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Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis , and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape. Whooping cough is mainly caused by Bordetella pertussis , and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.

Pertussis (or whooping cough) has experienced a global resurgence despite widespread vaccine efforts. In China, the incidence of pertussis has rapidly increased, particularly following the COVID-19 pandemic. Whole-genome sequencing analysis was performed on 60 strains isolated in Beijing from 2020-2023, and the sequences were compared with those of 635 strains from China and 943 strains from other countries. In this study, the genetic evolution of was investigated, focusing on key virulence genes ( , , , , , ) and the resistance-related locus A2047 across different periods and regions. The dominant antigen genotype among the 60 isolates was / / / / / (88.3%), differing from the prevalent genotype in Beijing prior to 2019 and the vaccine strain genotype / / / / / . Evolutionary analysis revealed significant genetic shifts associated with the introduction of vaccines, particularly acellular vaccines. Initially, the prevalent genotypes included , , , , and . However, currently, , and have become predominant globally, indicating vaccine-induced selection pressure. Additionally, all 60 isolated strains (100%) presented the A2047G mutation associated with erythromycin resistance, of which accounted for 91.7%. Macrolide-resistant (MRBP) is widespread in China, and the prevalence of MRBP may be increasing. The significant changes of dominance of subtypes in Beijing in recent years underscore the need for continuous surveillance and adaptation of pertussis vaccination strategies.

Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 10³, 10⁵ or 10⁷ colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. ClinicalTrials.gov NCT01188512.

Background Pertussis, a highly contagious respiratory disease caused by Bordetella pertussis (BP), poses challenges due to genomic variation that may contribute to its persistence in vaccinated populations and the development of antimicrobial resistance. Methods In this study, we characterized 27 BP isolates collected from Tianjin, China in 2023, using whole-genome sequencing and multilocus genotyping (MGT) to explore their genomic diversity. For comparative analysis, we selected 165 international BP genomes to examine the genomic diversity and evolutionary traits of Tianjin strains within a global context. Results The results revealed that all 27 isolates belonged to ST2 (100.0%), with no distinct phylogenetic clustering observed. Furthermore, phylogenetic analysis integrating 165 global BP genomes indicated that the Tianjin strains exhibited high genomic homogeneity with globally circulating strains. Specifically, 16 isolates (59.3%) carried the virulence genotype ptxA-1/ptxC-4/ptxP-3/prn-150(truncated)/fim2-1/fim3-1/fhaB-1 , while 11 isolates (40.7%) carried the genotype ptxA-1/ptxC-4/ptxP-3/prn150/fim2-1/fim3-1/fhaB-1 . Additionally, all 27 isolates exhibited complete resistance to erythromycin, azithromycin, clarithromycin, and clindamycin, whereas 18.5% of them were resistant to levofloxacin. Conclusions This study elucidates the phylogenetic, genomic characteristics, and drug sensitivity profiles of BP strains isolated in Tianjin, China, in 2023, providing valuable insights into BP persistence in vaccinated populations.

Background. A recent increase in Bordetella pertusis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN−) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed. Methods. We retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis. Results. Among 753 isolates, 640 (85%) were PRN−. The age distribution differed between cases caused by PRN− B. pertussis and cases caused by B. pertussis producing pertactin (PRN+) (P = .01). The proportion reporting individual pertussis symptoms was similar between the 2 groups, except a higher proportion of PRN+ case-patients reported apnea (P = .005). Twenty-two case-patients were hospitalized; 6% in the PRN+ group compared to 3% in the PRN− group (P = .11). Case-patients having received at least 1 pertussis vaccine dose had a higher odds of having PRN− B. pertussis compared with unvaccinated case-patients (adjusted OR = 2.2; 95% confidence interval [CI], 1.3–4.0). When restricted to case-patients at least 1 year of age and those age-appropriately vaccinated, the adjusted OR increased to 2.7 (95% CI, 1.2–6.1). Conclusions. The significant association between vaccination and isolate pertactin production suggests that the likelihood of having reported disease caused by PRN− compared with PRN+ strains is greater in vaccinated persons. Additional studies are needed to assess whether vaccine effectiveness is diminished against PRN− strains.

The respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica exhibit cytotoxicity toward a variety of mammalian cells, which depends on the type III secretion effector BteA. Moreover, the increased virulence of B. bronchiseptica is associated with enhanced expression of T3SS and BteA. However, the molecular mechanism underlying BteA cytotoxicity is elusive. In this study, we performed a CRISPR-Cas9 screen, revealing that BteA-induced cell death depends on essential or redundant host processes. Additionally, we demonstrate that BteA disrupts calcium homeostasis, which leads to mitochondrial dysfunction and cell death. These findings contribute to closing the gap in our understanding of the signaling cascades targeted by BteA.

Background. During 9 May 2010–7 May 2011, an outbreak of pertussis-like illness (incidence, 80 cases per 100 000 persons) occurred in Franklin County, Ohio. The majority of cases were identified by IS481-directed polymerase chain reaction (PCR), which does not differentiate among Bordetella species. We sought to determine outbreak etiology and epidemiologic characteristics. Methods. We obtained demographic, clinical, and vaccination-related data from the Ohio Disease Reporting System and Impact Statewide Immunization Information System. We tested sera from 14 patients for anti—pertussis toxin (PT) antibodies and used species-specific PCR on 298 nasopharyngeal specimens. Results. Reported cases totaled 918. IS481 results were available for 10 serologically tested patients; 5 of 10 had discordant anti-PT antibody and IS481 results, suggestive of Bordetella holmesii, which lacks PT and harbors IS481. We identified specific Bordetella species in 164 of 298 specimens tested with multitarget PCR; B. holmesii and Bordetella pertussis were exclusively detected among 48 (29%) and 112 (68%), respectively; both were detected in 4 (2%). Among 48 patients with B. holmesii infections, 63% were aged 11–18 years, compared with 35% of 112 patients with B. pertussis infections (P = .001). Symptoms were similar among B. holmesii—and B. pertussis—infected patients. Adolescent pertussis (\"Tdap\") booster vaccinations were more effective against B. pertussis than B. holmesii (effectiveness: 67% and 36%, respectively; 95% confidence intervals, 38%–82% and −33% to 69%, respectively). Conclusions. We report the first documented mixed outbreak of B. pertussis and B. holmesii infections. Bordetella holmesii particularly affected adolescents. Although laboratory capacity limitations might inhibit routine use of multitarget PCR for clinical diagnosis, focused testing and enchanced surveillance might improve understanding the burden of B. holmesii infection.

Pertussis, caused by Bordetella pertussis , remains a significant public health concern despite widespread vaccination. Recent increases in macrolide-resistant strains present additional challenges for treatment and control. Yiwu, China—a highly mobile and international city—offers a unique setting to study the genomic evolution and antimicrobial resistance of B. pertussis . In this study, 63 clinical isolates from Yiwu underwent whole-genome sequencing. Over 90% of isolates showed high resistance to macrolides. Genome sizes ranged from 3.53 to 4.15 Mb, with high GC content (67.69–67.80%) and variable repeat rates. Phylogenetic analysis, incorporating 14 international strains, revealed two distinct clades and lineage-specific variations in key vaccine antigen genes, indicating multiple origins and localized evolution. A comparative analysis between resistant and sensitive isolates identified an A2037G substitution in the 23S rRNA gene strongly associated with macrolide resistance. Additionally, 69 highly divergent genes related to transcriptional regulation, recombination, and membrane function were detected. Notably, two outer membrane efflux protein genes, opm D and opr M, showed nonsynonymous mutations potentially linked to resistance enhancement. The presence of genomic islands, prophages, and antigenic gene variation further underscores the dynamic evolution of B. pertussis in the region. This study highlights the urgent need for alternative therapies and improved vaccines, while also demonstrating the value of continued genomic surveillance. Insights into resistance-associated genes offer new targets for functional studies and may guide future strategies in pertussis control.

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.

Various strains emerged in re-emergence, the pathogenic characteristics and mechanisms remain elusive. We aimed to explore the relationship between the transcriptome and colonization advantage of various pertussis clinical strains during the re-emergence. Four pertussis strains were isolated from clinically suspected cases by active surveillance. The phylogenetic relationships of clinical strains and global isolates were compared by a genome-wide SNP-based phylogenetic tree and allele genotyping. LC-MS/MS analysis and binding affinity detection allowed the identification of expression and antigenicity of pertactin. The characteristics of infection and immunity of clinical strains were compared in a BALB/c mouse aerosol challenge model. RNA-seq analysis was performed in NSG mouse model to describe the transcriptome during infection, and verified by detecting biofilm formation and paraquat tolerance. The partial pertactin-deficient strain BP-L2 was first reported. It showed significantly enhanced tracheal colonization compared to both CS and BP-L1 strains in naive mice ( < 0.0001 . CS) and exhibited superior fitness over BP-L1 in immunized mice ( < 0.001). BP-L1 showed superior lung colonization ( < 0.0001) and tissue-resident memory T cell induction versus BP-L2 and CS ( < 0.001). Colonization dominance of BP-L1 in lungs and BP-L2 in trachea aligned with the pathological injury ( < 0.05) and the inflammatory cytokine enhancement (IL-6 in lungs of BP-L1 group, < 0.01). RNA-seq results revealed that BP-L2 significantly upregulated (log2FC = 2.1, = 0.019) and (log2FC =2.4, = 8.61E-06) compared to BP-L1, functionally linked to enhanced stringent response and oxidative stress defense. BP-L1 exhibited significant upregulation over BP-L2 (log2FC = 1.8, = 0.027) without concurrent biofilm enhancement ( = 0.51 . BP-L2). Furthermore, the BP-L2 and BP-L3 strains of the same lineage showed significantly higher paraquat tolerance than other strains ( < 0.001), showing extremely high SODs activity. The emerging pertussis strains exhibit different colonization advantages in the trachea or lungs, which will influence the transmission patterns of the clinical strains. The tracheal colonization advantage of the partial pertactin-deficient strain may be associated with the overexpression of the and infection.