Antimicrobial Plant Metabolites: Structural Diversity and Mechanism of Action

Abstract

Microbial infectious diseases continue to be one of the leading causes of morbidity and mortality. It has been estimated that microbial species comprise about 60% of the Earth's biomass. This, together with the fact that their genetic, metabolic and physiological diversity is extraordinary, makes them a major threat to the health and development of populations across the world. Widespread antibiotic resistance, the emergence of new pathogens in addition to the resurgence of old ones, and the lack of effective new therapeutics exacerbate the problems. Thus, the need to discover and develop new antimicrobial agents is critical to improve mankind's future health. Plant secondary metabolites (PSMs) offer particular promise in this sense. Plant Kingdom could be considered a rich source of the most diverse structures (e.g. there are more than 12,000 known alkaloids, more than 8,000 phenolic compounds and over 25,000 different terpenoids), many of which were proven to possess strong antimicrobial properties (e.g. thymol, eurabienol, etc.). In many instances, PSMs can be easily isolated from the plant matrix, either in pure state or in the form of mixtures of chemically related compounds. What is also important is that the development of bacterial resistance toward natural plant products (that are generally regarded as eco-friendly) has been thus far documented in a very limited number of cases (e.g. for reserpine). Having all of the mentioned advantages of PSMs as potential antimicrobials in mind, a major question arises: why is it that there are still no commercially available or commonly used antibiotics of plant origin? This review tries to give a critical answer to this question by considering potential mechanisms of antimicrobial action of PSMs (inhibition of cell wall or protein synthesis, inducing leakage from the cells by tampering with the function of the membranes, interfering with intermediary metabolisms or DNA/RNA synthesis/function), as well as their physical and chemical properties (e.g. hydrophilicity/lipophilicity, chemical stability). To address the possible synergistic/antagonistic effects between PSMs and with standard antibiotics, special attention has been given to the antimicrobial activity of PSM-mixtures (e.g. essential oils, plant extracts). Moreover, possible ways of overcoming some of PSMs molecular limitations in respect to their usage as potential antibiotics were also discussed (e.g. derivatization that would enable fine tuning of certain molecular characteristics).

Phytochemical screening and in vitro antimicrobial activity of Thymus lanceolatus Desf. from Algeria

“…Since microbial resistance to antibiotics reduces the possibility of treating infectious diseases and increases mortality [19] , the discovery of new antimicrobial agents is very important to improve mankind's future health [3] . In this report, we have evaluated the antimicrobial potency of T. lanceolatus extracts as potential source for new antimicrobial agents, since this species is not studied.…”

“…Then, Whatman No. 3 filter paper discs (6 mm of diameter), impregnated with 10 µL of extracts at 100 mg/mL (1 mg per disc), were placed on the surface of agar. Four discs were placed peripherally in each plate.…”

“…Including common infectious diseases, leading causes of morbidity and mortality [3] , which are directly responsible for 26% of annual deaths worldwide [4] , were also treated by those plants preparations since ancient times [5] . In modern medicine, the discovery of bioactive molecules from microbial origin and synthetic antimicrobial agents decreased the use of traditional plant preparations, especially in developed countries.…”

“…But in last decade, and besides their toxicities and side-effects [6] , it has become clear that current antimicrobial drugs are losing their effectiveness [7] , due to the emergence of resistance in pathogens to those antibiotics, which causes therapeutic failures and death of individuals [8] . Therefore, there is a continuing need to search for new antibiotics [3,7] . Since plant-derived antibacterials are always a source of novel therapeutics [9] , many researchers in field of ethnopharmacology have concentrated in studies of those compounds in the past few decades [5] on a promising and wealthy source for safe and effective new antimicrobial agents.…”

The re-emergence of natural products for drug discovery in the genomics era

“…Alternatively, other natural products from different sources could be tested. These could include microbial products of activated cryptic pathways (see elsewhere in this review) or secondary metabolites from plants [207][208][209][210][211][212] , endophytic fungi 213 , or marine sources 214 .…”