<i>Streptococcus gordonii</i>
            programs epithelial cells to resist ZEB2 induction by
            <i>Porphyromonas gingivalis</i>

Ohshima, Jun; Wang, Qian; Fitzsimonds, Zackary R.; Miller, Daniel P.; Sztukowska, Maryta; Jung, Young‐Jung; Hayashi, Mikako; Whiteley, Marvin; Lamont, Richard J.

doi:10.1073/pnas.1900101116

Cited by 50 publications

(72 citation statements)

References 94 publications

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“…The adaptation of a community lifestyle provides physiologic support to its constituent species, lower levels of environmental stress, and promotes the chance of survival [75]. S. gordonii is considered as a homeostatic commensal that is capable of mitigating the activity of P. gingivalis and modulating the host signaling [78][79][80][81][82].…”

Section: Mechanism Of P Gingivalis Invasion and Persistence Within Tmentioning

confidence: 99%

“…transition and inflammatory responses within the periodontal tissues [80,81]. P. gingivalis mediated ZEB2 regulation occurs through pathways involving β-catenin and Forkhead box protein O1 (FOXO1).…”

Section: Mechanism Of P Gingivalis Invasion and Persistence Within Tmentioning

confidence: 99%

“…The SerB even remains functionally viable within the cells by interacting with other bacteria proteins. For example, SerB of P. gingivalis binds to the Heat Shock Protein (HSP) and GAPDH (glyceraldehyde 3 phosphate dehydrogenase) of Streptococcus oralis within the periodontal tissues to increase the inflammatory response [80,83,100] P. gingivalis also inhibit, TLRs, E-selectin and intercellular adhesion molecular (ICAM) expression on the endothelial cell surface and binds to the non-chemotactic methionyl peptides receptor to inhibits the neutrophil chemotactic gradient, leukocyte adhesion, and recruitment of neutrophil to the site of inflammation [150][151][152][153][154][155][156][157][158][159][160]. The reduced chemotaxis decreases the rate of phagocytosis and facilitates the growth of the entire microbial community.…”

Section: Neutrophil Dysfunction and Increase Cytokine Productionmentioning

confidence: 99%

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Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update

Chopra

Bhat

Sivaraman

2020

Journal of Oral Microbiology

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Porphyromonas. gingivalis (P. gingivalis) is an obligate, asaccharolytic, gram-negative bacteria commonly associated with increased periodontal and systemic inflammation. P. gingivalis is known to survive and persist within the host tissues as it modulates the entire ecosystem by either engineering its environment or modifying the host's immune response. It interacts with various host receptors and alters signaling pathways of inflammation, complement system, cell cycle, and apoptosis. P. gingivalis is even known to induce suicidal cell death of the host and other microbes in its vicinity with the emergence of pathobiont species. Recently, new molecular and immunological mechanisms and virulence factors of P. gingivalis that increase its chance of survival and immune evasion within the host have been discovered. Thus, the present paper aims to provide a consolidated update on the new intricate and unique molecular mechanisms and virulence factors of P. gingivalis associated with its survival, persistence, and immune evasion within the host.

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Section: Mechanism Of P Gingivalis Invasion and Persistence Within Tmentioning

confidence: 99%

Section: Mechanism Of P Gingivalis Invasion and Persistence Within Tmentioning

confidence: 99%

Section: Neutrophil Dysfunction and Increase Cytokine Productionmentioning

confidence: 99%

See 1 more Smart Citation

Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update

Chopra

Bhat

Sivaraman

2020

Journal of Oral Microbiology

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“…However, in focusing on exploring the role of species that are enriched in the tumors, i.e., the pathobionts, researchers seem to have largely ignored the health-associated species that in fact may be playing a protective role against oral cancer. Indeed, Ohshima et al ( 2019 ) have very recently found Streptococcus gordonii , a health-associated species, to antagonize the pro-cancer phenotypes induced by P. gingivalis , highlighting the need to explore the other side of the relationship between the microbiome and oral cancer.…”

Section: Introductionmentioning

confidence: 99%

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Baraniya

Jain

Lucarelli

et al. 2020

Front. Cell. Infect. Microbiol.

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While extensive literature exists about the role of oral bacterial pathogens like Porphyromonas gingivalis and Fusobacterium nucleatum in oral squamous cell carcinoma (OSCC), the role of health-associated species has been largely unexplored. In this study, we assessed the effect of Streptococcus mitis, Rothia mucilaginosa, Neisseria flavescens, Haemophilus parainfluenzae, Lautropia mirabilis , and Veillonella parvula on proliferation and expression of marker genes (IL-6, TNF-α, MMP3, CD36, CCD1, and NANOG) in OSCC cell lines CAL27, SCC25, and SCC4. Porphyromonas gingivalis was included as a pathogenic control. Both bacterial lysates (3 concentrations) and live cells (3 MOIs) were tested. S. mitis, H. parainfluenzae , and N. flavescens resulted in substantial, dose-dependent reduction of proliferation, which was found to be mediated by H 2 O 2 for the former and intracellular infection in the latter two species. However, only H. parainfluenzae showed differential antiproliferative effect against the cancer cell lines vs. the normal control (TIGKs). In the gene expression assays, the health-associated species mostly downregulated CD36, a gene that plays an important role in tumor growth and metastasis, while P. gingivalis upregulated it. IL6 and TNF expression, on the other hand, was upregulated by almost all species, particularly the Gram-negatives including P. gingivalis . The effect on other genes was less evident and varied significantly by cell line. This exploratory study is the first insight into how health-associated bacteria may interact with OSCC. Further studies to explore whether the observed effects may have implications for the prevention or treatment of oral cancer are warranted.

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“…TIGKs (telomerase immortalized gingival keratinocytes) were kindly provided by Dr. Richard Lamont (University of Louisville). TIGKs have been established by immortalizing primary gingival epithelial cells and share similar morphology, karyotype, expression of cytokeratin and Toll-like receptors, and kinetics of invasion of P. gingivalis with parental cells and widely used in preclinical studies (21)(22)(23). TIGKs were maintained in LifeLine DermaLife medium with supplements (rh-insulin, L-glutamine, epinephrine, Apo-Transferrin, rh-TGFα, Extract P, Hydrocortisone, LifeLine technology) as described previously (21).…”

Section: Bacteria and Cell Culturementioning

confidence: 99%

A20 Restricts Inflammatory Response and Desensitizes Gingival Keratinocytes to Apoptosis

Mooney

Xia

et al. 2020

Front. Immunol.

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The pathophysiology of periodontal disease involves a perturbed immune system to a dysbiotic microflora leading to unrestrained inflammation, collateral tissue damage, and various systemic complications. Gingival epithelial cells function as an important part of immunity to restrict microbial invasion and orchestrate the subsequent innate responses. A20 (TNFAIP3), an ubiquitin-editing enzyme, is one of the key regulators of inflammation and cell death in numerous tissues including gastrointestinal tract, skin, and lungs. Emerging evidence indicates A20 as an essential molecule in the oral mucosa as well. In this study, we characterized the role of A20 in human telomerase immortalized gingival keratinocytes (TIGKs) through loss and gain of function assays in preclinical models of periodontitis. Depletion of A20 through gene editing in TIGKs significantly increased IL-6 and IL-8 secretion in response to Porphyromonas gingivalis infection while A20 over-expression dampened the cytokine production compared to A20 competent cells through modulating NF-κB signaling pathway. In the subsequent experiments which assessed apoptosis, A20 depleted TIGKs displayed increased levels of cleaved caspase 3 and DNA fragmentation following P. gingivalis infection and TNF/CHX challenge compared to A20 competent cells. Consistently, there was reduced apoptosis in the cells overexpressing A20 compared to the control cells expressing GFP further substantiating the role of A20 in regulating gingival epithelial cell fate in response to exogenous insult. Collectively, our findings reveal first systematic evidence and demonstrate that A20 acts as a regulator of inflammatory response in gingival keratinocytes through its effect on NF-κB signaling and desensitizes cells to bacteria and cytokine induced apoptosis in the oral mucosa. As altered A20 levels can have profound effect on different cellular responses, future studies will determine whether A20-targeted therapies can be exploited to restrain periodontal inflammation and maintain oral mucosa tissue homeostasis.

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Streptococcus gordonii programs epithelial cells to resist ZEB2 induction by Porphyromonas gingivalis

Cited by 50 publications

References 94 publications

Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update

Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

A20 Restricts Inflammatory Response and Desensitizes Gingival Keratinocytes to Apoptosis

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