Key features of pneumococcal isolates recovered in Central and Northwestern Russia in 2011–2018 determined through whole-genome sequencing

Abstract

Invasive pneumococcal disease remains one of the leading causes of morbidity and mortality worldwide. In Russia, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the childhood immunization programme nationwide in 2014. As part of the Global Pneumococcal Sequencing Project (GPS), we used genome data to characterize 179 pneumococcal isolates collected from Russia in 2011-2018 to investigate the circulating pneumococcal strains using a standardized genomic definition of pneumococcal lineages (global pneumococcal sequence clusters, GPSCs), prevalent serotypes and antimicrobial resistance profiles.We observed high serotype and lineage diversity among the 179 isolates recovered from cerebrospinal fluid (n=77), nasopharyngeal swabs (n=99) and other non-sterile site swabs (n=3). Overall, 60 GPSCs were identified, including 48 clonal complexes (CCs) and 14 singletons, and expressed 42 serotypes (including non-typable). Among PCV13 serotypes, 19F, 6B and 23F were the top three serotypes while 11A, 15B/C and 8 were the top three among non-PCV13 serotypes in the collection. Two lineages (GPSC6 and GPSC47) expressed both PCV13 and non-PCV13 serotypes that caused invasive disease, and were penicillin-and multidrug-resistant (MDR), highlighting their potential to adapt and continue to cause infections under vaccine and antibiotic selective pressure. PCV13 serotypes comprised 92 % (11/12) of the CSF isolates from the children aged below 5 years; however, the prevalence of PCV13 serotype isolates dropped to 53 % (31/58) among the nasopharyngeal isolates. Our analysis showed that 59 % (105/179) of the isolates were predicted to be non-susceptible to at least one class of antibiotics and 26 % (46/179) were MDR. Four MDR lineages (GPSC1, GPSC6, GPSC10 and GPSC47) accounted for 65 % (30/46) of the MDR isolates and expressed PCV13 serotypes (93 %, 28/30).This study provides evidence of high genetic and serotype diversity contributed by a mix of globally spreading and regionally circulating lineages in Russia. The observations suggest that the PCV13 vaccine could be important in reducing both invasive disease and antimicrobial resistance. We also identify potential lineages (GPSC6 and GPSC47) that may evade the vaccine.

Disease-Associated Streptococcus pneumoniae Genetic Variation

“…One reason is that PBP2B and PBP3 are involved in the synthesis and growth of bacterial cell walls, which are crucial for the survival and virulence of pneumococci ( 43 ). In addition, a previous study revealed a potential association between penicillin resistance and GPSC1 ( 44 ), and our findings also showed that GPSC1 was associated with pneumococcal infection, suggesting that it cannot support a causal link between resistance and pneumococcal infection and may result from a lineage confounder. In summary, these infection-associated k-mers provide genetic evidence for revealing optimal risk factors for infection isolates, which may offer a theoretical basis for precise targeted interventions.…”

Population structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in Victoria, Australia

“…The GPSC6 lineage contains multiple STs (predominantly ST156) and serotypes (both 13v-PCV and non-13v-PCV but predominantly serotype 14 and 11A) but is united by a penicillin-resistant phenotype. This lineage has been observed in multiple other countries, with international studies commenting on its ability to adapt and continue to cause infection under vaccine and antimicrobial pressure [20, 48]. Despite the utility of the GPSC scheme, we could not identify any Australian pneumococcal sequences in the databases used to generate the typing scheme [20].…”