A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

Abstract

Background: Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s' golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted. Objectives: This systematic review aims to evaluate reports on plants with significant antibacterial activities. Methods: Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: "plant," "antibacterial," "inhibitory concentration." Results: We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, while Cinnamomum verum, Rosmarinus vulgaris and Thymus vulgaris were the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally, Staphylococcus aureus was the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature. Conclusion: This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.

Keywords: antibacterial; antimicrobial; ethnopharmacology; medicinal plants; minimum inhibitory concentration.

FIGURE 1

Representation of inclusion and exclusion criteria, with corresponding results from the literature search used to construct the databases in Supplementary Material S1.

FIGURE 2

Number of publications per year in the search range from 1946 to September 3, 2019. Search keywords were “plant,” “inhibitory concentration” and “antibacterial.” Years discussed in this review (2012–2019) are highlighted in blue.

FIGURE 3

Most represented (A) families and (B) genera by number of species investigated for antibacterial activity in study range and (C) most studied plant species by number of publications, grouped by family.

FIGURE 4

The phylogenetic distribution of plant species tested for antibacterial activity were mapped on the family-level maximally resolved complete euphyllophyte phylogenetic tree according to Angiosperm Phylogeny Group IV (Gastauer and Meira Neto, 2017). Family names are only given for those genera reported in this study; major clades are indicated in different colors. The length of the gray bars surrounding the phylogeny are according to the number of species studied in each family, and the proportion of genera studied in each family is displayed in pie charts on each family node. A high resolution version of this figure for enlarged viewing is available as Supplementary Material S3.

FIGURE 5

(A) Distribution of plant species by country. Country designation was determined by location of plant material collection. (B) Distribution of top 10 families within countries for the top five countries according to the number of species investigated.

FIGURE 6

Categories of traditional medical use of antibacterial plant species.

FIGURE 7

(A) Plant tissues extracted for investigation for antibacterial activity. (B) Method of extraction used to create extracts.

FIGURE 8

Top 20 bacterial species by number of extracts tested.

FIGURE 9

Mean and standard deviation of minimum inhibitory concentration (MIC) of extracts in the top fifteen families, with significant differences in MIC values (μg/mL) for (A) all bacteria; (B) Gram-positive bacteria and (C) Gram-negative bacteria reported. Botanical family code: AN: Anacardiaceae, AO: Annonaceae, AP: Apiaceae, AC: Apocynaceae, AS: Asteraceae, CO: Combretaceae, EU: Euphorbiaceae, FA: Fabaceae, LM: Lamiaceae, LU: Lauraceae, MA: Malvaceae, MY: Myrtaceae, RB: Rubiaceae, RT: Rutaceae, ZI: Zingiberaceae. p values: blank: not significant, *: p < 0.05, **: p < 0.01, ***p < 0.001, ****p < 0.0001.

FIGURE 10

Minimum inhibitory concentration (MIC) of extracts reported by extraction type, with significant differences in MIC values for (A) all bacteria; (B) Gram-positive bacteria and (C) Gram-negative bacteria reported. Extraction code: AC: acetone, AQ: aqueous, CH: chloroform, DC: dichloromethane, EO: essential oil, ET: ethanol, EA: ethyl acetate, FR: fraction, HE: hexane, ME: methanol, NS: not specified, OT: other. p value: blank: not significant, *: p < 0.05, **: p < 0.01, ***p < 0.001, ****p < 0.0001.

FIGURE 11

Minimum inhibitory concentration (MIC) of extracts reported in the top ten plant tissues, with significant differences in MIC values for (A) all bacteria; (B) Gram-positive bacteria and (C) Gram-negative bacteria reported. Plant tissue code: AP: aerial part, BK: bark, FR: fruit, LF: leaf, RH: rhizome, RO: root, SD: seed, ST: stem, SB: stem bark, WH: whole plant, OT: other. p value: blank: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001.

FIGURE 12

MIC values of plant crude extracts with the lowest mean MIC values for (A) all bacteria; (B) Gram-positive bacteria and (C) Gram-negative bacteria reported.

FIGURE 13

MIC of plant essential oils with lowest mean MIC (µg/mL) for (A) all bacteria; (B) Gram-positive bacteria and (C) Gram-negative bacteria and lowest mean MIC (µL/mL) for (D) all bacteria; (E) Gram-positive bacteria and (F) Gram-negative bacteria. *: p < 0.05.

FIGURE 14

Select examples of plant species with antibacterial activity: (A) Curry leaf plant (Murraya koenigii, Rutaceae) is a tree native to the Indian subcontinent which showed one of the best mean MICs against Gram-positive bacteria, (B) Ginger (Zingiber officinale, Zingiberaceae) is an herb native to southeastern Asia and is one of the most active species. (C) Cashew (Anacardium occidentale, Anacardiaceae) is a tropical evergreen tree. It shows one of the best MIC values as a plant extract, and the Anacardiaceae family has the highest percentage of plants species studied for antibacterial activity, (D) Coriander (Coriandrum sativum, Apiaceae) is an herbaceous plant native to western Asia and southern Europe. Coriander seed EO shows one of the highest activities in the Apiaceae family, and this species is one the most investigated for antibacterial activity, (E) Rosemary (Rosmarinus officinalis, Lamiaceae) is a perennial herb native to the Mediterranean region. It is one of the five genera with the most species investigated for antibacterial activity. (F) Turmeric (Curcuma longa, Zingiberaceae) is an herbaceous plant native to south-east Asia. It is one of the five species that showed the best overall mean MIC values for Gram-negative bacteria.

FIGURE 15

Representative chemical structures of compounds discussed in this review; α-terpineol (1), carvacrol (2), thymol (3), α-terpinene (4), γ-terpinene (5), p-cymene (6), terpinen-4-ol (7), linalool (8), limonene (9), camphor (10), eucalyptol (11), α-pinene (12), borneol (13), carnosic acid (14), carnosol (15), rosmarinic acid (16), lupinifolin (17), glabridin (18), β-caryophyllene (19), ent-kaurenoic acid (20), β-sitosterol (21), epigallocatechin (22), germacrene D (23), quercetin (24), rhodomyrtone (25), ellagic acid (26), and eugenol (27).