Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells’ Type 1 Interferon Response

Keller, Nadia; Woytschak, Janine; Heeb, Lukas E. M.; Maggio, Ewerton Marques; Shambat, Srikanth Mairpady; Snäll, Johanna; Hyldegaard, Ole; Boyman, Onur; Norrby‐Teglund, Anna

doi:10.1016/j.jid.2018.11.027

Cited by 13 publications

(9 citation statements)

References 44 publications

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“…The virulence factor streptococcal DNase sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and Toll-like receptor 9 (TLR9) signaling. This factor impairs plasmacytoid dendritic cell recruitment by reducing interferon (IFN)-1 levels at the site of infection and destabilizes DNA via the host protein HMGB1 (high mobility group box 1), which may decrease IFN-1 levels at the site of infection (1 levels at the site of infection ( Uchiyama et al, 2012 ; Keller et al, 2019 ). Our WGS data showed that sda was specifically expressed by emm 12.0 strains.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of Streptococcus pyogenes Isolated From Chinese Children With Different Diseases

Liang

et al. 2021

Front. Microbiol.

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Streptococcus pyogenes is a bacterial pathogen that causes a wide spectrum of clinical diseases exclusively in humans. The distribution of emm type, antibiotic resistance and virulence gene expression for S. pyogenes varies temporally and geographically, resulting in distinct disease spectra. In this study, we analyzed antibiotic resistance and resistance gene expression patterns among S. pyogenes isolates from pediatric patients in China and investigated the relationship between virulence gene expression, emm type, and disease categories. Forty-two representative emm1.0 and emm12.0 strains (n = 20 and n = 22, respectively) isolated from patients with scarlet fever or obstructive sleep apnea-hypopnea syndrome were subjected to whole-genome sequencing and phylogenetic analysis. These strains were further analyzed for susceptibility to vancomycin. We found a high rate and degree of resistance to macrolides and tetracycline in these strains, which mainly expressed ermB and tetM. The disease category correlated with emm type but not superantigens. The distribution of vanuG and virulence genes were associated with emm type. Previously reported important prophages, such as φHKU16.vir, φHKU488.vir, Φ5005.1, Φ5005.2, and Φ5005.3 encoding streptococcal toxin, and integrative conjugative elements (ICEs) such as ICE-emm12 and ICE-HKU397 encoding macrolide and tetracycline resistance were found present amongst emm1 or emm12 clones from Shenzhen, China.

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Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of Streptococcus pyogenes Isolated From Chinese Children With Different Diseases

Liang

et al. 2021

Front. Microbiol.

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“…DNase inhibitors, such as DR396, can limit HMGB1 release during cell death 223 , 224 . Interestingly, bacterial-derived DNase can interfere with DNA stability through HMGB1, thereby impairing the type 1 IFN response in infection 225 . It is expected that the DNA sensor pathway may link cell death, HMGB1 release, and the immune response.…”

Section: Passive Release Of Hmgb1mentioning

confidence: 99%

The mechanism of HMGB1 secretion and release

2022

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High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 is a DNA chaperone that maintains the structure and function of chromosomes. In the cytoplasm, HMGB1 can promote autophagy by binding to BECN1 protein. After its active secretion or passive release, extracellular HMGB1 usually acts as a damage-associated molecular pattern (DAMP) molecule, regulating inflammation and immune responses through different receptors or direct uptake. The secretion and release of HMGB1 is fine-tuned by a variety of factors, including its posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, and methylation) and the molecular machinery of cell death (e.g., apoptosis, pyroptosis, necroptosis, alkaliptosis, and ferroptosis). In this minireview, we introduce the basic structure and function of HMGB1 and focus on the regulatory mechanism of HMGB1 secretion and release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases and tissue damage.

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“…Mice infected with a GAS Sda1 mutant, produced higher type I IFN levels, which reduced bacterial numbers and lesion sizes [36]. While a phenotype was not observed in IFNAR knockout (KO) mice, this is presumably due to the active suppression mediated by Sda1.…”

Section: The Roles Of Type I Ifns In Bacterial Infectionsmentioning

confidence: 99%