Keywords

1 Introduction

Infectious diseases are the second greatest cause of death worldwide, after cardiovascular disorders, with 13.3 million people dying each year, being a primary source of morbidity and mortality. Every year, 700,000 people die as a result of bacterial resistance to drugs among the two million people who are sick with several types of bacteria around the world (Adrizain et al. 2018). The number of multidrug-resistant bacterial strains is continuously increasing, as is the advent of bacteria that are less susceptible to antibiotics. The indiscriminate and inappropriate uses of antibiotics have hastened the establishment of drug-resistant bacteria. Furthermore, unsanitary circumstances and improper food handling contribute to the spread of antibiotic resistance. Nosocomial infections with highly resistant bacterial pathogens have developed from a combination of extremely susceptible patients, extensive and sustained antibiotic usage, and cross infection. Hospital-acquired illnesses that are resistant to antibiotics are costly to treat and difficult to eliminate. Drug-resistant bacteria are responsible for up to 60% of hospital-acquired illnesses worldwide. Therefore, a hunt for new antibacterial compounds from a variety of sources, including medicinal plant, has sparked in recent times.

Since the time plants evolved, their important and protective roles have been well known for the mankind. Plants have been known to have anti-infective properties due to the presence of secondary metabolites such as tannins, alkaloids, terpenoids, and flavonoids, since ancient times. An evolving effective demand of natural plant-based products day by day lays an emphasis on the different medicinal plants used traditionally and in modern medicine system. A great majority of modern medicines have their roots in ancient herbal traditions. There are a variety of natural plant compounds with antifungal, antibacterial, and antiprotozoal properties that can be utilized systemically or locally (Dias et al. 2012a, b; Savoia 2012). The remedies obtained from the plants have given an insight for various afflicting human disorders. Plants are known for the production of various chemicals that are diverse in structures and have been adequately well utilized for various purposes. The diverse chemical compounds that have been reported to be useful as raw materials have led to the discovery of drugs for chronic disorders (Yuan et al. 2016; Dias et al. 2012a, b; Bariş et al. 2006). The increasing demands of plants in the present scenario make the plants more superior to other living organisms present on earth. A majority of medications in clinical use today are derived from naturally occurring compounds, primarily secondary metabolites. Traditional medicine is used by majority of the people worldwide to maintain their health. The earliest records on Indian traditional medicine prescribed the uses of plants in treatment of various ailments with focus on herbal medicines. The demands of herbal-based medicines are at an alarming rate in both developed and underdeveloped countries due to their safety measures and reduced costs (Cragg and Newman 2001). The current chapter discusses recent advances in the field of plant extracts/phytochemicals, which are being investigated as antibacterial and antimicrobial agents. Plant-derived compounds with antibiofilm or anti-quorum sensing properties and the diverse mechanisms behind their actions are also reviewed.

2 Secondary Metabolites Acting as Antimicrobial Agent

The secondary metabolites are organic compounds that are indirectly involved in the developmental processes of the plants. Metabolites play an important role in protecting the plants and conferring color, flavor, aroma, texture, and plant defense against various biotic and abiotic agents (Molyneux et al. 2007). The plants with high secondary metabolites such as alkaloids, phenols, tannins, terpenoids, saponins, and flavonoids are reported to have enhanced medicinal properties (Singh and Kumaria 2020a; Edema and Alaga 2012). The growing demands of plant-based metabolites have given insights to the discovery and utilization of the bioactive metabolites in bio-therapeutic uses (Rao and Roja 2002). The research works carried out over the years imply their efficiency and effectiveness against multidrug-resistant bacteria in both planktonic and biofilm forms. However, some phytochemicals show limited solubility in aqueous media, which further limits their medical usefulness. The use of surfactants, nanoparticles, and polymers can serve as an effective delivery vehicle to overcome this constraint.

2.1 Phenolic Compounds

Phenolics are diverse groups of plant secondary metabolites that are considered as evolving natural biomolecules due to their known effective bioactive properties. They are aromatic compounds synthesized in plants through shikimate/phenylpropanoid pathway, which leads to the production of phenols and polyphenols (Randhir et al. 2004). Plant phenolics are known to have significant roles in growth, development, and reproduction and also play a defensive role against the various biotic and abiotic stresses such as UV, chitosan, cold, dark, nutrient deficiency (Lattanzio 2013; Nag and Kumaria 2018; Singh and Kumaria 2020b). Phenolics are reported to participate in defense role against the predators and help in the development of color at different developmental stages of plants (Bravo 1998; Alasalvar et al. 2001). The phenolics are not only predominant in plants but are also reported from the bacteria, fungi, and algae (Harborne 2013). Also, it has been reported that the phenolics exhibit various biological properties such as antimicrobial, antiallergenic, and antioxidant activity (Balachandran et al. 2021). Many different types of phenolic compounds are known to be synthesized in plants and have been reported to be localized in different plant parts and serve as the potential agents for the action of various chronic diseases such as cancer, cardiovascular disease, and diabetes. The phenolics are also know to eliminate the foodborne bacteria and reduce the formation of biofilm. Due to the various useful applications of phenolics, therefore, their interest toward the food industry has increased day by day (Takó et al. 2020; Zambrano et al. 2019; Gyawali and Ibrahim 2014; Del Rio et al. 2013).

The various phenolics such as cinnamic acid, caffeic acid, p-coumaric acid, catechol, ferulic acid, pyrogallol, and eugenol have been reported to be effective against viruses, bacteria, and fungi (Kumar and Pandey 2013). Caffeic acid has been reported to have antimicrobial potential, synergistic effects with antibiotics against Staphylococcus aureus, S. epidermidis, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas mirabilis, Escherichia coli, P. aeruginosa, Bacillus cereus, and Mycobacterium luteus (Santos et al. 2018; Loes et al. 2014; Cushnie and Lamb 2005). Caffeic and p-coumaric acid have been reported to have synergy with the conventional antibiotics such as ampicillin and amikacin and increase their effectiveness against various gram-positive and gram-negative bacterial pathogens (Hemaiswarya and Doble 2010).

Another investigation has shown that the caffeic acid has anti-staphylococcal action, with minimum inhibitory concentrations (MICs) ranging from 62.5 to 250 g/mL (Luís et al. 2014). Catechol (two-hydroxyl group) and pyrogallol (three-hydroxyl group) are hydroxylated phenols that show toxic effects on microorganisms. More hydroxylation of catechol results in high toxicity. Mechanisms of phenol toxicity to microbes have been shown through enzyme inhibition processes with the oxidized compounds’ interaction with sulfhydryl groups or nonspecific interaction with proteins (Ciocan and Bara 2007).

Catechin is a polyphenol that acts on different bacterial strains by producing the hydrogen peroxide or by modifying the microbial membrane permeability (Kumar et al. 2013). Gallic acid has additionally been proven to have antibacterial activity against S. aureus, S. epidermidis, E. coli, Shigella flexneri, Salmonella spp., P. aeruginosa, and A. baumannii with MICs ranging from 630 to 5000 g/mL (Fu et al. 2016). Gallic acid is proven to be more effective against Campylobacter jejuni and Campylobacter coli with MICs ranging from 15.63 to 250 g/mL, the mechanism being the loss of calcium ions (Sarjit et al. 2015). According to another research, gallic acid–conjugated gold nanoparticles have shown a much better antibacterial activity than gallic acid alone against the foodborne pathogens Sh. flexneri and Plesiomonas shigelloides (Randhawa et al. 2016).

2.2 Quinones

Quinones are aromatic (hexacyclic saturated) di-one or di-ketone compounds, ubiquitous and highly reactive in nature. They are derived from the oxidation of hydroquinones, namely, anthraquinones, benzoquinones, naphthoquinones, and polyquinones. The browning reaction seen in cut vegetables is due to the accumulation of quinones. This also forms the intermediates in the synthesis of melanin and provides basis for the formation of stable free radicals. Quinones are also found accumulating irreversibly with nucleophilic amino acids in protein, which lead to functional loss of the proteins. Quinones have a wide range of antimicrobial effects (Jali 2021; Balachandran et al. 2021; Liu et al. 2017; Jung et al. 2016; Jiang et al. 2007).

2.3 Flavonoids and Their Derivatives

Flavonoids are a large, low molecular weight, and structurally diverse group of natural bioactive products. They are hydroxylated diphenylpropanes (C6–C3–C6) in structural skeleton. The reported flavonoids differ in the degree of oxidation, which leads to the diverse flavonoid derivatives (Kumar and Pandey 2013). Diverse group of flavonoids such as flavonols (quercetin, kaempferol, and myricetin), flavanones (naringin), flavones (luteolin), chalcones (licochalcone A, licochalcone E), catechins, anthocyanin, and isoflavonoids (sophoraisoflavone A) have been reported in plants (Farhadi et al. 2019; Patra 2012).

Flavonoids and their derivatives are synthesized in plants in response to different microbial attack. According to the report of Kumar and Pandey (2013), flavonoids have been reported to be effective against the wide array of microorganisms in in vitro studies. Flavonols such as quercetin, myricetin, morin, galangin, entadanin, rutin, piliostigmol, and their derivatives are among the most important class of flavonoids that show potent antibacterial activities (Siriyong et al. 2017; Geoghegan et al. 2010). The catechins present in green tea, epigallocatechin gallate (EGCG), have been found to be active against B. cereus in nanomolar concentrations (Friedman et al. 2006). Antibacterial activities of EGCG alone and in combination with various antibiotics have been studied extensively against a variety of bacteria, including multidrug-resistant strains such methicillin-resistant S. aureus (MRSA; Steinmann et al. 2013). The addition of long alkyl chains to EGCG dramatically increased its in vitro activity against a variety of bacteria and fungi, particularly S. aureus (Matsumoto et al. 2012). Another study demonstrated the action of EGCG on E. coli’s outer membrane and reported that the substance interacted with the membrane at many sites (Nakayama et al. 2013). Polyphenon E is prominent in distinguishing at least five distinct catechins, wherein EGCG is the most abundant component reported which is widely used clinically (Clark and You 2006). Another flavanol with antibacterial potential is a flavin, which has been shown to work against a variety of bacteria, including A. baumannii, B. cereus, and Shigella spp. (Betts et al. 2017; Friedman et al. 2006).

Many studies have shown that flavonoids are responsible for the inhibition of biofilm formation by disrupting the quorum sensing (QS). Flavonoids appear to impair the interaction between acyl-homoserine lactones (signal molecules used by gram-negative bacteria) and their receptors. It has been reported that baicalein inhibits the cytoplasmic membrane-associated receptor TraR (Zeng et al. 2008; Qin et al. 2000). Quercetin is a well-known flavonoid with a wide range of biological activities that include antioxidant, antibacterial, anti-inflammatory, antiviral and anticancer properties (Wang et al. 2016). Quercetin has been demonstrated to suppress E. coli growth under in vitro conditions and to have antibacterial effect against S. aureus and K. pneumoniae (Ohemeng et al. 1993). Mirzoeva et al. (1997) demonstrated that quercetin and other flavonoids reduce the bacterial motility considerably. Quercetin’s antibacterial activity was boosted in vitro when it was coupled with different antibiotics (Sakharkar et al. 2009; Hirai et al. 2010) and also had synergistic effects when combined with sulfamethoxazole, rifampicin, and fusidic acid against methicillin-resistant S. aureus (MRSA) strains and clinical isolates (Sahyon et al. 2019; Kyaw and Lim 2012). By hindering QS, quercetin was found to have antibiofilm activity against K. pneumoniae, Pseudomonas aeruginosa, and Yersinia enterocolitica (Gopu et al. 2015). A more recent research has revealed that quercetin can boost the antibacterial action of metals, with silver nanoparticles made from polyphenol having more antibacterial activity as compared to quercetin or silver nitrate alone against gram-negative and gram-positive infections (Jain and Mehata 2017).

Kaempferol, another flavonol, is reported to have a wide range of biological and pharmacological properties. It is known to impede the growth and survival of antibiotic-resistant S. aureus by inhibiting the activity of the PriA helicase (SaPriA) and bacterial efflux pumps, hence improving antimicrobial effectiveness and blocking the growth and survival of antibiotic-resistant S. aureus (Brown et al. 2015; Huang et al. 2015).

2.4 Tannins

Tannins are polymer of phenolic substances and are found in almost all the plants. Tannins are divided into condensed and hydrolyzable tannins. Hydrolyzable tannins are gallic acid based and contain multiple esters of D-glucose. The condensed form of tannins is often called proanthocyanidins and is derived from flavonoid monomers. It has been reported that tannins may have formed by condensations of flavan derivatives or by polymerization of quinine (Ciocan and Bara 2007; Karou et al. 2007). Studies have reported that tannins can be toxic to bacteria, yeast, and fungi (Cowan 1999). Punicalagin suppressed violacein synthesis in Chromobacterium violaceum and swarming motility in Sa. typhimurium SL1344 (Li et al. 2014).

2.5 Alkaloids

Alkaloids are the diverse group of chemical organic nitrogen-containing heterocyclic compounds. They are one of the structurally diverse groups of the metabolites effectively used as therapeutically important plant substances. Based on their core chemical structure, alkaloids are grouped into indoles, isoquinolines, piperidine alkaloids, quinolines, etc. The in-depth research on alkaloids from different plants have revealed their potential to acquire the properties of natural antibiotic with a wide antibacterial spectrum with low propensity to make drug resistant. When co-administered with ciprofloxacin, piperine, a piperidine-type alkaloid produced from Piper nigrum and P. longum, decreased the growth of a mutant S. aureus and considerably reduced the MIC values for S. aureus (Khan et al. 2006). Piperine and gentamicin co-administration was found to be effective in the treatment of MRSA infections (Khameneh et al. 2015). Tomatidine is a steroidal alkaloid found in solanaceous plants such as tomato, potato, and eggplant that has been shown to have significant antibacterial action against S. aureus whether used alone or in combination with aminoglycosides (Jiang et al. 2016).

The quinolone alkaloid evocarpine, isolated from Fructus evodiae, was found to have significant antimicrobial action against MRSA (Pan et al. 2014). The steroidal alkaloid tomatidine was isolated from the tomato plant. It has a high vulnerability to MRSA, according to the findings (Chagnon et al. 2014). Two guanidine alkaloids were found from the Pterogyne nitens. These two guanidine alkaloids, galegine and pteridine, possessed high anti-MRSA activity. The presence of a side chain observed in guanidine alkaloids was thought to impart the antibacterial property (Coqueiro et al. 2014). Because of the significant implications and need for conventional therapy following antibiotic failure against MRSA, there has been a huge push to develop novel compounds that can slow the progression of bacterial infections and enhance patient quality of life. Isolation of 6-methoxydihydrosanguinarine (6-MS), 6-acetonylhydrosanguinarine, and dihydrosanguinarine from Hylomecon hylomeconoides paved the door for medication sensitivity against MRSA to be regained. These alkaloids prevent MRSA strains with MICs ranging from 1.95 to 250 ug/mL (Choi et al. 2010). Plant alkaloids’ capacity to intercalate DNA may explain their ability to inhibit MRSA activity. It has also been proposed that alkaloid components impede or degrade beta-lactamase action (Zoraghi et al. 2011). Plant alkaloids such as berberine (found in Berberis sp.) and piperine (found in Piper sp.) can interact with the bacterial cytoplasmic membrane, intercalate with DNA, and inhibit efflux pumps in S. aureus (Khan et al. 2006; Jennings and Ridler 1983).

Berberine is an isoquinoline-type alkaloid used in the treatment of dental infections. Several investigations utilizing a multispecies biofilm tooth model have showed the efficacy of berberine against oral streptococcal growth and certain endodontic pathogens (Dziedzic et al. 2015; Xie et al. 2012). Berberine has been demonstrated to improve the inhibitory activity of antibiotics against clinical multidrug-resistant isolates of methicillin- resistant S. aureus (MRSA) (Chu et al. 2016). Berberine was found to have antibacterial activity against Streptococcus agalactiae by disrupting the membrane and reducing protein and DNA production (Peng et al. 2015). Dusane et al. (2014) studied the effect of reserpine and piperine from P. nigrum against E. coli, which causes urinary tract infections in humans. Piperine improved the action of the antibiotics azithromycin and ciprofloxacin in dispersing biofilms by increasing their penetration into E. coli biofilms.

2.6 Terpenoids

Terpenoids are a wide class of chemicals produced by plants that have antibacterial properties. Several terpenes and their derivatives have been demonstrated to be effective defenses against herbivores and infections. Gram-positive bacteria are usually more sensitive to terpenes than gram-negative bacteria. Terpenes’ antibacterial action is closely linked to their lipophilic properties. Monoterpenes preferentially affect membrane structures by increasing fluidity and permeability, modifying protein architecture, and causing disruptions along the respiration chain. Togashi et al. (2010) studied the effects of linalool, geraniol, nerolidol, plaunotol, farnesol, geranylgeraniol, and phytol on the growth of S. aureus. Among all of the compounds examined, only farnesol and nerolidol, with MBC of 20 and 40 g/mL, demonstrated a significant antibacterial effect. Two diterpenoids, salvipisone and aethiopinone, were extracted from Salvia sclarea roots and tested as antibacterial and antibiofilm agents against gram-positive and gram-negative bacteria. These diterpenoids inhibited the growth of S. aureus, S. epidermidis, and Enterococcus faecalis at a concentration of 37.5 g/ml, and S. aureus and S. epidermidis pre-formed biofilms were disturbed by at least 85% (Rózalski et al. 2007). Chung et al. (2014) extracted and identified three known triterpenoids (amyrin, betulinic acid, and betulinaldehyde) from the bark of Callicarpa farinosa. These compounds were found to have antibacterial activity against MRSA and methicillin-sensitive S. aureus (MSSA) and could be used to combat antibiotic resistance in S. aureus. Dehydroabietic acid, a resin acid, is reported to be another terpene molecule with antibacterial action against S. aureus. Broniatowski et al. (2015) investigated the antimicrobial mechanism of two pentacyclic triterpenes, ursolic acid and amyrin, which are natural chemicals with broad antibacterial activity. The other well-known terpenoids are eugenol and cinnamaldehyde, which are found in the essential oils of a variety of plants and have been shown to be effective against a variety of infections. Eugenol has been reported to have a lot of bioactivity against MRSA and MSSA clinical strain biofilms. According to the findings of Yadav et al. (2015), eugenol inhibits biofilm formation, disrupts cell-to-cell communication, eradicates pre-existing biofilms, and kills bacteria in biofilms, and this is true for both MRSA and MSSA. Essential oils including thymol, carvacrol, eugenol, and vanillin demonstrated antibacterial action against E. coli O157:H7, Sa. typhimurium, and Listeria monocytogenes when mixed with soy sauce (Moon and Rhee 2016). Knezevic et al. (2016) tested the antibacterial activity of essential oils from Eucalyptus camaldulensis against multidrug-resistant (MDR) Acinetobacter baumannii wound isolates.

2.7 Sulfur-Containing Phytochemicals

Organosulfur compounds such as allicin, ajoene, sulfasalazine, and isothiocyanates have been shown to have antibacterial activity against a variety of bacteria, including MDR strains. Park et al. (2013) investigated the antibacterial efficacy of horseradish root isothiocyanates against oral microbes. Dias et al. (2012b) investigated the antibacterial activity of isothiocyanates in the presence of antibiotics such as gentamicin and vancomycin against both gram-positive and gram-negative bacteria. Garlic’s main component allicin has been found as having antibacterial activity against a wide range of microorganisms. Allicin was responsive to vancomycin-sensitive and vancomycin-resistant clinical isolates and standard strains of Enterococcus species (Jonkers et al. 1999). When compared to diallyl sulfide, allicin had the best anti-Helicobacter pylori action against three strains (O’Gara et al. 2000). According to a meta-analysis of clinical data, combining allicin with standard therapy promotes the eradication of H. pylori infections (Si et al. 2019). Allicin was proven to be active against Clostridium difficile and other commensal gut bacteria in a recent study, and there was no substantial synergy between allicin and conventional antibiotics (Roshan et al. 2017).

A list of plant secondary metabolites such as alkaloids, flavonoids, tannins, terpenes, quinines, resins, coumarins, organosulfur, terpenoids, phenols, lactones, benzoic acid, diarylheptanoid, phenolic acids, polyphenol, iridoid lactone, and sesquiterpene lactone with their reported antibacterial activities is shown in more details in Table 2.1.

Table 2.1 Plant secondary metabolites with their reported antibacterial activities
Full size table

3 Quorum Sensing (QS)

QS, as a mechanism of bacterial cell-to-cell chemical communication, plays a key role in pathogen biofilm development, antibiotic resistance, survival, proliferation, and toxin synthesis. Targeting quorum sensing has emerged as a viable technique for fighting against bacterial infections since it does not put any selection pressure on pathogens, making it unlikely to develop multidrug resistance. Quorum quenching phytochemicals may be a potential non-antibiotic therapy method for pathogenic bacteria by inhibiting bacterial communication and making them less virulent. Extracts and specific compounds from several fruits, herbs, and spices have been displayed to inhibit QS. Polyphenols, for example, are QS-inhibiting phytochemicals that can impact biofilm development in some bacteria, because their chemical structure is comparable to that of QS signals N-acyl-homoserine lactones (AHL) and/or their capability to degrade signal receptors (LuxR/LasR) (Santos et al. 2021; Hossain et al. 2017). Gamma-aminobutyric acid (GABA), which is generated by some plants, promotes lactonase (AttM) degradation of the OHC8HSL AHL signal in Agrobacterium tumefaciens, limiting the QS-dependent infection process. The extracts from the Annurca apple having various polyphenols, such as hydroxycinnamic acids, rutin, and epicatechin, revealed anti-quorum sensing (AQS) activity against Chromobacterium violaceum (Fratianni et al. 2013). Cinnamaldehyde and its derivatives have an impact on a range of QS-regulated activities, including biofilm formation in P. aeruginosa and AI-2-mediated QS in various Vibrio species (Brackman et al. 2008; Niu et al. 2006). Garlic extracts have been shown to suppress QS in P. aeruginosa, reducing biofilm formation and thereby aiding the bacteria’s clearance (Bjarnsholt et al. 2005). Similarly, vanilla extracts have been reported to hamper with QS in C. violaceum, suggesting that eating vanilla-flavored meals may be helpful (Choo et al. 2006). Many plants produce polyphenol chemicals with a gallic acid moiety, such as epigallocatechin gallate, ellagic acid, and tannic acid, which can particularly interfere with AHL-mediated signalling by preventing bacteria-to-bacterium transmission (Hao et al. 2021; Bouyahya et al. 2017; Slobodníková et al. 2016).

It was reported that in case of a clinically import ant strain, i.e., S. aureus, baicalein (5,6,7-trihydroxyflavone) was found to lower levels of enterotoxin A (SEA) and hemolysin (hla) (Chen et al. 2016). At sub-inhibitory concentrations (32 and 64 g/ml), baicalein treatment significantly reduced the expression of the quorum sensing regulators agrA, RNAll, and sarA and the expression of the ica gene.

Quercetin, a common flavonoid, interacts to the QS receptor protein LasR and inhibits its capacity to bind promoter regions of DNA, lowering total QS gene production. The presence of two hydroxyl groups in the flavone A ring is required for suppression of QS-related self-regulatory proteins in P. aeruginosa, according to structure–activity relationship (SAR) analyses of various flavonoids. Among the plant-derived pigments, zeaxanthin was tested for QS inhibitory action using two P. aeruginosa fluorescent monitor strains, lasB-gfp and rhlA-gfp. The levels of gene expression of lasB and rhlA were shown to decrease in a concentration-dependent way (Gökalsın et al. 2017). Quorum sensing is known to influence the expression of numerous virulence factors. Attenuating pathogenicity in bacteria through QS interference is predicted to result in disease control, especially where antibiotics are ineffective owing to the development of multidrug resistance.

4 Future Prospects

Nature provides a rich supply of bioactive substances that are readily available, inexpensive, and simple to extract with little risk to humans. Phytochemicals have emerged as a possible alternative to conventional antibacterial medicines. A majority of antimicrobial phytochemicals lack thorough structure–activity relationship (SAR) data, which has been done for many classes of microbial antibiotics. The variety in extraction procedures and antibacterial assays utilized is a key barrier for identifying new antibacterial compounds from plants. Depending on their ability to suppress the growth of microorganisms, different phytochemicals have different antimicrobial properties. They come in a variety of forms, each with improved efficacy against a variety of diseases and pathogens. Modern approaches have been employed with traditional ways for extracting phytochemicals to boost yield and productivity. The key barrier in the development of novel phytochemicals has been translating in vitro investigations into in vivo experiments and then into human clinical trials. The challenge is particularly difficult in the case of natural antimicrobial drugs/antibacterial phytochemicals, because a variety of parameters, such as tissue penetration, maximum plasma concentration, and bioavailability, might affect their activity. For example, phenolic natural compounds are easily glucuronidated by hepatic enzymes, which have a significant impact on tissue penetration and plasma levels. To boost phytochemical antibacterial activity, various nanoformulations can be developed using liposomes, dendrimers, micelles, and polymers. The development of new antimicrobial metabolites from medicinal plants is a promising approach to combating to human diseases’ increasing treatment resistance. Scientists have conducted studies on many plant families to identify antibacterial properties of phytochemicals, and experimental investigations to evaluate the biological activities of numerous plants should be conducted in the future. Another appealing application of phytochemicals is their potential in combination with other antibacterial products, which merits more investigation.

5 Conclusion

Plant-derived chemicals or herbal medicine offer a significant contribution to primary healthcare and have shown considerable promise in modern phytomedicine for a variety of diseases and ailments in today’s world. Scientists have looked to nature for solutions to the fast growth of bacterial resistance to conventional antibiotics. As a source of novel antimicrobials, plants offer a lot of promise. They are commonly available, inexpensive, and almost without negative effects. Numerous investigations have been conducted, and the medicinal potential of plant-derived substances has been established. Thousands of phytochemicals have been discovered all over the world that exhibit antibacterial, antifungal, and antiviral action against a variety of diseases. When used with antibiotics, the MIC values of the antibiotics are reduced, and synergistic effects are observed.

Phytochemicals, in general, damage the bacterial membrane, reduce some virulence factors such as enzymes and toxins, and hinder the production of bacterial biofilms. However, a lot of significant work needs to be done in vitro and in vivo to assure the identification of active and nontoxic antimicrobial phytochemicals. Antibacterial agents with a new mechanistic approach should be sought quickly to tackle the problems of antibiotic resistance.