Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids

Abstract

Flavonoids are among the most abundant natural bioactive compounds produced by plants. Many different activities have been reported for these secondary metabolites against numerous cells and systems. One of the most interesting is certainly the antimicrobial, which is stimulated through various molecular mechanisms. In fact, flavonoids are effective both in directly damaging the envelope of Gram-negative and Gram-positive bacteria but also by acting toward specific molecular targets essential for the survival of these microorganisms. The purpose of this paper is to present an overview of the most interesting results obtained in the research focused on the study of the interactions between flavonoids and bacterial proteins. Despite the great structural heterogeneity of these plant metabolites, it is interesting to observe that many flavonoids affect the same cellular pathways. Furthermore, it is evident that some of these compounds interact with more than one target, producing multiple effects. Taken together, the reported data demonstrate the great potential of flavonoids in developing innovative systems, which can help address the increasingly serious problem of antibiotic resistance.

Evaluation of Antibacterial Activity of Essential Oils of Melaleuca cajuputi Powell

“…Some compounds aim for the efflux mechanisms in Gram negative bacteria to regulate drug resistance. 22 In this study, we determined the antibacterial activities of essential oils of M. cajuputi against Gram positive (S. aureus, S. pyogenes, and MRSA) and Gram negative (K. pneumoniae and E. coli) bacteria using the disc diffusion and MIC assays. The results revealed that the essential oils of M. cajuputi intensively inhibited Gram positive bacteria compared to Gram negative bacteria, wherein the inhibition zones against Gram positive bacteria were greater than those in Gram negative bacteria.…”

Chemistry of Protein-Phenolic Interactions Toward the Microbiota and Microbial Infections

“…The microbial proteins affected by phenolic compounds belong to membrane (efflux system, cell envelope metabolism, and ATP synthase system), anabolic and catabolic reactions, pathogenic and antibioticresistance mechanisms, such as toxins and virulence factors transporters and antibiotic-inactivating enzymes, virulence factors, biofilm, and DNA metabolisms. Bacterial cell membrane is a complex system that plays roles as barrier between outside and inside of the cell, regulator of the osmotic, energy, and lipid systems, as well as cell wall maintenance (104). The major antibiotics, including penicillins, cephalosporins, and polymixins, target the bacterial membrane and cell wall, thus disrupting their functions and leading to bacterial death.…”

Dermal Drug Delivery of Phytochemicals with Phenolic Structure via Lipid-Based Nanotechnologies

“…For example, the flavonoids kaempferol, chrysin, quercetin, baicalein, luteolin, epigallocatechin gallate, gallocatechin, theaflavin, and theaflavin gallate, when in contact with the bacterial cell membrane, decrease its fluidity, while the isoflavonoids puerarin, ononin, daidzein, genistein, and the stilbene resveratrol have shown the opposite effect [90,91]. Destabilitization of the bacterial cell membranes could also result from phenolics stepping into reaction with enzymes responsible for cell membrane stability and integrity [68,94]. In addition, some phenolic acids (caffeic and gallic acids) acidify the bacterial membrane, leading to its disruption and changes in permeability and ion transport [95].…”

“…In general, the biologically active aglycons of phenolic compounds possess a structure rich in reactive functional groups, multiple phenolic groups, carbonyl groups (e.g., xanthones, anthraquinones, most flavonoids), free or esterified carboxylic groups (phenolic acids), among others. They easily step into hydrogen bonding with other biomolecules (nucleotides, proteins, including adhesins and receptors, enzymes as DNA/RNA polymerases and topoisomerases, transcriptases, proteases, and many others) [94,98,99] or complexation with metal ions (iron ions) [100] that are essential for the infectious cycle of pathogenic bacteria and viruses (adhesion, entry, replication and spread) [84,101]. This is a wideranging and nonspecific complex of potential interactions of phenolics that has led many researchers to understand their antiviral and antibacterial properties.…”