sequence-based typing data from qPCR-positive clinical DNA extracts is likely to generate a complete dataset in the majority of samples from the ,1 year age group. Its success with samples from older subjects remains to be seen. However, our data suggest that it is suitable for inclusion in molecular epidemiological studies of the B. pertussis population or as a tool in outbreak investigations. INTRODUCTIONThe bacterium Bordetella pertussis causes potentially fatal pertussis disease in humans. Despite vaccination programmes that are highly effective in reducing serious disease and mortality, there has been some concern in developed countries that pertussis disease is on the increase. Various explanations have been proposed, including increased ascertainment due to improved diagnostic methods, poor efficacy of particular batches of vaccine, and genetic variation occurring in the bacterial population (Campbell et al., 2012;Celentano et al., 2005;Mooi et al., 1999;Mooi, 2010;Ntezayabo et al., 2003;Poynten et al., 2004; Tanaka et al., 2003). Protein sequence variation has been observed in many B. pertussis virulence factors, including components of acellular pertussis vaccines such as pertussis toxin (Ptx), pertactin (Prn) and fimbriae (Fim) (Mooi et al., 2007;Mooi, 2010). Experiments using animal models have shown that divergent Ptx, Prn and Fim types can result in immune evasion (Robinson et al., 1989;King et al. 2001;Gzyl et al., 20...

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Bordetella pertussisStrains with Increased Toxin Production Associated with Pertussis Resurgence

Abstract: A more virulent strain of the disease is emerging.

Cited by 295 publications

References 36 publications

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Direct molecular typing of Bordetella pertussis from clinical specimens submitted for diagnostic quantitative (real-time) PCR

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