Genomic epidemiology of Streptococcus dysgalactiae subsp. equisimilis strains causing invasive disease in Norway during 2018

Alba Kaci; Christine M Jonassen; Steinar Skrede; Audun Sivertsen; Norwegian Study Group on Streptococcus dysgalactiae; Martin Steinbakk; Oddvar Oppegaard

doi:10.3389/fmicb.2023.1171913

Genomic epidemiology of Streptococcus dysgalactiae subsp. equisimilis strains causing invasive disease in Norway during 2018

Front Microbiol. 2023 Apr 17:14:1171913. doi: 10.3389/fmicb.2023.1171913. eCollection 2023.

Authors

Alba Kaci¹, Christine M Jonassen^{1

2}, Steinar Skrede^{3

4}, Audun Sivertsen⁵; Norwegian Study Group on Streptococcus dysgalactiae; Martin Steinbakk¹, Oddvar Oppegaard^{3

4}

Collaborators

Norwegian Study Group on Streptococcus dysgalactiae:
Aasmund Fostervold, Aleksandra Jakovljev, Annette Onken, Åshild Marvik, Nilsen Einar, Fredrik Müller, Ghantous Milad Chedid, Gunnar Skov Simonsen, Kyriakos Zaragkoulias, Reidar Hjetland, Roar Magne Baevre-Jensen, Sandra Åsheim, Ståle Tofteland, Tine Smedsund Dons, Truls Michael Leegaard

Affiliations

¹ Center for Laboratory Medicine, Østfold Hospital Trust, Grålum, Norway.
² Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
³ Department of Clinical Science, University of Bergen, Bergen, Norway.
⁴ Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁵ Department of Microbiology, Haukeland University Hospital, Bergen, Norway.

Abstract

Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an emerging global pathogen, yet the epidemiology and population genetics of SDSE species have not been extensively characterized.

Methods: We carried out whole genome sequencing to characterize 274 SDSE isolates causing bloodstream infections obtained through national surveillance program in 2018. We conducted multilocus sequence typing (MLST), emm-typing, core genome phylogeny, as well as investigated key features associated with virulence. Moreover, comparison to SDSE from other geographic regions were performed in order to gain more insight in the evolutionary dynamics in SDSE.

Results: The phylogenetic analysis indicated a substantial diversity of emm-types and sequence types (STs). Briefly, 17 emm-types and 58 STs were identified that formed 10 clonal complexes (CCs). The predominant ST-types were ST20 (20%), ST17 (17%), and ST29 (11%). While CC17 and CC29 clades showed a substantial heterogeneity with well-separated emm-associated subclades, the CC20 clade harboring the stG62647 emm-type was more homogenous and the most prevalent in the present study. Moreover, we observed notable differences in the distribution of clades within Norway, as well as several disseminated CCs and also distinct geographic variations when compared to data from other countries. We also revealed extensive intra-species recombination events involving surface exposed virulence factors, including the emm gene important for phylogenetic profiling.

Conclusion: Recombination events involving the emm as well as other virulence genes in SDSE, are important mechanisms in shaping the genetic variability in the SDSE population, potentially offering selective advantages to certain lineages. The enhanced phylogenetic resolution offered by whole genome sequencing is necessary to identify and delimitate outbreaks, monitor and properly characterize emerging strains, as well as elucidate bacterial population dynamics.

Keywords: SDSE; genomics; horizontal genetic transfer; surveillance studies; whole genome sequencing (WGS).

Grants and funding

This work was supported by grants from the Norwegian surveillance program for antimicrobial resistance (NORM) (Grant number: 19/16 and 20/02 to CJ and MS, as well as OO) and Center for Laboratory Medicine at Østfold Hospital Trust. The genomics Core Facility (GCF) at the University of Bergen, which is part of the NorSeq consortium provided services on the whole genome sequencing in this study; GCF is supported by major grants from the Research Council of Norway (grant no. 245979/F50) and Trond Mohn Foundation (grant no. BFS2017TMT04/BFS2017TMT08). This study was received also financial contributions from the Western Norway Regional Health Authority (grant no. 912231). SS received grants from the Norwegian Research Council under the frames of NordForsk (Project: 90456, PerAID) and ERA PerMed (Project 2018-151, PerMIT).