Small molecules aimed at type III secretion systems to inhibit bacterial virulence

Tsou, Lun K.; Dossa, Paul D.; Hang, Howard C.

doi:10.1039/c2md20213a

Cited by 29 publications

(20 citation statements)

References 69 publications

(163 reference statements)

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“…The TTSS is a macromolecular complex essential for causing disease on susceptible plants. Through the TTSS, bacteria directly inject into the cytosol of host cells several pathogenicity and virulence effector proteins [ 5 ] .…”

Section: Introductionmentioning

confidence: 99%

Global Analysis of Type Three Secretion System and Quorum Sensing Inhibition of Pseudomonas savastanoi by Polyphenols Extracts from Vegetable Residues

et al. 2016

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Protection of plants against bacterial diseases still mainly relies on the use of chemical pesticides, which in Europe correspond essentially to copper-based compounds. However, recently plant diseases control is oriented towards a rational use of molecules and extracts, generally with natural origin, with lower intrinsic toxicity and a reduced negative environmental impact. In this work, polyphenolic extracts from vegetable no food/feed residues of typical Mediterranean crops, as Olea europaea, Cynara scolymus, and Vitis vinifera were obtained and their inhibitory activity on the Type Three Secretion System (TTSS) and the Quorum Sensing (QS) of the Gram-negative phytopathogenic bacterium Pseudomonas savastanoi pv. nerii strain Psn23 was assessed. Extract from green tea (Camellia sinensis) was used as a positive control. Collectively, the data obtained through gfp-promoter fusion system and real-time PCR show that all the polyphenolic extracts here studied have a high inhibitory activity on both the TTSS and QS of Psn23, without any depressing effect on bacterial viability. Extracts from green tea and grape seeds were shown to be the most active. Such activity was confirmed in planta by a strong reduction in the ability of Psn23 to develop hyperplastic galls on explants from adult oleander plants, as well as to elicit hypersensitive response on tobacco. By using a newly developed Congo red assay and an ELISA test, we demonstrated that the TTSS-targeted activity of these polyphenolic extracts also affects the TTSS pilus assembly. In consideration of the potential application of polyphenolic extracts in plant protection, the absence of any toxicity of these polyphenolic compounds was also assessed. A widely and evolutionary conserved molecular target such as Ca2+-ATPase, essential for the survival of any living organism, was used for the toxicity assessment.

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Section: Introductionmentioning

confidence: 99%

Global Analysis of Type Three Secretion System and Quorum Sensing Inhibition of Pseudomonas savastanoi by Polyphenols Extracts from Vegetable Residues

et al. 2016

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Section: Anti-virulence Strategies For P Aeruginosamentioning

confidence: 99%

“…P. aeruginosa T3SS is critical for delivery of toxins into host cells [31]; drug discovery has focused especially on targeting the T3SS effector ExoU/S, PscF/PcrV needle proteins, and the regulator ExsA [10,32]. The T3SS apparatus is well-conserved among pathogens, broadening the application of T3SS inhibitors to multiple pathogens [32] and polymicrobial infections. P. aeruginosa type II (T2SS) and type V secretion systems have been targeted to a lesser extent [33,34], though the similarities between T2SS and T3SS may reveal T2SS inhibitors incidentally [35].…”

Section: Anti-virulence Strategies For P Aeruginosamentioning

confidence: 99%

Considerations and caveats in anti-virulence drug development

Maura

Ballok

Rahme

2016

Current Opinion in Microbiology

127

110

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As antibiotic resistance remains a major public health threat, anti-virulence therapy research is gaining interest. Hundreds of potential anti-virulence compounds have been examined, but very few have made it to clinical trials and none have been approved. This review surveys the current anti-virulence research field with a focus on the highly resistant and deadly ESKAPE pathogens, especially Pseudomonas aeruginosa. We discuss timely considerations and caveats in anti-virulence drug development, including target identification, administration, preclinical development, and metrics for success in clinical trials. Development of a defined pipeline for anti-virulence agents, which differs in important ways from conventional antibiotics, is imperative for the future success of these critically needed drugs.

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“…1, 2 For example, the essential function of type III secretion systems (T3SSs) in Gram-negative bacteria virulence has highlighted these protein translocation organelles as prime targets for next-generation anti-infectives. 2–9 In the absence of T3SSs, bacterial pathogens such as Salmonella enterica serovar Typhimurium ( S. Typhimurium) cannot inject “effector” proteins into host cells to manipulate signaling pathways for invasion and intracellular replication. 6, 10 Beyond Salmonella , T3SSs are also crucial for the pathogenesis of other Gram-negative bacterial pathogens including Shigella , Pseudomonas , enteropathogenic Escherichia coli (EPEC), enterohemorrhagic Escherichia coli (EHEC), Chlamydia and Yersinia .…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-gallate inhibits bacterial virulence and invasion of host cells

Tsou

Yount

Hang

2017

Bioorganic & Medicinal Chemistry

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Increasing antibiotic resistance and beneficial effects of host microbiota has motivated the search for anti-infective agents that attenuate bacterial virulence rather than growth. For example, we discovered that specific flavonoids such as baicalein and quercetin from traditional medicinal plant extracts could attenuate Salmonella enterica serovar Typhimurium type III protein secretion and invasion of host cells. Here, we show epigallocatechin-3-gallate from green tea extracts also inhibits the activity of S. Typhimurium type III protein effectors and significantly reduces bacterial invasion into host cells. These results reveal additional dietary plant metabolites that can attenuate bacterial virulence and infection of host cells.

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Small molecules aimed at type III secretion systems to inhibit bacterial virulence

Abstract: The development of new anti-bacterial compounds presents a major challenge to modern medicine as bacterial strains resistant to traditional antibiotics are constantly emerging.

Cited by 29 publications

References 69 publications

Global Analysis of Type Three Secretion System and Quorum Sensing Inhibition of Pseudomonas savastanoi by Polyphenols Extracts from Vegetable Residues

Global Analysis of Type Three Secretion System and Quorum Sensing Inhibition of Pseudomonas savastanoi by Polyphenols Extracts from Vegetable Residues

Considerations and caveats in anti-virulence drug development

Epigallocatechin-3-gallate inhibits bacterial virulence and invasion of host cells

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