Flavone Reduces the Production of Virulence Factors, Staphyloxanthin and α-Hemolysin, in Staphylococcus aureus

Lee, Jin-Hyung; Park, Joo-Hyeon; Cho, Moo Hwan

doi:10.1007/s00284-012-0229-x

Cited by 63 publications

(52 citation statements)

References 24 publications

(34 reference statements)

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“…Since many plant bacterial pathogens use type III secretion systems to cause disease and sense flavonoids 30 , it is possible that some of these compounds may have evolved as a consequence host-pathogen interactions. Moreover, flavonoids have also been reported to target other anti-infective properties such as expression of virulence genes 31,32 , toxin activity 33-35 , quorum sensing 36-39 and biofilm formation 40,41 in bacterial pathogens as well as attenuate destructive host inflammation 42-44 . Given the broad pharmacological activities of flavonoids, these plant metabolites may affect microbial virulence mechanisms, including type III protein secretion substrates shown here, in addition to host pathways for their anti-infective properties in vivo .…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

et al. 2016

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Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Amongst the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveals a previously unappreciated mechanism of action for anti-infective medicinal plants.

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Section: Discussionmentioning

confidence: 99%

Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

et al. 2016

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“…Indeed, in an in vitro enzyme assay, Cu, along with Zn and Fe, was shown to inhibit the kinase activity of SaeS [42], possibly competing with Mg in SaeS. Finally, the following molecules have been reported to inhibit the expression of the sae -operon or some members of Sae-regulon and have a potential to be a Sae inhibitor: florfenicol [55], corilagin [56], licochalcone A [57], thymol [57], the enoyl-acyl carrier protein reductase inhibitor AFN-1252 [58], cerulenin [59], subinhibitory concentration of linezolid [60], Manuka honey [61], and flavone [62]. …”

Section: Signalsmentioning

confidence: 99%

The SaeRS Two‐Component System of Staphylococcus aureus

Liu

Yeo

Bae

2016

Genes

173

195

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In the Gram-positive pathogenic bacterium Staphylococcus aureus, the SaeRS two-component system (TCS) plays a major role in controlling the production of over 20 virulence factors including hemolysins, leukocidins, superantigens, surface proteins, and proteases. The SaeRS TCS is composed of the sensor histidine kinase SaeS, response regulator SaeR, and two auxiliary proteins SaeP and SaeQ. Since its discovery in 1994, the sae locus has been studied extensively, and its contributions to staphylococcal virulence and pathogenesis have been well documented and understood; however, the molecular mechanism by which the SaeRS TCS receives and processes cognate signals is not. In this article, therefore, we review the literature focusing on the signaling mechanism and its interaction with other global regulators.

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“…Recently, we reported that a plant flavone (Lee et al 2012) and a bacterial signaling molecule indole (Lee et al 2013) reduced the production of staphyloxanthin and α-hemolysin.…”

Section: Introductionmentioning

confidence: 98%

Anti-biofilm, anti-hemolysis, and anti-virulence activities of black pepper, cananga, myrrh oils, and nerolidol against Staphylococcus aureus

Lee

Kim³

et al. 2014

Appl Microbiol Biotechnol

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The long-term usage of antibiotics has resulted in the evolution of multidrug-resistant bacteria. Unlike antibiotics, anti-virulence approaches target bacterial virulence without affecting cell viability, which may be less prone to develop drug resistance. Staphylococcus aureus is a major human pathogen that produces diverse virulence factors, such as α-toxin, which is hemolytic. Also, biofilm formation of S. aureus is one of the mechanisms of its drug resistance. In this study, anti-biofilm screening of 83 essential oils showed that black pepper, cananga, and myrrh oils and their common constituent cis-nerolidol at 0.01 % markedly inhibited S. aureus biofilm formation. Furthermore, the three essential oils and cis-nerolidol at below 0.005 % almost abolished the hemolytic activity of S. aureus. Transcriptional analyses showed that black pepper oil down-regulated the expressions of the α-toxin gene (hla), the nuclease genes, and the regulatory genes. In addition, black pepper, cananga, and myrrh oils and cis-nerolidol attenuated S. aureus virulence in the nematode Caenorhabditis elegans. This study is one of the most extensive on anti-virulence screening using diverse essential oils and provides comprehensive data on the subject. This finding implies other beneficial effects of essential oils and suggests that black pepper, cananga, and myrrh oils have potential use as anti-virulence strategies against persistent S. aureus infections.

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Flavone Reduces the Production of Virulence Factors, Staphyloxanthin and α-Hemolysin, in Staphylococcus aureus

Cited by 63 publications

References 24 publications

Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

The SaeRS Two‐Component System of Staphylococcus aureus

Anti-biofilm, anti-hemolysis, and anti-virulence activities of black pepper, cananga, myrrh oils, and nerolidol against Staphylococcus aureus

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