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Transcriptome comparison of M1T1 WT, AP and delta CovS strains

ABSTRACT: Group A streptococci (GAS) may engage different sets of virulence strategies, depending on the site of infection and host context. We previously isolated 2 phenotypic variants of a globally disseminated M1T1 GAS clone: a virulent wild-type (WT) strain, characterized by a SpeB(+)/SpeA(-)/Sda1(low) phenotype, and a hypervirulent animal-passaged (AP) strain, better adapted to survive in vivo, with a SpeB(-)/SpeA(+)/Sda1(high) phenotype. This AP strain arises in vivo due to the selection of bacteria with mutations in covS, the sensor part of a key 2-component regulatory system, CovR/S. To determine whether covS mutations explain the hypervirulence of the AP strain, we deleted covS from WT bacteria (DeltaCovS) and were able to simulate the hypervirulence and gene expression phenotype of naturally selected AP bacteria. Correction of the covS mutation in AP bacteria reverted them back to the WT phenotype. Our data confirm that covS plays a direct role in regulating GAS virulence. A dye-swapped cyclic design was used in this study in order that each strain could be compared across all samples in silico. For each strain treated, 2 biological replicates were each analysed in dye-swapped technical replicates, giving a total of n=10 peplicates for each strain.

ORGANISM(S): Streptococcus pyogenes

SUBMITTER: Rita Kansal

PROVIDER: E-GEOD-24246 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptome comparison of M1T1 WT, AP and delta CovS strains

Project description:Group A streptococci (GAS) may engage different sets of virulence strategies, depending on the site of infection and host context. We previously isolated 2 phenotypic variants of a globally disseminated M1T1 GAS clone: a virulent wild-type (WT) strain, characterized by a SpeB(+)/SpeA(-)/Sda1(low) phenotype, and a hypervirulent animal-passaged (AP) strain, better adapted to survive in vivo, with a SpeB(-)/SpeA(+)/Sda1(high) phenotype. This AP strain arises in vivo due to the selection of bacteria with mutations in covS, the sensor part of a key 2-component regulatory system, CovR/S. To determine whether covS mutations explain the hypervirulence of the AP strain, we deleted covS from WT bacteria (DeltaCovS) and were able to simulate the hypervirulence and gene expression phenotype of naturally selected AP bacteria. Correction of the covS mutation in AP bacteria reverted them back to the WT phenotype. Our data confirm that covS plays a direct role in regulating GAS virulence.

2010-09-22 | GSE24246 | GEO

non-M1 covRS-intact and -mutant GAS vs M1 controls

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Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes

Project description:Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase. Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation. Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.

2023-10-24 | PXD040160 | Pride

Characterisation of a novel covS SNP identified in Australian Group A Streptococcus isolates derived from the M1UK lineage

Project description:Group A Streptococcus (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1UK lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections, however the basis for its evolutionary success is not yet fully understood. During the transition to systemic disease, the M1 serotype is known to give rise to spontaneous mutations in the CovRS two-component transcriptional regulation system that confer a fitness advantage during invasive infections. Mutations that inactivate CovS function result in the de-repression of key GAS virulence factors such as Streptolysin O (SLO), a pore-forming toxin and major trigger of inflammasome/interleukin-1-dependent inflammation. Conversely, expression of the streptococcal cysteine protease SpeB, which is required during initial stages of colonisation and onset of invasive disease, is typically lost in such mutants. In this study, we identified and characterised a novel covS mutation detected in three separate invasive M1UK isolates. The resulting CovSAla318Val mutation caused a significant upregulation of SLO resulting in increased inflammasome activation in human THP-1 macrophages, indicating an enhanced inflammatory potential. Surprisingly, SpeB production was unaffected. Site-directed mutagenesis was performed to assess the impact of this mutation on virulence and global gene expression. We found that the CovSAla318Val mutation led to subtle, virulence-specific changes of the CovRS regulon compared to previously characterised covS mutations, highlighting an unappreciated level of complexity in CovRS-dependent gene regulation. Continued longitudinal surveillance is warranted to determine whether this novel covS mutation will expand in the M1UK lineage.

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2015-08-05 | E-GEOD-67533 | biostudies-arrayexpress

Transcriptome study of the covS-regulation of a Group A Streptococcus pyogenes M23ND

2015-08-05 | GSE67533 | GEO

Evaluation of covS polymorphisms on group A streptococcal global gene expression

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2010-05-15 | E-GEOD-13656 | biostudies-arrayexpress

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Comparison of gene expression in the GAS M1T1 strain 5448, wild-type vs pepO mutant

Project description:Manuscript title: The endopeptidase PepO regulates the SpeB cysteine protease and is essential for the virulence of invasive M1T1 Streptococcus pyogenes. The study investigates the effect of pepO mutation on global gene expression in GAS M1T1 strain 5448.

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