FITNESS AND GENOMIC PORTRAIT OF AUSTRALIAN 2008-2012 PERTUSSIS EPIDEMIC

Background and Aim:The resurgence of pertussis has been reported worldwide including Australia. Strain variation and pathogen adaptation have been reported in many countries in response to acellular pertussis vaccine. Single Nucleotide Polymorphism (SNP) typing separated Australian B. pertussis isolates into five clusters, known as SNP cluster I to V with the current predominant cluster I strains, also known as the ptxP3 strains worldwide.Methods:Whole genome sequencing was used to investigate the microevolution of 22 B. pertussis isolates from the latest Australian pertussis epidemic (2008-2012), all belonged to SNP profile 13 of cluster I including ten pertactin (Prn) negative. Five Australian pre-epidemic isolates were also included for analyses. Lastly, a mixed infection competition assay in a mouse model study was used to determine the differential fitness between Prn negative and Prn positive strains as well as between cluster I and cluster II strains.Results:Five SNPs differentiated epidemic isolates from pre-epidemic isolates. Phylogenetic analysis separated the 22 epidemic isolates into 5 lineages, EL1 to EL5. There were spatial and temporal clustering for the isolates analysed. However, there were also some isolates from different locality and time of isolation that were grouped together suggesting clonal spread of B. pertussis across Australia. The results revealed that cluster I strains colonised better in mice respiratory tract regardless of immunisation status and Prn negative strains have better fitness in ACV-immunised mice.Conclusion:Ongoing genomic microevolution and better fitness of ptxp3 and prn negative strains are consistent with reports of selective advantage of currently circulating B. pertussis strains.

کلیدواژه ها:

B. pertussis ، whole genome sequencing ، mixed infection competition assey