Analysis of original pertussis vaccine strains
We have compared genomic organization and transcriptomic and proteomic profiles of Czech clinical isolates collected between 2008 and 2015, Czech vaccine strains isolated from 1954 to 1965 and reference strain Tohama I. The SNP-based phylogenetic analysis of Czech strains and more than 350 complete B. pertussis genome sequences currently deposited in the GenBank showed that Czech isolates cluster with isolates from other countries demonstrating worldwide spread and lack of geographical signature. Importantly, this result indicates that our data obtained with Czech isolates are applicable to strains from other countries. When compared to vaccine strains, genome size of Czech recent isolates was substantially reduced thereby confirming ongoing gene loss process within the global population of B. pertussis. The alignment of closed genomes revealed that all genomes contain large-scale structural rearrangements when compared to the reference strain Tohama I.
According to their genome organization, sequenced strains could be classified into eight groups. The phylogenetic tree based on the genome organization of Czech strains demonstrated clear separation of historical and recent Czech isolates. Importantly, subsequent RNA-seq and LC-MS/MS analyses clearly indicated that genomic variations translated into discretely separated transcriptomic and proteomic profiles. Recent isolates displayed increased expression of flagellar genes and decreased expression of polysaccharide capsule operon compared to vaccine strains. Furthermore, compared to reference strain Tohama I, Czech strains exhibited increased expression of genes encoding Type III secretion system apparatus (T3SS). In spite of 50 years of vaccination, Czech vaccine strains differ from recent isolates to a lesser extent than from another vaccine strain Tohama I. Collectively, our data suggest that besides shaping the evolution of B. pertussis on a genomic scale, the genome rearrangements affect also the global gene expression and proteomic profiles. We assume that this mechanism counterbalances the low level of genetic variability observed in this pathogen and significantly contributes to adaptation of global population of B. pertussis.