Genomic Insight into the Spread of a Spain23f St81 (Pmen1) Capsular Variant –Serotypes 15b/C St83 Pneumococcal Clone in Taiwan

The availability and use of pneumococcal conjugate vaccines (PCV) has dramatically decreased the incidence of pneumococcal diseases caused by vaccine-targeted serotypes in children, and has also provided indirect protection to unvaccinated populations. However, the disease when replaced with non-PCV serotypes, such as 35B in the United States; 8, 12F, and 9N in England and Wales; 24F in France; and 15A in Japan, gradually decreased the overall benefit. In Taiwan, a national program providing the 13-valent pneumococcal conjugate vaccines (PCV13) to children was launched in 2013. Since 2015, PCV13 coverage has been more than 90%, leading to the incidence of invasive pneumococcal diseases (IPD) in children ＜ 5 years of age, decreasing by 70%. Based on the surveillance data from Taiwan CDC, serogroup 15 was the most common one among isolates causing IPD in children aged ＜ 5 years between 2015 and 2017. Among the 206 non-repetitive S. pneumoniae isolates collected from patients with invasive pneumococcal diseases admitted to Chang Gung Memorial Hospital during January 2013 to December 2017, we noted that serotypes 15B/C ST83 infections significantly increased from 7.1%(3/42) in 2013 to 26.7%(12/45) in 2017 (p = 0.004). ST83 was a single locus variant of ST81 which was grouped into the PMEN1 lineage by Pneumococcal Molecular Epidemiology Network (PMEN). PMEN1, predominantly circulating as a PCV7 vaccine serotype 23F (also known as Spain 23FST81), was one of the pandemic penicillin-resistant clones identified in Spain in the 1980s, subsequently spreading globally. The Spain 23FST81 clone was not only resistant to tetracycline and chloramphenicol, but also frequently developed fluoroquinolone, rifampicin and macrolide resistance. Rapid genomic evolution through high rates of recombination events featured the PMEN1 ST81 lineage in response to the selective pressure exerted by the vaccine and antibiotic use. We thought that 15B/CST83 was a capsular variant of Spain23FST81 (PMEN1). In our preliminary result, whole genome sequencing of 10 isolates of 15B/CST83 clustered together with the reference strain: Spain23F-ST81 (ATCC 700669) by phylogenomic analysis. Compared to ST81, there were 7 recombination sites in ST83. One of the recombination sites covered positions 362492-389805 which contained spi and bacteriocin. Spi is the major different allele of ST83 compared to ST81, while bacteriocin is an antibacterial toxin that mediate intra-species competition during nasopharyngeal colonization with human host. The reason for the emergence of 15B/CST83 in Taiwan only due to the vaccine and antibiotic selective pressure or the genome adaptation other than capsular switching (such as variation of bacteriocin) is interesting. The study hypothesized that the ST83 lineage has a more successful fitness advantage to undergo local expansion with comparison to its ancestor ST81. In the present study, we attempted to A. Perform whole genome sequencing, phylogenomic analysis and comparative genomics to assess evolutionary relationships and gene content differences between the ancestral clone 23FST81and its capsular variants 15B/CST83. B. Evaluate colonization ability between ST81 and ST83 lineages in mouse model C. Find genetic factors including bacteriocin responsible for better colonization in ST83 lineage

Project ID:PC10901-1611
External Project ID:MOST108-2314-B182-020-MY3