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Analysis of Streptococcus dysgalactiae subspecies equisimilis gene transcripts during experimental primate necrotizing myositis

ABSTRACT: Analysis of Streptococcus dysgalactiae subspecies equisimilis gene transcripts during experimental primate necrotizing myositis

PROVIDER: PRJNA1260997 | ENA |

REPOSITORIES: ENA

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Analysis of Streptococcus dysgalactiae subspecies equisimilis gene transcripts during experimental primate necrotizing myositis

Project description:Streptococcus dysgalactiae subspecies equisimilis (SDSE) is a Gram-positive bacterial pathogen capable of causing various infections in humans. Recently, isolates of SDSE emm type stG62647 have emerged as a cause of severe invasive infections, including necrotizing myositis. However, the molecular processes underlying these infections remain poorly understood. To address this gap, we performed RNAseq analysis to examine SDSE gene transcript levels during experimental necrotizing myositis infection in non-human primates, an animal phylogenetically closely related to humans. We analyzed the transcriptomes of two related SDSE stG62647 human isolates (MGCS36044 and MGCS36089) during necrotizing myositis infection in six non-human primates. The transcriptome from in vitro growth in nutrient-rich media differed considerably from that of SDSE bacteria grown in vivo in experimental necrotizing myositis, with 254 genes differentially expressed, indicating extensive genetic adaptation in infected skeletal muscle. Notably, we observed marked upregulation of ihk-irr genes encoding a two-component regulatory system that promotes evasion of phagocytosis and resistance to killing by human polymorphonuclear leukocytes in Streptococcus pyogenes. Similarly, genes comprising the sag operon encoding the streptolysin S cytolytic toxin virulence factor demonstrated very high transcript abundance in vivo. Additionally, we present evidence that a 40-nt deletion in fasB alters expression of ska, encoding streptokinase. Collectively, our data provide new insights into the SDSE genes transcribed in vivo, thereby enhancing our understanding of the molecular basis of pathogen and primate host interactions. The SDSE genes identified in this study offer promising targets for future studies on molecular pathogenesis and therapeutics interventions.

2025-07-02 | GSE296749 | GEO

Integrative genomic, virulence, and transcriptomic analysis of emergent Streptococcus dysgalactiae subspecies equisimilis (SDSE) emm type stG62647 isolates causing human infections

Project description:Streptococcus dysgalactiae subspecies equisimilis (SDSE) is a Gram-positive bacterial pathogen that infects humans and is closely related to group A streptococcus (GAS). Compared to GAS, far less is known about SDSE pathobiology. Increased rates of invasive SDSE infections have recently been reported in many countries. One SDSE emm type, stG62647, is known to cause severe diseases, including necrotizing soft-tissue infections, endocarditis, and osteoarticular infections. To increase our understanding of the molecular pathogenesis of stG62647 SDSE isolates causing human infections, we sequenced to closure the genomes of 120 stG62647 SDSE isolates. The genomes varied in size from 2.1 to 2.24 megabase pairs. Consistent with previous data, the great majority of stG62647 isolates had IS1548 integrated into the silB gene, thereby inactivating it. Regions of difference in gene content, including putative mobile genetic elements, were the largest source of genomic diversity. All 120 stG62647 isolates were assayed for virulence using a well-established mouse model of necrotizing myositis. An unexpectedly wide range of virulence was identified (20% to 95%), as assessed by near-mortality data. To explore the molecular mechanisms underlying virulence differences, we analyzed RNAseq transcriptome profiles for 38 stG62647 isolates (comprising the 19 least and most virulent) grown in vitro. Genetic polymorphisms were identified from whole-genome sequence data. Collectively, the results suggest that these SDSE isolates use multiple genetic pathways to achieve an altered virulence phenotype. Our study integrates genomic, mouse virulence, and RNAseq data to advance our understanding of SDSE pathobiology and its molecular pathogenesis.

2024-07-20 | GSE272047 | GEO

Streptococcus dysgalactiae subsp. equisimilis

Project description:Streptococcus dysgalactiae subsp. equisimilis

| PRJEB43000 | ENA

Comparative genomic hybridization of disease causing strains of Streptococcus dysgalactiae ssp.

Project description:Group C Streptococcus dysgalactiae subsp. dysgalactiae (GCS) field strains causative of bovine mastitis and group C or group G Streptococcus dysgalactiae subsp. equisimilis (GCS/GGS) isolates from human infections were tested for the presence of virulence genes employing a microarray containing 220 virulence genes of S. pyogenes (GAS).

2011-05-05 | E-MEXP-3168 | biostudies-arrayexpress

Streptococcus dysgalactiae subsp. equisimilis

Project description:Streptococcus dysgalactiae subsp. equisimilis Genome Diversity

| PRJNA327242 | ENA

Streptococcus dysgalactiae subsp. equisimilis

Project description:Invasive Streptococcus dysgalactiae subsp. equisimilis 2011-2023

| PRJNA1133199 | ENA

Immunoglobulin Attenuates Streptokinase-Mediated Virulence in Streptococcus dysgalactiae Subspecies equisimilis Necrotizing Fasciitis.

Project description:Background:Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated with Streptococcus dysgalactiae subspecies equisimilis (SDSE). Methods:We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors. Results:We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model. Conclusions:These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs.

| S-EPMC7263839 | biostudies-literature

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Project description:Streptococcus dysgalactiae subsp. equisimilis Genome sequencing and assembly

| PRJNA811777 | ENA

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Streptococcus dysgalactiae subsp. equisimilis

Project description:Streptococcus dysgalactiae subsp. equisimilis Genome sequencing and assembly

| PRJNA552440 | ENA