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African Plant-Based Natural Products with Antivirulence Activities to the Rescue of Antibiotics.

ABSTRACT: The worldwide emergence of antibiotic-resistant bacteria and the thread of widespread superbug infections have led researchers to constantly look for novel effective antimicrobial agents. Within the past two decades, there has been an increase in studies attempting to discover molecules with innovative properties against pathogenic bacteria, notably by disrupting mechanisms of bacterial virulence and/or biofilm formation which are both regulated by the cell-to-cell communication mechanism called 'quorum sensing' (QS). Certainly, targeting the virulence of bacteria and their capacity to form biofilms, without affecting their viability, may contribute to reduce their pathogenicity, allowing sufficient time for an immune response to infection and a reduction in the use of antibiotics. African plants, through their huge biodiversity, present a considerable reservoir of secondary metabolites with a very broad spectrum of biological activities, a potential source of natural products targeting such non-microbicidal mechanisms. The present paper aims to provide an overview on two main aspects: (i) succinct presentation of bacterial virulence and biofilm formation as well as their entanglement through QS mechanisms and (ii) detailed reports on African plant extracts and isolated compounds with antivirulence properties against particular pathogenic bacteria.

SUBMITTER: Mahavy CE

PROVIDER: S-EPMC7699609 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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African Plant-Based Natural Products with Antivirulence Activities to the Rescue of Antibiotics.

Mahavy Christian Emmanuel CE Duez Pierre P ElJaziri Mondher M Rasamiravaka Tsiry T

Antibiotics (Basel, Switzerland) 20201119 11

The worldwide emergence of antibiotic-resistant bacteria and the thread of widespread superbug infections have led researchers to constantly look for novel effective antimicrobial agents. Within the past two decades, there has been an increase in studies attempting to discover molecules with innovative properties against pathogenic bacteria, notably by disrupting mechanisms of bacterial virulence and/or biofilm formation which are both regulated by the cell-to-cell communication mechanism called ...[more]

PMID: 33228261

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Project description:Cyanobacteria are photosynthetic microorganisms that colonize diverse environments worldwide, ranging from ocean to freshwaters, soils, and extreme environments. Their adaptation capacities and the diversity of natural products that they synthesize, support cyanobacterial success in colonization of their respective ecological niches. Although cyanobacteria are well-known for their toxin production and their relative deleterious consequences, they also produce a large variety of molecules that exhibit beneficial properties with high potential in various fields (e.g., a synthetic analog of dolastatin 10 is used against Hodgkin's lymphoma). The present review focuses on the beneficial activities of cyanobacterial molecules described so far. Based on an analysis of 670 papers, it appears that more than 90 genera of cyanobacteria have been observed to produce compounds with potentially beneficial activities in which most of them belong to the orders Oscillatoriales, Nostocales, Chroococcales, and Synechococcales. The rest of the cyanobacterial orders (i.e., Pleurocapsales, Chroococcidiopsales, and Gloeobacterales) remain poorly explored in terms of their molecular diversity and relative bioactivity. The diverse cyanobacterial metabolites possessing beneficial bioactivities belong to 10 different chemical classes (alkaloids, depsipeptides, lipopeptides, macrolides/lactones, peptides, terpenes, polysaccharides, lipids, polyketides, and others) that exhibit 14 major kinds of bioactivity. However, no direct relationship between the chemical class and the respective bioactivity of these molecules has been demonstrated. We further selected and specifically described 47 molecule families according to their respective bioactivities and their potential uses in pharmacology, cosmetology, agriculture, or other specific fields of interest. With this up-to-date review, we attempt to present new perspectives for the rational discovery of novel cyanobacterial metabolites with beneficial bioactivity.

Project description:An antivirulence approach targets bacterial virulence rather than cell viability in the antibiotic approach that can readily lead to drug resistance. Opportunistic human pathogen Pseudomonas aeruginosa produces a variety of virulence factors, and biofilm cells of this bacterium are much more resistant to antibiotics than planktonic cells. To identify novel inorganic antivirulence compounds, the dual screenings of thirty-six metal ions were performed to identify that zinc ions and ZnO nanoparticle inhibited the pyocyanin production and biofilm formation in P. aeruginosa without affecting the growth of planktonic cells. Moreover, zinc ion and ZnO nanoparticle markedly reduced the production of 2-heptyl-3-hydroxy-4(1H)-quinolone and siderophore pyochelin, while increased the production of another sideropore pyoverdine and swarming motility. Further, zinc ion and ZnO nanoparticle clearly suppressed hemolytic activity in P. aeruginosa. Transcriptome analyses showed that ZnO nanoparticle induced zinc cation efflux pump czc operon, porin genes (oprD and opdT), and Pseudomonas type III repressor A ptrA, while repressed pyocyanin-related phz operon, which partially explains the phenotypic changes. Overall, ZnO nanoparticle is a potential candidate for use in an antivirulence approach against persistent P. aeruginosa infection. P. aeruginosa Genechip Genome Array (Affymetrix, P/N 900339) was used in order to study the cells after the addition of ZnO nanoparticles. DNA microarray analysis with one biological replicate was performed with an Affymetrix system. P. aeruginosa was inoculated in 25 ml of LB medium in 250 ml shaker flasks with overnight cultures (1 : 100 dilution). Cells were cultured for 5 h with shaking at 250 rpm with and without ZnO nanoparticles (1 mM). Before sample collection, RNase inhibitor (RNAlater, Ambion, TX, USA) was added, and the cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 s before centrifugation at 16,000 g for 2 min. The cell pellets were immediately frozen with dry ice and stored at –80°C. Total RNA was isolated using a Qiagen RNeasy mini Kit (Valencia, CA, USA).

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African Plant-Based Natural Products with Antivirulence Activities to the Rescue of Antibiotics.

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African Plant-Based Natural Products with Antivirulence Activities to the Rescue of Antibiotics.

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