Morin hydrate attenuates Staphylococcus aureus
 virulence by inhibiting the self-assembly of α-hemolysin

Wang, J.; Zhou, Xuan; Liu, S.; Li, G.; Shi, Lei; Dong, Jing; Li, W.; Niu, Xiaodi

doi:10.1111/jam.12743

Cited by 53 publications

(42 citation statements)

References 27 publications

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“…Previous studies found that S. aureus caused severe cell injury to A549 cells in co-culture systems; however, an Hla mutant strain didn't injure A549 cells in the same system (Wang et al 2015). These results showed that Hla has critical cytotoxicity for A549 cells.…”

Section: Imperatorin Protects A549 Epithelial Cells From Hla-mediatedmentioning

confidence: 56%

“…Hla has been demonstrated to be an essential factor that mediates injury and death of A549 epithelial cells (Wang et al 2015). A549 cells were cultured in minimum essential medium (MEM, Invitrogen) containing 4.5 mg/mL glucose (D-glucose monohydrate; Merck) and 10 % certified fetal calf serum (FCS, Bioind).…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

“…Previous studies have indicated that many natural products can affect the production of Hla by S. aureus and have therapeutic effects on S. aureus pneumonia in a mouse model (Qiu et al 2010(Qiu et al , 2011aWang et al 2015;Zhou et al 2015). Imperatorin (9-(3-Methylbut-2-enoxy)-7-furo[3, 2-g]chromen-7-one), a furocoumarin compound (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Imperatorin inhibits the expression of alpha-hemolysin in Staphylococcus aureus strain BAA-1717 (USA300)

Ouyang

Chen

Sun

et al. 2016

Antonie van Leeuwenhoek

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Both community-associated and hospital-acquired infections with methicillin-resistant Staphylococcus aureus (MRSA) have been increasingly reported around the world in the past 20 years. In 2006, the Centers for Disease Control and Prevention reported that 64 % of MRSA isolates were of the USA300 clonal type in infected patients in USA. The aim of our study was to estimate the in vitro effect of imperatorin on MRSA strain BAA-1717 (USA300). The effects of imperatorin on alpha-hemolysin (Hla) production, when strain BAA-1717 was co-cultured with sub-inhibitory concentrations of imperatorin, were analysed using susceptibility testing, hemolysis assays, western blotting and real-time PCR. Live/Dead analysis and cytotoxicity assays were employed to examine the protective effect of imperatorin against the strain BAA-1717-mediated injury of human alveolar epithelial cells (A549). The results showed that imperatorin has no anti-S. aureus activity at the tested concentrations in vitro. However, imperatorin can observably inhibit the production of Hla in culture supernatants and reduce the transcriptional levels of hla (the gene encoding Hla) and arg (the accessory gene regulator). Imperatorin prevented Hla-mediated A549 epithelial cell injury in a co-culture system. In conclusion, our results suggested that imperatorin has the potential to be developed as a new anti-virulence drug candidate for managing S. aureus infection.

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Section: Imperatorin Protects A549 Epithelial Cells From Hla-mediatedmentioning

confidence: 56%

Section: Cytotoxicity Assaymentioning

confidence: 99%

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Imperatorin inhibits the expression of alpha-hemolysin in Staphylococcus aureus strain BAA-1717 (USA300)

Ouyang

Chen

Sun

et al. 2016

Antonie van Leeuwenhoek

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“…21,[28][29][30] Qiu et al previously reported that baicalin, a kind of flavonoid, inhibited the cytolytic activity of alpha-hemolysin by blocking the assembly of the alpha-hemolysin monomer to a heptamer and also had a protective effect against S. aureus pneumonia in a mouse model. 21) In the present study, we determined whether baicalin inhibited the activity of ALH.…”

Section: Discussionmentioning

confidence: 99%

Indolo[3,2-b]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by Aeromonas sobria and Alpha-Hemolysin Produced by Staphylococcus aureus

Takahashi

Fujinami

Kuroda

et al. 2016

Biological & Pharmaceutical Bulletin

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In an attempt to discover inhibitory compounds against pore-forming toxins, some of the major toxins produced by bacteria, we herein examined the effects of four kinds of indolo[3,2-b]quinoline derivatives on hemolysis induced by the aerolysin-like hemolysin (ALH) of Aeromonas sobria and also by the alphahemolysin of Staphylococcus aureus. The results showed that hemolysis induced by ALH was significantly reduced by every derivative, while that induced by alpha-hemolysis was significantly reduced by three out of the four derivatives. However, the degrees of reduction induced by these derivatives were not uniform. Each derivative exhibited its own activity to inhibit the respective hemolysin. Compounds 1 and 2, which possessed the amino group bonding the naphthalene moiety at the C-11 position of indolo[3,2-b]quinoline, had strong inhibitory effects on the activity of ALH. Compound 4 which consisted of benzofuran and quinoline had strong inhibitory effects on the activity of alpha-hemolysin. These results indicated that the amino group bonding the naphthalene moiety of compounds 1 and 2 assisted in their ability to inhibit ALH activity, while the oxygen atom at the 10 position of compound 4 strengthened its interaction with alpha-hemolysin. These compounds also suppressed the hemolytic activity of the supernatant of A. sobria or A. hydrophila, suggesting that these compounds were effective at the site of infection of these bacteria.

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“…The minimal inhibitory concentrations (MICs) of diosmetin against S. aureus in TSB were determined using the broth microdilution method described in our previous study (Wang et al 2015b). The MICs were defined as the lowest concentrations that inhibited bacterial growth.…”

Section: Determination Of Minimal Inhibitory Concentrationsmentioning

confidence: 99%

Diosmetin inhibits the expression of alpha-hemolysin in Staphylococcus aureus

Shui

Zhou

et al. 2015

Antonie van Leeuwenhoek

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Staphylococcus aureus is a significant human pathogen that causes a wide range of diseases. Alpha-hemolysin (Hla), a pore-forming cytotoxin that is produced by most S. aureus strains, can cause tissue injury and plays a critical role in the virulence of this pathogen. In the present study, we discovered that diosmetin, a natural flavonoid that occurs primarily in citrus fruits and exhibits little anti-S. aureus activity, could diminish the production of Hla in culture supernatants in a concentration-dependent manner. The analysis of cytotoxicity in the co-culture system of S. aureus and A549 epithelial cells showed that such inhibition confers significant protection against S. aureus-mediated injury. Our results suggested that diosmetin has the potential to be a new anti-virulence drug for S. aureus infection, particularly for the targeting of Hla.

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Morin hydrate attenuates Staphylococcus aureus virulence by inhibiting the self-assembly of α-hemolysin

Abstract: These findings suggested that morin is a promising candidate for the development of anti-virulence therapeutic agents for the treatment of Staph. aureus infections.

Cited by 53 publications

References 27 publications

Imperatorin inhibits the expression of alpha-hemolysin in Staphylococcus aureus strain BAA-1717 (USA300)

Imperatorin inhibits the expression of alpha-hemolysin in Staphylococcus aureus strain BAA-1717 (USA300)

Indolo[3,2-<i>b</i>]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by <i>Aeromonas sobria</i> and Alpha-Hemolysin Produced by <i>Staphylococcus aureus</i>

Diosmetin inhibits the expression of alpha-hemolysin in Staphylococcus aureus

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