Synthesis and Evaluation of Troponoids as a New Class of Antibiotics

Cao, Feng; Orth, Cari; Donlin, Maureen J.; Adegboyega, Patrick A.; Meyers, Marvin J.; Murelli, Ryan P.; Elagawany, Mohamed; Elgendy, Bahaa; Tavis, John E.

doi:10.1021/acsomega.8b01754

Cited by 28 publications

(16 citation statements)

References 47 publications

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“…However, the tropolones and their derivatives have been mainly described as possessing biological activities, viz. insecticidal, antimicrobial, antiviral and antitumor 68 – 70 . 7-HT is considered to be the primary antimicrobial of P. donghuensis strains, being responsible both for antibacterial and antifungal properties of all P. donghuensis strains described so far 10 , 16 , 19 , 20 .…”

Section: Discussionmentioning

confidence: 99%

The carbon source-dependent pattern of antimicrobial activity and gene expression in Pseudomonas donghuensis P482

Matuszewska

Maciag

Rajewska

et al. 2021

Sci Rep

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Pseudomonas donghuensis P482 is a tomato rhizosphere isolate with the ability to inhibit growth of bacterial and fungal plant pathogens. Herein, we analysed the impact of the carbon source on the antibacterial activity of P482 and expression of the selected genes of three genomic regions in the P482 genome. These regions are involved in the synthesis of pyoverdine, 7-hydroxytropolone (7-HT) and an unknown compound (“cluster 17”) and are responsible for the antimicrobial activity of P482. We showed that the P482 mutants, defective in these regions, show variations and contrasting patterns of growth inhibition of the target pathogen under given nutritional conditions (with glucose or glycerol as a carbon source). We also selected and validated the reference genes for gene expression studies in P. donghuensis P482. Amongst ten candidate genes, we found gyrB, rpoD and mrdA the most stably expressed. Using selected reference genes in RT-qPCR, we assessed the expression of the genes of interest under minimal medium conditions with glucose or glycerol as carbon sources. Glycerol was shown to negatively affect the expression of genes necessary for 7-HT synthesis. The significance of this finding in the light of the role of nutrient (carbon) availability in biological plant protection is discussed.

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Section: Discussionmentioning

confidence: 99%

The carbon source-dependent pattern of antimicrobial activity and gene expression in Pseudomonas donghuensis P482

Matuszewska

Maciag

Rajewska

et al. 2021

Sci Rep

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“…In particular, the aforementioned excellent metalloenzyme-inhibiting capacity has been the basis for the development of potent inhibitors of various therapeutically important enzymes (Berkowitz et al, 2018). For instance, the chemically synthesized 4-Br-7HT is a potent inhibitor of multidrug resistant Acinetobacter baumanni (Cao et al, 2018). However, 7HT is currently produced only chemically by persulphate oxidation of tropolone, but it requires further purification to separate it from the byproducts 5HT, and 3,7-and 4,7dyhydroxytropolones (Nozoe et al, 1953;Kirst et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

7‐hydroxytropolone is the main metabolite responsible for the fungal antagonism of Pseudomonas donghuensis strain SVBP6

Muzio

Agaras

Masi

et al. 2020

Environmental Microbiology

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Summary Pseudomonas donghuensis strain SVBP6, an isolate from an agricultural plot in Argentina, displays a broad‐spectrum and diffusible antifungal activity, which requires a functional gacS gene but could not be ascribed yet to known secondary metabolites typical of Pseudomonas biocontrol species. Here, we report that Tn5 mutagenesis allowed the identification of a gene cluster involved in both the fungal antagonism and the production of a soluble tropolonoid compound. The ethyl acetate extract from culture supernatant showed a dose‐dependent inhibitory effect against the phytopathogenic fungus Macrophomina phaseolina. The main compound present in the organic extract was identified by spectroscopic and X‐ray analyses as 7‐hydroxytropolone (7HT). Its structure and tautomerism was confirmed by preparing the two key derivatives 2,3‐dimethoxy‐ and 2,7‐dimethoxy‐tropone. 7HT, but not 2,3‐ or 2,7‐dimethoxy‐tropone, mimicked the fungal inhibitory activity of the ethyl acetate extract from culture supernatant. The activity of 7HT, as well as its production, was barely affected by the presence of up to 50 μM added iron (Fe+2). To summarize, P. donghuensis SVBP6 produces 7HT under the positive control of the Gac‐Rsm cascade and is the main active metabolite responsible for the broad‐spectrum inhibition of different phytopathogenic fungi.

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“…However, the tropolones and their derivatives have been mainly described as possessing biological activities, viz. insecticidal, antimicrobial, antiviral and antitumor [65]- [67]. 7-…”

Section: Siderophore Biosynthesis As An Important But Not the Only Pamentioning

confidence: 99%

“…However, the tropolones and their derivatives have been mainly described as possessing biological activities, viz. insecticidal, antimicrobial, antiviral and antitumor [65]- [67]. 7-HT is considered to be the major antimicrobial of P. donghuensis strains, being responsible both for antibacterial and antifungal properties of all P. donghuensis strains described so far [10], [16], [19], [20].…”

Section: Siderophore Biosynthesis As An Important But Not the Only Pamentioning

confidence: 99%

Necessity requires no decision: carbon source-dependent pattern of antimicrobial activity and gene expression in Pseudomonas donghuensis P482

Matuszewska

Maciag

Rajewska

et al. 2021

Preprint

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Pseudomonas donghuensis P482 is a tomato rhizosphere isolate with the ability to inhibit growth of bacterial and fungal plant pathogens. Herein, we analysed the impact of the carbon source on the antibacterial activity of P482 and expression of the selected genes of three genomic regions in the P482 genome. These regions are involved in the synthesis of pyoverdine, 7‑hydroxytropolone (7-HT) and an unknown compound (“cluster 17”) and are responsible for antimicrobial activity of P482. We showed that the P482 mutants, defective in these regions, show variations and contrasting patterns of growth inhibition of the target pathogen under given nutritional conditions (with glucose or glycerol as a carbon source). We also selected and validated the reference genes for gene expression studies in P. donghuensis P482. Amongst ten candidate genes, we found gyrB, rpoD and mrdA the most stably expressed. Using selected reference genes in RT-qPCR, we assessed the expression of the genes of interest under minimal medium conditions with glucose or glycerol as carbon sources. Glycerol was shown to negatively affect the expression of genes necessary for 7-HT synthesis. The significance of this finding in the light of the role of nutrient (carbon) availability in biological plant protection is discussed.

show abstract

Synthesis and Evaluation of Troponoids as a New Class of Antibiotics

Cited by 28 publications

References 47 publications

The carbon source-dependent pattern of antimicrobial activity and gene expression in Pseudomonas donghuensis P482

The carbon source-dependent pattern of antimicrobial activity and gene expression in Pseudomonas donghuensis P482

7‐hydroxytropolone is the main metabolite responsible for the fungal antagonism of Pseudomonas donghuensis strain SVBP6

Necessity requires no decision: carbon source-dependent pattern of antimicrobial activity and gene expression in Pseudomonas donghuensis P482

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