Tackling Antibiotic Resistance with Compounds of Natural Origin: A Comprehensive Review

Abstract

Drug-resistant bacteria pose a serious threat to human health worldwide. Current antibiotics are losing efficacy and new antimicrobial agents are urgently needed. Living organisms are an invaluable source of antimicrobial compounds. The antimicrobial activity of the most representative natural products of animal, bacterial, fungal and plant origin are reviewed in this paper. Their activity against drug-resistant bacteria, their mechanisms of action, the possible development of resistance against them, their role in current medicine and their future perspectives are discussed. Electronic databases such as PubMed, Scopus and ScienceDirect were used to search scientific contributions until September 2020, using relevant keywords. Natural compounds of heterogeneous origins have been shown to possess antimicrobial capabilities, including against antibiotic-resistant bacteria. The most commonly found mechanisms of antimicrobial action are related to protein biosynthesis and alteration of cell walls and membranes. Various natural compounds, especially phytochemicals, have shown synergistic capacity with antibiotics. There is little literature on the development of specific resistance mechanisms against natural antimicrobial compounds. New technologies such as -omics, network pharmacology and informatics have the potential to identify and characterize new natural antimicrobial compounds in the future. This knowledge may be useful for the development of future therapeutic strategies.

Keywords: antibacterial compound; antimicrobial resistance; future medicine; natural antimicrobial; natural origin; phytochemicals; polyphenols.

Figure 1

Leading causes of death in the world in 2016 (blue bars) and prognosis for antimicrobial resistance (AMR) related deaths in 2050 (red bar).

Figure 2

Approximate dates of discovery of new classes of antibiotics and identification of bacterial resistance.

Figure 3

The number of research articles available in PubMed by searching “Natural Antimicrobial” from 1998 to 2018. The red arrow represents a growing trend.

Figure 4

Main known molecular targets of antimicrobial NPs described in this review.

Figure 5

Antimicrobial resistance mechanisms and acquisition mechanisms in bacteria.