Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion

Wierzbicki, Igor H.; Campeau, Anaamika; Dehaini, Diana; Holay, Maya; Wei, Xiaoli; Greene, Trever T; Sands, Jenna S.; Lamsa, Anne; Zúñiga, Elina I.; Pogliano, Kit; Fang, Ronnie H.; LaRock, Christopher N.; Zhang, Liangfang; Gonzalez, David J.

doi:10.1016/j.celrep.2019.11.001

Cited by 27 publications

(23 citation statements)

References 65 publications

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“…Here, we demonstrate that 5448AP is not only resistant to neutrophil-mediated killing but proliferates in the presence of functional neutrophils. GAS survival has been demonstrated intracellularly in murine neutrophils and human macrophages ( Medina et al., 2003a ; Medina et al., 2003b ; O’Neill et al., 2016 ) and can even be facilitated by host red blood cells ( Wierzbicki et al., 2019 ). Increased 5448AP proliferation may result from the reduction in neutrophil ROS response during infection.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus pyogenes M1T1 Variants Induce an Inflammatory Neutrophil Phenotype Including Activation of Inflammatory Caspases

Williams

Geraghty

et al. 2021

Front. Cell. Infect. Microbiol.

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Invasive infections due to group A Streptococcus (GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond to GAS. The neutrophil response to GAS was characterised in response to two M1T1 isolates; 5448 and animal passaged variant 5448AP. Co-incubation of neutrophils with 5448AP resulted in proliferation of GAS and lowered the production of reactive oxygen species when compared with 5448. Infection with both strains invoked neutrophil death, however apoptosis was reduced in response to 5448AP. Both strains induced neutrophil caspase-1 and caspase-4 expression in vitro, with inflammatory caspase activation detected in vitro and in vivo. GAS infections involving strains such as 5448AP that promote an inflammatory neutrophil phenotype may contribute to increased inflammation yet ineffective bacterial eradication, contributing to the severity of invasive GAS infections.

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Section: Discussionmentioning

confidence: 99%

Streptococcus pyogenes M1T1 Variants Induce an Inflammatory Neutrophil Phenotype Including Activation of Inflammatory Caspases

Williams

Geraghty

et al. 2021

Front. Cell. Infect. Microbiol.

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“…were observed correlated with red blood cell count ( p < 0.05), such as S. mitis (p= 1.99 × 10 −12 ) and S. pseudopneumoniae (p = 4.51 × 10 −12 ) . These results suggested that commensal Streptococcus species might utilize red blood cells as camouflage to avoid being engulfed by phagocytic immune cells in addition to the well-known group A Streptococcus ( S. pyogenes ) 33 . Our results also supported previous findings that Streptococcus spp .…”

Section: Resultsmentioning

confidence: 95%

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

Liu

Tong

Zhu

et al. 2021

Preprint

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The oral microbiota contains billions of microbial cells, which could contribute to diseases in a number of body sites. Challenged by eating, drinking and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1,915 individuals, for both the tongue dorsum and saliva. Five genetic loci, APPL2, SLC2A9 and MGST1 associated with tongue dorsum, LOC102723769-OR11H1-POTEH and MTRNR2L1-LOC105371703-MIR4522 associated with salivary microbial features, reached study-wide significance (p < 3.16 * 10-11). Further analyses confirmed 6 genome-wide significant loci shared between tongue dorsum and saliva. For example, the dental caries pathogen Prevotella melaninogenica associated with MARK2-RCOR2; the periodontitis bacteria Treponema associated with CCL26-CCL24 and Porphyromonas associated with CSMD1 at both niches. Human genetics account for at least 10% of oral microbiome differences between individuals. Machine learning models showed that polygenetic risk score dominated over oral microbiome in predicting predisposing risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

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“…Fractions were next analyzed using tandem mass spectrometry (MS2/MS3) on an Orbitrap Fusion mass spectrometer (Thermo Fisher Scientific) with an in-line EASY-nLC 1000 instrument (Thermo Fisher Scientific). Separation and acquisition settings were performed using the previously defined methods [ 44 ].…”

Section: Methodsmentioning

confidence: 99%

Unique virulence role of post-translocational chaperone PrsA in shaping Streptococcus pyogenes secretome

Campeau

Liu

et al. 2021

Virulence

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Streptococcus pyogenes (group A Streptococcus , GAS) is a strict human pathogen causing a broad spectrum of diseases and a variety of autoimmune sequelae. The pathogenesis of GAS infection mostly relies on the production of an extensive network of cell wall-associated and secreted virulence proteins, such as adhesins, toxins, and exoenzymes. PrsA, the only extracellular parvulin-type peptidyl-prolyl isomerase expressed ubiquitously in Gram-positive bacteria, has been suggested to assist the folding and maturation of newly exported proteins to acquire their native conformation and activity. Two PrsA proteins, PrsA1 and PrsA2, have been identified in GAS, but the respective contribution of each PrsA in GAS pathogenesis remains largely unknown. By combining comparative proteomic and phenotypic analysis approaches, we demonstrate that both PrsA isoforms are required to maintain GAS proteome homeostasis and virulence-associated traits in a unique and overlapping manner. The inactivation of both PrsA in GAS caused remarkable impairment in biofilm formation, host adherence, infection-induced cytotoxicity, and in vivo virulence in a murine soft tissue infection model. The concordance of proteomic and phenotypic data clearly features the essential role of PrsA in GAS full virulence.

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Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion

Cited by 27 publications

References 65 publications

Streptococcus pyogenes M1T1 Variants Induce an Inflammatory Neutrophil Phenotype Including Activation of Inflammatory Caspases

Streptococcus pyogenes M1T1 Variants Induce an Inflammatory Neutrophil Phenotype Including Activation of Inflammatory Caspases

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

Unique virulence role of post-translocational chaperone PrsA in shaping Streptococcus pyogenes secretome

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