Licoflavonol is an inhibitor of the type three secretion system of Salmonella enterica serovar Typhimurium

Guo, Zhixing; Li, Xiaoli; Li, Jianfang; Yang, Xuefei; Zhou, Yuan; Chen, Lu; Shen, Yuemao

doi:10.1016/j.bbrc.2016.07.018

Cited by 32 publications

(28 citation statements)

References 35 publications

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“…Phenolic compounds involved in plant defense signaling have been reported to block the T3SS in P. aeruginosa via the GacS-GacA two-component signal transduction system 26 . Cytosporone B, a fungal metabolite, and analogues selectively block the secretion of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins, without significant toxicity against bacteria 27 and similar effects have been reported for prenylated plant flavonoids, of which licoflavonol proved to be the most promising compound 28 . It was recently reported that the T3SS of Y. pseudotuberculosis is effectively blocked by piericidin A1, a metabolite produced by a marine actinobacterium 29 .…”

Section: Discussionmentioning

confidence: 63%

Exploring resveratrol dimers as virulence blocking agents – Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa

Sundin

Zetterström

et al. 2020

Sci Rep

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Bacterial infections continue to threaten humankind and the rapid spread of antibiotic resistant bacteria is alarming. current antibiotics target essential bacterial processes and thereby apply a strong selective pressure on pathogenic and non-pathogenic bacteria alike. one alternative strategy is to block bacterial virulence systems that are essential for the ability to cause disease but not for general bacterial viability. We have previously show that the plant natural product (-)-hopeaphenol blocks the type iii secretion system (T3SS) in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. (-)-Hopeaphenol is a resveratrol tetramer and in the present study we explore various resveratrol dimers, including partial structures of (-)-hopeaphenol, as T3SS inhibitors. To allow rapid and efficient assessment of T3SS inhibition in P. aeruginosa, we developed a new screening method by using a green fluorescent protein reporter under the control of the ExoS promoter. Using a panel of assays we showed that compounds with a benzofuran core structure i.e. viniferifuran, dehydroampelopsin B, anigopreissin A, dehydro-δ-viniferin and resveratrol-piceatannol hybrid displayed significant to moderate activities towards the T3SS in Y. pseudotuberculosis and P. aeruginosa.

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Section: Discussionmentioning

confidence: 63%

Exploring resveratrol dimers as virulence blocking agents – Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa

Sundin

Zetterström

et al. 2020

Sci Rep

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“…[32][33][34] In addition, licoflavonol was shown to exhibit a strong inhibitory effect on the secretion and the transportation of SPI-1 effector proteins. 35 Although a large number of T3SS inhibitors have been reported, they have rarely been screened from natural plant extracts. In addition, the cost, limited source materials and unclear mechanisms of action of many synthetic drugs seriously restrict their development and practical application.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the type III secretion system by syringaldehyde protects mice from Salmonella enterica serovar Typhimurium

Chu

Yao

et al. 2019

J Cellular Molecular Medi

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The invasiveness of Salmonella enterica serovar Typhimurium ( S . Typhimurium) is closely associated with the Salmonella pathogenicity island (SPI)‐encoded type Ⅲ secretion system (T3SS), which can directly inject a series of effector proteins into eukaryotic cells to enable bacterial infection. In this study, syringaldehyde was identified as an effective inhibitor of the S . Typhimurium T3SS using an effector protein‐lactamase fusion reporter system. Syringaldehyde treatment could inhibit the expression of important effector proteins (SipA, SipB and SipC) at a concentration of 0.18 mM without affecting bacterial growth. Additionally, significant inhibition of bacterial invasion and cellular injury was observed following the syringaldehyde treatment in the co‐infection system of HeLa cells and S . Typhimurium. Furthermore, treatment with syringaldehyde provided systemic protection to mice infected with S . Typhimurium, reducing mortality (40.00%) and bacterial loads and relieving caecal damage and systemic inflammation. The results presented in this study indicate that syringaldehyde significantly affects T3SS activity and is a potential leading compound for treating S . Typhimurium infections.

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“…A novel prenylated flavonoid derivative was identified as a Salmonella T3SS inhibitor, shown to inhibit secretion of effectors from the SPI-1 T3SS variant. 110 The compound, licoflavonol, did not affect bacterial mobility or viability, both key properties of anti-virulence compounds. Guo et al (2016) showed that licoflavonol down-regulated transcription of sicA and invF, as well as reduced secretion of several T3S injectisome secreted effectors, mainly the translocon component SipC (SctB).…”

Section: Inhibitor Classes and Their Associated Mechanism Of Inhibitionmentioning

confidence: 96%

On the road to structure-based development of anti-virulence therapeutics targeting the type III secretion system injectisome

Lyons

Strynadka

2019

Med. Chem. Commun.

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Licoflavonol is an inhibitor of the type three secretion system of Salmonella enterica serovar Typhimurium

Cited by 32 publications

References 35 publications

Exploring resveratrol dimers as virulence blocking agents – Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa

Exploring resveratrol dimers as virulence blocking agents – Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa

Inhibition of the type III secretion system by syringaldehyde protects mice from Salmonella enterica serovar Typhimurium

On the road to structure-based development of anti-virulence therapeutics targeting the type III secretion system injectisome

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