Streptolysin S induces pronounced calcium-ion influx-dependent expression of immediate early genes encoding transcription factors

Yamada, Takuya; Yamamori, Yugo; Matsuda, Nanami; Nagamune, Hideaki; Ohkura, Kazuto; Tomoyasu, Toshifumi; Tabata, Atsushi

doi:10.1038/s41598-023-40981-1

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…β-hemolytic S. anginosus subsp. anginosus (SAA) induced cytotoxicity in cocultured HSC-2 cells in vitro , suggesting a potential association between S. anginosus and SLS ( 38 ). However, contradictory findings emerged from Asam et al ( 39 ), which argues SLS produced by SAA fails to induce cytotoxicity in THP-1 cells and human granulocytes.…”

Section: Discussionmentioning

confidence: 99%

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages

Senthil Kumar,

Gunda,

Reinartz

et al. 2024

Infect Immun

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Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers, while Streptococcus mitis is linked to oral cancer. However, no study has investigated the mechanistic links between these Streptococcus species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by S. anginosus and S. mitis in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with S. anginosus exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1β, NOS2, and COX2, accompanied by enhanced NF-κB activation. In contrast, S. mitis -infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with S. anginosus compared with S. mitis . At the 24-h time point, the presence of S. anginosus led to reduced extracellular itaconate, while S. mitis triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how S. anginosus and S. mitis , two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection. IMPORTANCE The surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome’s influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis. Streptococcus anginosus , a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to S. anginosus compared with the early colonizer Streptococcus mitis as an important first step toward understanding the impact of distinct oral Streptococcus species on the host immune response, which is an understudied determinant of OSCC development and progression.

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Section: Discussionmentioning

confidence: 99%

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages

Senthil Kumar,

Gunda,

Reinartz

et al. 2024

Infect Immun

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“…When these cells were incubated with supernatants from SLS-producing streptococci, the inflammatory cytokines IL-6 and CXCL8 were significantly upregulated, along with genes involved in the early growth response and genes in the Fos and Jun families. These changes were linked to the SLS-dependent influx of Ca 2+ ions into the HSC-2 cells, further indicating a connection between SLS activity and ion flux ( Yamada et al., 2023 ). In addition, SLS was identified ( von Beek et al., 2019 ) as an important factor from S. equi that triggers p38 and Erk1/2 signaling in murine bone-marrow derived mast cells.…”

Section: Streptolysin Smentioning

confidence: 94%

“…For example, SLS from S. anginosus subsp. anginosus induces the expression of several genes in human oral squamous cell carcinoma (HSC-2) cells ( Yamada et al., 2023 ). When these cells were incubated with supernatants from SLS-producing streptococci, the inflammatory cytokines IL-6 and CXCL8 were significantly upregulated, along with genes involved in the early growth response and genes in the Fos and Jun families.…”

Section: Streptolysin Smentioning

confidence: 99%

Streptococcal peptides and their roles in host-microbe interactions

Wahlenmayer,

Hammers

2023

Front. Cell. Infect. Microbiol.

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The genus Streptococcus encompasses many bacterial species that are associated with hosts, ranging from asymptomatic colonizers and commensals to pathogens with a significant global health burden. Streptococci produce numerous factors that enable them to occupy their host-associated niches, many of which alter their host environment to the benefit of the bacteria. The ability to manipulate host immune systems to either evade detection and clearance or induce a hyperinflammatory state influences whether bacteria are able to survive and persist in a given environment, while also influencing the propensity of the bacteria to cause disease. Several bacterial factors that contribute to this inter-species interaction have been identified. Recently, small peptides have become increasingly appreciated as factors that contribute to Streptococcal relationships with their hosts. Peptides are utilized by streptococci to modulate their host environment in several ways, including by directly interacting with host factors to disrupt immune system function and signaling to other bacteria to control the expression of genes that contribute to immune modulation. In this review, we discuss the many contributions of Streptococcal peptides in terms of their ability to contribute to pathogenesis and disruption of host immunity. This discussion will highlight the importance of continuing to elucidate the functions of these Streptococcal peptides and pursuing the identification of new peptides that contribute to modulation of host environments. Developing a greater understanding of how bacteria interact with their hosts has the potential to enable the development of techniques to inhibit these peptides as therapeutic approaches against Streptococcal infections.

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Roles of intralesional bacteria in the initiation and progression of oral squamous cell carcinoma

Luo,

Lv,

Lou

et al. 2024

Cancer Medicine

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BackgroundOral squamous cell carcinoma (OSCC) is the predominant form of head and neck cancer, often diagnosed at late stages, resulting in a poor prognosis. Recent studies indicate a potential association between OSCC and microbial presence. Microorganisms have been identified in various tumors and lesions, including OSCC and oral potentially malignant disorders (OPMDs). Intralesional microbiota are considered important components of the tumor microenvironment (TME) and may contribute to carcinogenesis.MethodsSources were collected through thorough searches of databases PubMed and Embase. The review focused on microbial characteristics, potential origins, and their impact on cancer progression.ResultsBacteria display varying abundance and diversity throughout the stages of OSCC and OPMDs. Intraleisional bacteria may have diverse sources, including not only oral plaque and saliva but also potentially the gut. Intralesional bacteria have both pro‐carcinogenic and anti‐carcinogenic effects, affecting processes like cell proliferation, invasion, and immune response.ConclusionsIntralesional microbiota are crucial in OSCC and OPMDs, influencing both disease progression and treatments. Despite their significance, challenges like inconsistent sampling and microbial identification remain. Future research is required to fully understand their role and improve clinical applications.

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Streptolysin S induces pronounced calcium-ion influx-dependent expression of immediate early genes encoding transcription factors

Cited by 4 publications

References 54 publications

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages

Streptococcal peptides and their roles in host-microbe interactions

Roles of intralesional bacteria in the initiation and progression of oral squamous cell carcinoma

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