Comparative genomics of whole-cell pertussis vaccine strains from India

- Comparative genomics of whole-cell pertussis vaccine strains from India.
- Genetic divergence in circulating strains of Bordetella pertussis has been reported as one of the contributing factors for the resurgence of the disease.
- We report here comparative genome analyses of vaccine and clinical isolates reported from India.
- Whole-genome sequences obtained from vaccine strains: WCV (J445, J446, J447 and J448), ACV (BP165) were compared with Tohama-I reference strain and recently reported clinical isolates from India (BPD1, BPD2).
- Results: Whole-genome analysis of vaccine and clinical isolates reported from India revealed high genetic similarity and conserved genome among strains.
- Phylogenetic analysis showed that clinical and vaccine strains share genetic closeness with reference strain Tohama-I.
- The allelic profile of vaccine strains (J445: ptxP1/ptxA2/prn1/fim2–1/fim3–1 .
- which matched entirely with clinical isolates (BPD1: ptxP1/ptxA1/prn1/fim2–1 and BPD2: ptxP1/ptxA1/prn1/fim2–1 ) reported from India.
- Keywords: Bordetella pertussis , Whooping cough, Resurgence, Antigenic variation, Genome organization, Virulence genes, Vaccine-mediated selection.
- Genome sequences of two In- dian clinical isolates BPD1 (CP034102) and BPD2 (CP034101) are reported.
- We report here comparative genomic analysis of five vaccine strain and two clinical isolates from India with the reference strain.
- The pseudogenes were also studied in vaccine and clinical isolates as compared to Tohama-I (Table 1).
- Vaccine strains and clinical isolates displayed more than 95% similarity with Tohama-I (Table 2).
- To estimate a general functional role of the CDS present in the average genome of eight strains used in this study, the clusters of orthologous groups of proteins (COGs) for each of the genome were determined.
- Comparator Vaccine Strains Clinical Isolates.
- Based on whole genome sequence data we did not observe such mutation in clinical isolates BPD1 and BPD2 reported from India (Fig.
- Circular diagram of pan-genome of vaccine strains (J445, J4445, J446, J448, BP165) and clinical strains (BPD1, BPD2) and reference strain Tohama-I.
- pertussis vaccine strains (J445, J4445, J446, J448, BP165) and clinical strains (BPD1, BPD2) and reference strain Tohama-I.
- The plot shows that progression of the pan (orange) and core (purple) genomes.
- Among the 2038 loci of the cgMLST scheme, 57 (BPD1).
- Multiple sequence alignment generated using MEGA 9, with sequence of the 23S rRNA gene of Bordetella pertussis as reference sequence, showing sequence similarity of clinical strains BPD1 and BPD2 from India with 23S rRNA gene of Bordetella pertussis of Tohama-I and Chinese vaccine strain at position A2047G based on old Tohama-I 23S rRNA gene of Tohama-I.
- The cgST profiles were found to be similar for both clinical isolates (Table 3)..
- Phylogenetic analysis of 5 vaccines, 2 clinical isolates reported from India and reference strain was compared with 166 isolates from countries using ACVs.
- pertussis vaccine strains (J445, J446, J447 and J448) showed close genetic relatedness with Indian clinical isolates and Tohama-I (bootstrap 80).
- Interestingly, isolates H ERS227757 and FR6022 were found to be closely related with Indian vac- cine strains and clinical isolates (bootstrap 80).
- Out of all the vaccine strains, BP165 was found to be distant from Indian clinical isolates.
- MLST analysis sug- gests that four vaccine strains (J445, J447, J448 and BP165) and two clinical isolates (BPD1 and BPD2) be- long to ST-2 class (Table 3).
- Vaccine and clinical isolates were subjected to allelic profiling.
- We also studied allelic profiles of other virulence-associated genes such as tracheal colonization factor (tcf-A), Borde- tella associated protein C (BapC), Adenylate cyclase (cyaA), outer membrane protein Q and Virulence associ- ated gene (Vag8) in vaccine and clinical isolates.
- The In- dian clinical isolates and vaccine strains demonstrated similar profiles as (tcfA-2-tcfA-9, bapC1, cyaA2, ompQ1- ompQ2, vag8)..
- Number of genes lost or duplicated in clinical and vaccine strains was studied as compared to reference strain Tohama-I.
- The study suggests that vaccine strains and clinical isolates displayed gene loss and duplication with no significant impact on overall gen- ome size as the number of gene lost was nearly equal to the number of genes duplicated (Table 4).
- Gen- omic deletions and ongoing gene loss are one of the apparent features observed in recent clinical isolates.
- Vaccine strains J .
- Clinical isolates BPD .
- Vaccine Strains J .
- Maximum-likelihood phylogenetic tree for Indian Bordetella pertussis isolates and vaccine strains and isolates from other geographical origins based on concatenated alignments of 2038 cgMLST gene sequences..
- We also observed a small gap in region bp) in clinical strains as compared to vaccine strains.
- All the absent genes in clinical isolates were involved in amino and nucleotide metabolism..
- pertussis vaccine strains (J445, J4445, J446, J448, BP165) and clinical strains (BPD1, BPD2) against reference strain Tohama-I.
- The linear arrangement of genomes of the vaccine strain, clinical strain genomes similarity with reference strain Tohama-I.
- Genomes are arranged with vaccine strains and clinical strains from innermost ring close to the reference genome to outermost ring from reference genome:.
- Therefore, genetic characterization of vaccine strains is important.
- We report here comparative genome ana- lysis of vaccine strains with the reference strain, clinical isolates reported from India and isolates from countries using ACV..
- Comparative whole genome analysis of clinical isolates reported from India displayed ≥95% genome similarity with reference and WCV strains used in India.
- Further, mobilome analysis of clinical isolates from India suggests slight variation in number of pseudogenes, ISs among the strains.
- pertussis vaccine strains (J445, J445, J446, J448) and clinical strains (BPD1, BPD2) against reference strain Tohama-I using a progressive Mauve2.0 algorithm.
- Indian clinical isolates as compared to isolates reported from ACV were found to cluster distinctly, indicating minimal intermixing from global strains.
- Our initial findings do support the emerging hypoth- esis that B.pertussis evolution is associated with vaccine usage and this evolution is moving at different rates in different countries.
- However, it needs validation using a larger collection of clinical isolates from countries using WCV like India.
- Nevertheless, this study provides neces- sary data on WCV strains to study the evolution and di- versity of B.pertussis in developing countries..
- The study provides a comprehensive genomic analysis of WCV strains and clinical isolates from India which will be useful in facilitating surveillance of pertussis in India and its comparisons with globally reported trends in B..
- Addition- ally, each of the genomes was manually reviewed for the copy number of transposes sequences.
- Genome neighbor report analysis of vaccine (J445, J446, J447, J448) and Clinical (BPD1, BPD2) strains.
- Mobile genetic elements (Insertion Sequences, Prophages) identified in the Bordetella vaccine and clinical strains..
- pertussis vaccine strains.
- The analysis of the data was carried out by SA, VG, SP and KP.
- Bordetella pertussis and vaccination: the persistence of a genetically monomorphic pathogen.
- Epidemic pertussis in 2012 — the resurgence of a vaccine- preventable disease.
- Genotypic variation in the Bordetella pertussis virulence factors pertactin and pertussis toxin in historical and recent clinical isolates in the United Kingdom..
- Genotypic and phenotypic characterization of Bordetella pertussis strains used in different vaccine formulations in Latin America.
- Antigenic divergence of Bordetella pertussis isolates in Taiwan.
- conservation in virulence-related genes of Bordetella pertussis isolates from the UK.
- New data on vaccine antigen deficient Bordetella pertussis isolates.
- Pertussis in the era of new strains of Bordetella pertussis..
- Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012.
- Prevalence and molecular characterization of pertactin-deficient Bordetella pertussis in the United States.
- Pertactin-negative variants of Bordetella pertussis in the United States.
- Bordetella pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.
- Characterization of Bordetella pertussis clinical isolates that do not express the tracheal colonization factor.
- Global population structure and evolution of Bordetella pertussis and their relationship with vaccination..
- Short-read whole-genome sequencing for laboratory-based surveillance of Bordetella pertussis.
- Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis.
- Genome-wide analysis of single nucleotide polymorphisms in Bordetella pertussis using comparative genomic sequencing.
- Comparative genomics of Bordetella pertussis reveals progressive gene loss in Finnish strains.
- Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.
- Insight into evolution of Bordetella pertussis from comparative genomic analysis: evidence of vaccine-driven selection.
- Epidemiological typing of Bordetella pertussis isolates: recommendations for a standard methodology.
- Genetic analysis of clinical and vaccine strains of Bordetella pertussis by pulsed-field gel electrophoresis (PFGE), multi locus sequence typing (MLST) and serotyping..
- Complete genome sequences of four Bordetella pertussis vaccine reference strains from serum Institute of India.
- Genome sequence of Bordetella pertussis vaccine strain BP 165.
- Genetic diversity of clinical Bordetella pertussis ST2 strains in comparison with vaccine reference strains of India.
- Genomic sequencing of Bordetella pertussis for epidemiology and global surveillance of whooping cough.
- The history of Bordetella pertussis genome evolution includes structural rearrangement.
- Genome structural diversity among 31 Bordetella pertussis isolates from two recent US whooping cough statewide epidemics.
- Changes in the genomic content of circulating Bordetella pertussis strains isolated from the Netherlands, Sweden, Japan and Australia: adaptive evolution or drift? BMC Genomics.
- Genomic content of Bordetella pertussis clinical isolates circulating in areas of intensive children vaccination.
- Primary transcriptome analysis reveals importance of IS elements for the shaping of the transcriptional landscape of Bordetella pertussis.
- Genomic Survey of Bordetella pertussis Diversity, United States .
- Macrolide- resistant Bordetella pertussis infection in newborn girl, France.
- High prevalence of erythromycin-resistant Bordetella pertussis in Xi ’ an, China.
- Genomic epidemiology of erythromycin-resistant Bordetella pertussis in China.
- Recent trends of antigenic variation in Bordetella pertussis isolates in Korea.
- Bordetella pertussis strain variation and evolution postvaccination.
- Genetic variation of Bordetella pertussis in Austria.
- Antigenic divergence between Bordetella pertussis clinical isolates from Moscow, Russia, and vaccine strains.
- Strain variation among Bordetella pertussis isolates circulating in Poland after 50 years of whole-cell pertussis vaccine use.
- Molecular epidemiology of Bordetella pertussis in Cambodia determined by direct genotyping of clinical specimens.
- Changes in genetic diversity of the Bordetella pertussis population in Serbia between 1953 and 2011.
- Erythromycin-resistant Bordetella pertussis.
- Genomic epidemiology of Iranian Bordetella pertussis: 50 years after the implementation of whole-cell vaccine

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