The Potential of Systems Biology to Discover Antibacterial Mechanisms of Plant Phenolics

Abstract

Drug resistance of bacterial pathogens is a growing problem that can be addressed through the discovery of compounds with novel mechanisms of antibacterial activity. Natural products, including plant phenolic compounds, are one source of diverse chemical structures that could inhibit bacteria through novel mechanisms. However, evaluating novel antibacterial mechanisms of action can be difficult and is uncommon in assessments of plant phenolic compounds. With systems biology approaches, though, antibacterial mechanisms can be assessed without the bias of target-directed bioassays to enable the discovery of novel mechanism(s) of action against drug resistant microorganisms. This review article summarizes the current knowledge of antibacterial mechanisms of action of plant phenolic compounds and discusses relevant methodology.

Keywords: antimicrobials; mechanism of action; membrane; metabolic processes; microbial structure.

Figure 1

Known binding sites of phenolic compounds and their antibacterial targets from crystal structure data. Quercetin was observed to bind to the Helicobacter pylori beta-hydroxyacyl-acyl carrier protein (HpFabZ) at two sites (A,B; PDB structure 3CF8), apigenin bound to HpFabZ at the same two sites (C,D; PDB structure 3CF9), and quercetin bound to the kinase APH(2″)-IVa in three locations [E,F,G; PDB structure 4DFU (formerly 3R82)]. Isolated black spheres represent water and isolated gray spheres represent chloride ions. The ligand is in ball-and-stick representation while the protein side chains in contact range are in stick representation. PDB, protein data bank. This figure was made with BALLView (Moll et al., 2006).

Figure 2

Antibacterial mechanisms of action summarized for (A) common antibiotic classes and (B) plant phenolic compounds (adapted from Helander et al., ; Kohanski et al., ; Brown et al., 2015). PBP, penicillin binding protein. Effects of exogenous magnesium were not tested on a Gram-positive organism, only a Gram-negative organism.