Group A Streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps

Tanaka, Mototsugu; Kinoshita-Daitoku, Ryo; Kiga, Kotaro; Sanada, Takahito; Zhu, Bao‐Ku; Okano, Tokuju; Aikawa, Chihiro; Iida, Tamako; Ogura, Yoshitoshi; Hayashi, Tetsuya; Okubo, Koshu; Kurosawa, Miho; Hirahashi, Junichi; Suzuki, Toshihiko; Nakagawa, Ichirô; Nangaku, Masaomi; Mimuro, Hitomi

doi:10.1038/s41598-020-60306-w

Cited by 12 publications

(11 citation statements)

References 39 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While neutrophil influx during severe infections is protective against S. pyogenes [63], we show that depleting neutrophils did not affect wildtype S. pyogenes MGAS8232 acute infections. These results are in contrast to findings where neutrophils are key for pathogenesis and that neutrophil ablation by αLy6G administration reduces S. pyogenes infection of the nasopharynx [47,66]. However, conventional C57BL/6 mice were used in these studies with superantigenmediated inflammation absent.…”

Section: Plos Pathogenscontrasting

confidence: 57%

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance

et al. 2022

View full text Add to dashboard Cite

Streptococcus pyogenes is a globally prominent human-specific pathogen responsible for an enormous burden of human illnesses, including >600 million pharyngeal and >100 million skin infections each year. Despite intensive efforts that focus on invasive indications, much remains unknown about this bacterium in its natural state during colonization of the nasopharynx and skin. Using acute experimental infection models in HLA-transgenic mice, we evaluated how the hyaluronic acid (HA) capsule contributes to S. pyogenes MGAS8232 infection within these limited biological niches. Herein, we demonstrate that HA capsule expression promotes bacterial burden in murine nasal turbinates and skin lesions by resisting neutrophil-mediated killing. HA capsule production is encoded by the hasABC operon and compared to wildtype S. pyogenes infections, mice infected with a ΔhasA mutant exhibited over a 1000-fold CFU reduction at 48-hours post-nasal challenge, and a 10,000-fold CFU reduction from skin lesions 72-hours post-skin challenge. HA capsule expression contributed substantially to skin lesion size development following subdermal inoculations. In the absence of capsule expression, S. pyogenes revealed drastically impeded growth in whole human blood and increased susceptibility to killing by isolated neutrophils ex vivo, highlighting its important role in resisting phagocytosis. Furthermore, we establish that neutrophil depletion in mice recovered the reduced burden by the ΔhasA mutant in both the nasopharynx and skin. Together, this work confirms that the HA capsule is a key virulence determinant during acute infections by S. pyogenes and demonstrates that its predominant function is to protect S. pyogenes against neutrophil-mediated killing.

show abstract

Section: Plos Pathogenscontrasting

confidence: 57%

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance

et al. 2022

View full text Add to dashboard Cite

show abstract

“…While neutrophil influx during severe infections is protective against S. pyogenes [63], we show that depleting neutrophils or macrophages did not affect wildtype S. pyogenes MGAS8232 acute infections. These results are in contrast to findings where neutrophils are key for pathogenesis and that neutrophil ablation by αLy6G administration reduces S. pyogenes infection of the nasopharynx [47, 65]. However, conventional C57BL/6 mice were used in these studies with superantigen-mediated inflammation absent.…”

Section: Discussionmentioning

confidence: 70%

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance

Hurst

Shannon

Craig

et al. 2022

Preprint

View full text Add to dashboard Cite

Streptococcus pyogenes is a globally prominent human-specific pathogen responsible for an enormous burden of human illnesses, including >600 million pharyngeal and >100 million skin infections each year. Despite intensive efforts that focus on invasive indications, much remains unknown about this bacterium in its natural state during colonization of the nasopharynx and skin. Using acute experimental infection models in HLA-transgenic mice, we evaluated how the hyaluronic acid (HA) capsule contributes to S. pyogenes MGAS8232 infection within these limited biological niches. Herein, we demonstrate that HA capsule expression promotes bacterial burden in murine nasal turbinates and skin lesions by resisting neutrophil-mediated killing. HA capsule production is encoded by the hasABC operon and compared to wildtype S. pyogenes infections, mice infected with a ΔhasA mutant exhibited over a 1000-fold CFU reduction at 48-hours post-nasal challenge, and a 10,000-fold CFU reduction from skin lesions 72-hours post-skin challenge. HA capsule expression contributed substantially to skin lesion size development following subdermal inoculations. In the absence of capsule expression, S. pyogenes revealed drastically impeded growth in whole human blood and increased susceptibility to killing by isolated neutrophils ex vivo, highlighting its important role in resisting phagocytosis. Furthermore, we establish that neutrophil depletion in mice, but not macrophage depletion, recovered the reduced burden by the ΔhasA mutant in both the nasopharynx and skin. Together, this work confirms that the HA capsule is a key virulence determinant during acute infections by S. pyogenes and demonstrates that its predominant function is to protect S. pyogenes against neutrophil-mediated killing.

show abstract

“…For example, deoxyribonucleases of group A S. pyogenes protect the bacteria from being trapped in NETs by digesting the NETs' web of DNA. 107 Based on whole-genome sequence data of S. sanguinis, this streptococcal species possesses a wide variety of cell wall-anchored proteins with an LPxTG motif. Among these proteins.…”

Section: Cell Surface Proteins and Enzymes (3): Cell-associated Nucleasementioning

confidence: 99%

“…Nucleases are considered to be one of the major virulence factors of various pathogenic bacteria. For example, deoxyribonucleases of group A S. pyogenes protect the bacteria from being trapped in NETs by digesting the NETs’ web of DNA 107 …”

Section: Cell Surface Proteins and Enzymes (3): Cell‐associated Nucleasementioning

confidence: 99%

Oral mitis group streptococci: A silent majority in our oral cavity

Okahashi

Nakata

Kuwata

et al. 2022

Microbiology and Immunology

View full text Add to dashboard Cite

Members of the oral mitis group streptococci including Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii are the most abundant inhabitants of human oral cavity and dental plaque, and have been implicated in infectious complications such as bacteremia and infective endocarditis. Oral mitis group streptococci are genetically close to Streptococcus pneumoniae; however, they do not produce cytolysin (pneumolysin), which is a key virulence factor of S. pneumoniae. Similar to S. pneumoniae, oral mitis group streptococci possess several cell surface proteins that bind to the cell surface components of host mammalian cells. S. sanguinis expresses long filamentous pili that bind to the matrix proteins of host cells. The cell wall–anchored nuclease of S. sanguinis contributes to the evasion of the neutrophil extracellular trap by digesting its web‐like extracellular DNA. Oral mitis group streptococci produce glucosyltransferases, which synthesize glucan (glucose polymer) from sucrose of dietary origin. Neuraminidase (NA) is a virulent factor in oral mitis group streptococci. Influenza type A virus (IAV) relies on viral NA activity to release progeny viruses from infected cells and spread the infection, and NA‐producing oral streptococci elevate the risk of IAV infection. Moreover, oral mitis group streptococci produce hydrogen peroxide (H2O2) as a by‐product of sugar metabolism. Although the concentrations of streptococcal H2O2 are low (1–2 mM), they play important roles in bacterial competition in the oral cavity and evasion of phagocytosis by host macrophages and neutrophils. In this review, we intended to describe the diverse pathogenicity of oral mitis group streptococci.

show abstract

Group A Streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps

Cited by 12 publications

References 39 publications

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance

Oral mitis group streptococci: A silent majority in our oral cavity

Contact Info

Product

Resources

About