Coadministration of the cyanobacterial lipopolysaccharide antagonist CyP with antibiotic inhibits cytokine production by an in vitro meningitis model infected with Neisseria meningitidis

Oliver, Rebecca; Staples, Karl J.; Heckels, John E.; Rossetti, Carlo; Molteni, Monica; Christodoulides, Myron

doi:10.1093/jac/dks031

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…LPS extracted from Oscillatoria planktothrix FP1 (so-called CyP) has been shown to selectively antagonize LPS from bacteria via binding to MD-2 protein [159]. CyP inhibits the production of pro-inflammatory cytokines and affects microRNA expression in different in vitro models [160,161].…”

Section: Table 3 Overview Of Cylindrospermopsin Effects On the Gastromentioning

confidence: 99%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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Background: Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro-, and neurotoxicity, than for effects on the gastrointestinal tract and the associated lymphoid tissue. Main body: The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human health-relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects, or both. Furthermore, cyanobacterial bloom lipopolysaccharides, other less studied metabolites and their mixtures have been also implicated to have a role in gastrointestinal inflammation. Conclusion: The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. In addition, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites such as aeruginosins, have to be toxicologically evaluated at distinct levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, which can be expected in drinking water supplies.

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Section: Table 3 Overview Of Cylindrospermopsin Effects On the Gastromentioning

confidence: 99%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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“…CyP was shown to act as a competitive inhibitor of E. coli LPS binding to the receptor complex on human dendritic cells in vitro, and subsequently suppress downstream gene transcription and cytokine production. CyP significantly inhibited the secretion of IL-6, IL-8, monocyte chemoattractant protein (MCP)-1 and regulated upon activation normal T cell expressed and secreted (RANTES) by meningioma cell lines and meningioma-macrophage co-cultures challenged with either live meningococci or bacterial components [97], but administration of CyP with antibiotics has not been studied in experimental bacterial meningitis.…”

Section: Modulation Of Host Inflammatory Cytokinesmentioning

confidence: 99%

Treatment of bacterial meningitis: an update

Shin

Kim

2012

Expert Opinion on Pharmacotherapy

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Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.

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“…In a human whole blood model CyP was able to inhibit cytokine production induced not only through purified Neisseria meningitidis LPS, but also when cells were challenged by outer membrane vescicles or even live bacterial cells [29]. These results were confirmed later in a meningioma cell line and in an in vitro meningitis model infected with N. meningitidis [30]. Similarly, a porcine whole blood model showed that CyP suppressed cytokine expression induced by E. coli LPS.…”

Section: Biological Activity Of Cyanobacterial Lpssmentioning

confidence: 67%

Lipopolysaccharides in Cyanobacteria: A Brief Overview

Gemma¹,

Molteni²,

Rossetti³

2016

AiM

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Cyanobacteria are an interesting group of photosynthetic prokaryotes with a great potential in drug discovery and scientific research. Due to their high degree of diversification, they have been able to adapt to almost all ecological niches. Similarly to Gram-negative bacteria, cyanobacterial cell wall contains Lipopolysaccharides (LPSs) in the outer membrane layer. LPSs are molecules that possess the ability to elicit an innate immune response via Toll-like receptor 4 (TLR-4) activation. Cyanobacterial LPSs have been studied to a minor extent compared to Gram-negative bacterial LPSs. However, available data revealed important differences between the LPSs of these two groups of organisms, both in term of structure and biological activity. This review summarizes the current knowledge about cyanobacterial LPSs, highlighting their peculiarity and their potentiality compared to more characterized bacterial LPSs.

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Coadministration of the cyanobacterial lipopolysaccharide antagonist CyP with antibiotic inhibits cytokine production by an in vitro meningitis model infected with Neisseria meningitidis

Cited by 9 publications

References 37 publications

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Treatment of bacterial meningitis: an update

Lipopolysaccharides in Cyanobacteria: A Brief Overview

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