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, 7 (1), 7589

Emergence of a Streptococcus Dysgalactiae Subspecies Equisimilis stG62647-lineage Associated With Severe Clinical Manifestations

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Emergence of a Streptococcus Dysgalactiae Subspecies Equisimilis stG62647-lineage Associated With Severe Clinical Manifestations

Oddvar Oppegaard et al. Sci Rep.

Abstract

Increasing incidence rates of invasive Streptococcus dysgalactiae subspecies equisimilis (SDSE) infections have been reported worldwide, but the evolutionary mechanisms underlying this development remain elusive. Through prospective surveillance of invasive SDSE infections in western Norway, we observed the emergence of a novel and virulent SDSE genotype, stG62647. This emm-type, rarely encountered as a cause of invasive disease during 1999-2012, emerged in 2013 as the predominant SDSE-genotype. The stG62647-infections were associated with an aggressive clinical course, including the occurrence of streptococcal toxic shock syndrome, necrotizing soft-tissue infections and endocarditis. All the invasive stG62647-isolates were subjected to whole genome sequencing, attempting to explore the genetic events underpinning its epidemicity. Although 10% of the genomes was unique for stG62647-genotype, notably 18 out of 19 isolates contained a disrupted streptococcal invasive locus (sil) due to the insertion of a transposase, IS1548, into the silB-gene. We postulate that the virulence of stG6267-isolates could be partly attributable to the abrogation of the attenuating control normally exerted by this regulon, although experimental verification was not performed. To the best of our knowledge, this is the first study employing large scale whole genome sequencing to illuminate the genetic landscape of epidemic lineages in SDSE.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
The temporal distribution of emm-types associated with 267 cases of invasive SDSE-disease encountered during 1999–2015. stG62647 was the predominant emm-type in the period 2013–2015, comprising approximately 20% of the invasive SDSE-isolates. The category “Other” includes stG166b (12), stG2078 (9), stG652 (8), stC5345 (4), stC36 (2), stC2574 (2), stC3852 (2), stG4831 (2), stG5420 (2), stC1400 (1), stC7901 (1), stG12 (1), stG120 (1), stG245 (1), stG4222 (1), stG507 (1), stG653 (1), stG6792 (1), stG840 (1) and 29 isolates not available for emm-typing.
Figure 2
Figure 2
Phylogenetic tree of the stG62647-isolates based on core-genome SNP-analysis. (a) Phylogenetic tree of all 19 stG62647-isolates. (b) Phylogenetic tree of the 18 stg62647-isolates belonging to clonal complex 20. The ST17-isolate (T666) was omitted from the analysis to increase the phylogenetic resolution of the tree. Scales indicate substitutions per site. MLST-profile is indicated in parentheses.
Figure 3
Figure 3
Genetic arrangement of the streptococcal invasive locus in the CC20-isolates. The sil-locus in the CC20 isolates has a transposase, IS1548, inserted into the silB-gene. silB encodes a sensory kinase activating the putative DNA response regulator encoded by silA. This leads to increased transcription of the virulence attenuating pheromone encoded by silCR, and suppression of the virulence associated silC-gene. The SilC-peptide is exported from the cell by the transporter-proteins SilD and SilE. Scale indicates nucleotide position. This disrupted sil-locus is deposited in GenBank under the accession code KY807567.

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