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.

Keywords: African plants; Escherichia; Pseudomonas; Ralstonia; Staphylococcus; antivirulence; biofilm; natural compounds; quorum sensing.

Figure 1

Schematic representation of bacterial invasion processes (A) P. aeruginosa, (B) E. coli, and (C) S. aureus. Bacterial dissemination is done thanks to active and/or passive motilities (swimming, swarming, twitching, gliding, sliding, and darting). In presence of appropriate surfaces and environment, the invasion is initiated by adhesion steps and microcolony formation which lead to the development of mature biofilms in four major steps (adhesion, microcolonies development, biofilm maturation, and dispersion). Under modulation by QS, the bacterial community deploys an arsenal of virulence factors (pyocyanin, heat labile (LT) and heat stable (ST)-enterotoxin, hemolysins, and leukotoxins) that undermine nearby cells (including immune defense cells) and stimulate the production of exogenous biofilm matrix for protection purposes.

Figure 2

Model of antibiotherapy combined with an antivirulence agent. (A) Schematic representation of bacterial invasion processes. (B) Scenario presenting the use of antibiotherapy alone and the difficulty of immune defense cells to clear biofilm-encapsulated bacteria even at high doses of antibiotic (e.g., four to 100-fold MICs [82,83]). (C) Scenario presenting the simultaneous use of antibiotic and antivirulence agents; antibiotics at MICs kill a majority of bacteria gathered inside an unstructured biofilm which can be easily cleared by immune defense cells.