The New Antibacterial Properties of the Plants: Quo vadis Studies of Anti-virulence Phytochemicals?

Abstract

The recent increase in bacterial resistance to antibiotics has motivated the resurgence of the study of natural antimicrobial products. For centuries, plants have been recognized for their bactericidal properties. However, in the last two decades, it has been reported that several plant derived metabolites at growth subinhibitory concentrations also tend to have anti-virulence properties, since they reduce the expression of factors that cause damage and the establishment of pathogenic bacteria. In this area of study, plants have been positioned as one of the main natural sources of anti-virulence molecules, but only a small portion of the plant species that exist have been investigated. Also, anti-virulence studies have been primarily focused on analyzing the ability of extracts and compounds to inhibit quorum sensing and biofilms formation in vitro. This mini-review discusses the current panorama, the trends in the study of anti-virulence phytochemicals, as well as their potential for the development of antibacterial therapies.

Keywords: adjuvants; anti-virulence; antimicrobial phytochemicals; quorum sensing; virulence factors.

FIGURE 1

Schematic representation of the current status of antimicrobial strategies: “The world of the inhibitory”. The tip of the iceberg represents the bactericidal compounds that have been discovered, while the light of the beacon searches for current strategies to prevent the “dusk” of this class of molecules. The resurgence of research in natural products, repurposing drugs for use as antibiotics, nanoparticles, chemical synthesis of new bactericides, as well as advances in computer science, omics, artificial intelligence, and synthetic biology are playing a relevant role in the development of new bactericidal compounds (Zakeri and Lu, 2013; Pushpakom et al., 2018; Li et al., 2019; Stokes et al., 2020). However, in this analogy the strategy of “shooting to kill,” allows some pathogenic microorganisms to live and generate resistance; in addition, in the “crossfire” beneficial microorganisms are eliminated. In the “world of the sub-inhibitor,” the number of bioactive molecules to be explored is greater, and the strategy is based on “disarming without killing,” in theory, will not induce resistance. At values below the minimum inhibitory concentration (MIC), the compounds exhibit different effects, among which are anti-virulence, and signal molecule activity, and they have hormetic and adjuvant effects (Cox et al., 2017). The term “anti-virulence agent” also includes peptides, enzymes, and antibodies. QS, quorum sensing; TS33, type 3 secretion system and TCS, two-component systems.