**3. Rhizospheric microorganisms: an overview**

The term rhizosphere was first used in 1904 by agronomist and plant physiologist Lorenz Hiltner to describe the interface between plant roots and the soil inhabited by a unique microbial community, which is influenced by the chemical release from plant roots [49]. In recent years, based on the relative proximity and influence to the root, the rhizosphere definition has been refined to include three zones: (i) endorhizosphere, which includes portions of the cortex and endoderm, where microorganisms and mineral ions occupy free space between cells (apoplastic space); (ii) rhizoplane, a middle zone adjacent to the root's epidermal cells and mucilage; and (iii) ectorhizosphere, which extends from the rhizoplane out into the bulk soil and is colonized by the microorganisms that are either free-living or non-symbionts [50, 51].


**77**

*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules…*

*Paris polyphylla* Diphenyl ethers

*amboinicus* Lour.

*Streptomyces* sp. *Kandelia candel* Eudesmene-type

*S. sundarbansensis Fucus* sp. Polyketides (2-hydroxy-

**Endophyte Host plant Compound Target strain Reference**

Hemiterpenoid compounds

*S. aureus* MRSA (ZR11)

*S. aureus* (ATCC 25923)

*E. coli* (ATCC 11229) *P. aeruginosa* (ATCC 27853) *B. subtilis* (ATCC

*S. typhi* (clinical) *S. mutans* (ATCC 25175)

*Enterococcus faecalis* VRE

6633)

*B. subtilis* (ATCC

*S. aureus* MRSA (ATCC 43300)

*C. albicans*

*S. epidermis* MRSA (ATCC 35984)

*S. aureus* MRSA (ATCC 25923)

*S. aureus* MRSA (ATCC 43300)

*S. aureus* MRSA (ATCC 49476) S.aureus MRSA (ATCC 33591)

*S. aureus* MRSA

25922) *K. pneumoniae* (ATCC 13883)

1-Acetyl-β-carboline *S. aureus* MSSA [46]

*E. coli* [43]

6633)

[38]

[39]

[41]

[42]

[44]

[45]

derivates

*Streptomyces* sp. *Kandelia candel* Indolosesquiterpenes *S. aureus* MRSA [40]

sesquiterpenes (kandenols)

one)

5-((6-hydroxy-4-oxo-4H-pyran-2-yl) methyl) -2- propylchroman-4

2-amino-3,4-dihydroxy-5-methoxybenzamide

(*Z*)-tridec-7-ene-1,2,13 tricarboxylic acid

Diketopiperazine *cyclo* (tryptophanyl-prolyl); chloramphenicol

Actinomycin-D *E. coli* (ATCC

*DOI: http://dx.doi.org/10.5772/intechopen.93598*

**Endophytic fungi**

*Athelia rolfsii Coleus* 

**Endophytic bacteria**

*Streptomyces* sp. *Dysophylla* 

*Streptomyces* sp. *Dracaena* 

*Streptomyces sp. Zingiber* 

*Microbispora* sp. *Vochysia* 

*stellata*

*cochinchinensis*

*spectabile*

*divergens*

*Phomopsis asparagi*


*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules… DOI: http://dx.doi.org/10.5772/intechopen.93598*

*Antimicrobial Resistance - A One Health Perspective*

*Panax notoginseng*

*Cinnamomum kanehirae*

*Laguncularia racemosa*

*Mangifera indica* 4-(2,4,7-trioxa-

**Endophyte Host plant Compound Target strain Reference**

bicyclo[4.1.0]heptan-3-yl) phenol (1)

(22E,24R)-stigmasta-5,7,22-trien-3-β-ol; Aspernolide F

Shikimic acid *S. aureus* [29]

Beauvericin MR *S. aureus* [30]

3-Hidroxypropionic acid *S. aureus* [31]

Helvolic acid *B. subtilis* (UBC

Gliotoxin *C. neoformans*

344)

MR *S. aureus* ATCC 33591

*S. aureus* MRSA (ATCC 33591)

*C. neoformans* (ATCC 90113)

(ATCC 90113)

*B. subtilis* (UBC

*S. aureus* (ATCC 43300)

*S. aureus* MRSA (ATCC 33591) *E. coli* (UBC 8161) *P. aeruginosa* (ATCC 27853) *C. albicans* (ATCC 90028)

(ATCC 43300)

344)

Spiroaspertrione A *S. aureus* MRSA [36]

Aspermerodione *S. aureus* MRSA

*E. coli*

*B. subtilis* (ATCC66333)

*S. typhi*

*B. subtilis* (MTCC 441)

*E. coli* (MTCC 443) *P. aeruginosa* (MTCC 424) *K. pneumonia* (MTCC 109) *C. albicans* (MTCC 227)

[32]

[33]

[34]

[35]

[37]

**Endophytic fungi**

*Trichoderma ovalisporum*

*Fusarium oxysporum*

*Diaporthe phaseolorum*

*Pestalotiopsis mangiferae*

*Xylaria* sp. *Anoectochilus* 

*Aspergillus terreus Carthamus* 

*Hypocrea virens Premna* 

*setaceus*

*lanatus*

*serratifolia* L.

*Hypericum perforatum*

*Hypericum perforatum*

**76**

*Aspergillus* sp. TJ23

*Aspergillus* sp. TJ23

*Antimicrobial Resistance - A One Health Perspective*


#### **Table 1.**

*Secondary metabolites produced by endophytic fungi and bacteria with antimicrobial activity (2010–2020).*

The rhizosphere is a complex and dynamic region, where bacteria (including Plant Growth-Promoting Rhizobacteria—PGPR), fungi (including Arbuscular Mycorrhizal Fungi – AMF), oomycetes, viruses and archaea are attracted by chemical compounds (sugars, proteins, fatty acids, organics acids, vitamins, and other cellular components) released in the vicinity of the plant roots [16, 52, 53]. These rhizodeposits are used as carbon sources by microorganisms and represent an essential source of carbon allocated to the roots and available to plants through photosynthesis [54].

Rhizodeposits also contain secondary metabolites (flavonoids, antimicrobials and others) involved in establishing symbiosis or repelling plant pathogens and pests [55, 56].

The establishment of the symbiotic plant-PGPR interaction in the rhizosphere can favor the plant growth through direct and indirect mechanisms. The first one includes the fixation of atmospheric nitrogen [57], phosphate solubilization [58] or any other process capable of supplying the plant with some of its previously unavailable nutrients. Many PGPRs also produce phytohormones, such as auxins (Indole-3-acetic acid) and cytokinin, which exert strong effects on root and shoot growth, respectively [59–61]. The indirect mechanisms of plant growth prevent the deleterious effects of pathogens and include competition for nutrients and niches, induction of systemic resistance (Jasmonic acid (JA), and ethylene), and lytic

**79**

**Figure 2.**

**Rhizospheric microorganism**

**Fungi**

*Penicillium* 

12676

**Bacteria**

*simplicissimum MA-332*

*Aspergillus niger* MTCC

*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules…*

phore, bacteriocins and antibiotics production [62] (**Figure 2**).

enzymes (chitinase, pectinase, cellulase, glucanase, protease, xylanase), sidero-

The phyla of PGPR commonly found in the rhizosphere are Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes; among the main genera, *Burkholderia*, *Azotobacter, Pseudomonas*, *Bacillus, Methylobacterium*, *Serratia*, *Streptomyces*,

*Azospirillum*, *Herbaspirillum* and *Rhizobium* can be mentioned [63, 64]. The latter can establish an effective symbiotic relationship with plant species of the Leguminosae

*Basic scheme of the rhizospheric space showing saprophytic and symbiotic bacteria and fungi, including* 

*Aspergillus awamori* F12 Emodin *S. aureus* [75]

**Compound/extracts Target strains Reference**

Penicisimpins A–C *E. coli* [76]

Ethanol and ethyl acetate extracts *Streptococcus mutans*

*B. subtilis*

*Micrococcus luteus P. aeruginosa*

[77]

[78]

(MTCC497)

*Listeria monocytogenes* (PTCC 1163)

*B. cereus* (PTCC 1015) *S. aureus* MRSA (ATCC 1912) *Enterococcus* VRE

*S. aureus* (MTCC7443) *E. coli* (MTCC40) *C. albicans* (MTCC227) *Candida glabrata* (MTCC3814)

*DOI: http://dx.doi.org/10.5772/intechopen.93598*

*arbuscular mycorrhizal fungi. Adapted from [16].*

*Bacillus pumilus* Bacteriocin-like inhibitory substance (BLIS)

*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules… DOI: http://dx.doi.org/10.5772/intechopen.93598*

enzymes (chitinase, pectinase, cellulase, glucanase, protease, xylanase), siderophore, bacteriocins and antibiotics production [62] (**Figure 2**).

The phyla of PGPR commonly found in the rhizosphere are Actinobacteria, Firmicutes, Proteobacteria and Bacteroidetes; among the main genera, *Burkholderia*, *Azotobacter, Pseudomonas*, *Bacillus, Methylobacterium*, *Serratia*, *Streptomyces*, *Azospirillum*, *Herbaspirillum* and *Rhizobium* can be mentioned [63, 64]. The latter can establish an effective symbiotic relationship with plant species of the Leguminosae

#### **Figure 2.**

*Antimicrobial Resistance - A One Health Perspective*

*cassia*

*sciophilum*

*S. cavourensis Cinnamomum* 

*Luteibacter* sp. *Astrocaryum* 

*Streptomyces* sp. *Epipremnum* 

*aureum*

**Endophytic fungi**

The rhizosphere is a complex and dynamic region, where bacteria (including Plant Growth-Promoting Rhizobacteria—PGPR), fungi (including Arbuscular Mycorrhizal Fungi – AMF), oomycetes, viruses and archaea are attracted by chemical compounds (sugars, proteins, fatty acids, organics acids, vitamins, and other cellular components) released in the vicinity of the plant roots [16, 52, 53]. These rhizodeposits are used as carbon sources by microorganisms and represent an essential source of carbon allocated to the roots and available to plants through photosynthesis [54]. Rhizodeposits also contain secondary metabolites (flavonoids, antimicrobials and others) involved in establishing symbiosis or repelling plant pathogens and

*Secondary metabolites produced by endophytic fungi and bacteria with antimicrobial activity (2010–2020).*

**Endophyte Host plant Compound Target strain Reference**

1-Monolinolein, bafilomycin D; nonactic acid; daidzein

(*R*)-2-hydroxy-13 methyltetradecanoic acid, (*R*)-3-hydroxy-14methylpentadecanoic

13-methyltetradecanoic acid; 9Z-hexadecenoic acid, 15-methyl-9*Z*hexadecenoic acid

Phenylalanine-arginine β-naphthylamide

acid, (*S*)-βhydroxypalmitic acid; (*R*)-3-hydroxy-15 methylhexadecanoic acid, (*R*)-3-hydroxy-13-methyltetradecanoic

acid,

3′-Hydroxydaidzein *S. epidermidis*

*S. aureus* MRSA (ATCC 33591)

MRSE (ATCC 35984)

*Mycobacterium tuberculosis*

*B. cereus* (ATCC11778) *E. faecium* (ATCC51559) *A. baumannii* (ATCC19606)

*S. aureus* MRSA [48]

[47]

[49]

The establishment of the symbiotic plant-PGPR interaction in the rhizosphere can favor the plant growth through direct and indirect mechanisms. The first one includes the fixation of atmospheric nitrogen [57], phosphate solubilization [58] or any other process capable of supplying the plant with some of its previously unavailable nutrients. Many PGPRs also produce phytohormones, such as auxins (Indole-3-acetic acid) and cytokinin, which exert strong effects on root and shoot growth, respectively [59–61]. The indirect mechanisms of plant growth prevent the deleterious effects of pathogens and include competition for nutrients and niches, induction of systemic resistance (Jasmonic acid (JA), and ethylene), and lytic

**78**

pests [55, 56].

**Table 1.**

*Basic scheme of the rhizospheric space showing saprophytic and symbiotic bacteria and fungi, including arbuscular mycorrhizal fungi. Adapted from [16].*



#### **Table 2.**

*Secondary metabolites produced by rhizosphere-derived microorganisms and antimicrobial activity against pathogenic microbes.*

family and colonize the host plant's root system and form nodules, increasing biological nitrogen fixation, growth and yield of crops [65, 66]. AMF also plays a crucial role in plant health, increasing the efficiency of mineral uptake to promote growth and suppress pathogens [67, 68]. *Aspergillus*, *Fusarium*, *Penicillium*, *Verticillium*, and *Trichoderma* are among the most common fungi genera in the soil [69, 70].

**81**

by *Acinetobacter baumannii*.

*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules…*

rhizosphere microorganisms for other biotechnological purposes.

antibiotics are processed by this group of microorganisms [89–91].

high antibiotic activity against *E. coli* and *S. aureus*.

**4. Actinobacteria and natural antimicrobial products**

Due to its fundamental function in suppressing pathogens, as well as endophytes, rhizospheric fungi and bacteria, these microorganisms have attracted the attention of researchers as a new source of valuable bioactive metabolites with antimicrobial activity [71–73]. Since antibiotic resistance is a serious global health concern [74], exploring the potential of these microorganisms to discover novel medicine is also of great urgency. In this way, in recent years, secondary metabolites partially or totally identified from microorganisms that inhabit the rhizosphere have been shown to possess antimicrobial activities against important pathogen agents. **Table 2** provides an overview of selected studies that represent significant advances in the search for secondary metabolites produced from rhizospheric fungi and bacteria tested against resistant and multidrug-resistant microorganisms.

Therefore, these and other studies emphasize the vital importance of continuing scientific research to find new antimicrobials and other compounds produced from

Actinobacteria phyla have a high G + C DNA content and share both the characteristics of bacteria and fungi. These Gram-positive filamentous bacteria belong to one of the largest taxonomic groups recognized in the Bacteria domain, widely

In terms of metabolite production, the *Streptomyces* genus (**Figure 3**) stands out from other microorganisms due to its variety of bioactive substances and secondary metabolites of economic interest, since more than 80% of the industrially produced

*Streptomyces tubercidicus* is known to produce tubercidin, a potent substance that can inhibit several metabolic processes, including pathogens, such as *Trypanosoma cruzi*, viruses, fungi, and present a cytotoxic activity. However, few studies have been done on the isolation of *S. tubercidicus* and only four have been published in the production of bioactive substances [92, 93]. Ratti [94] endophytically isolated the strain of *Streptomyces tubercidicus* (RND-C) from *Solanum lycocarpum* Saint Hill, a medicinal plant typically found in the Brazilian tropical savannah, known for its anti-inflammatory properties. The fractions of the Natural product extract showed

The development of biofilm inhibitors has become a priority in recent years. Bacterial biofilms can tolerate antibiotics and host defense systems, leading to the emergence of drug-resistant and totally drug-resistant infections. As previously mentioned, *Acinetobacter baumannii* leads the list of priority pathogens resistant to antibiotics; therefore, biofilm inhibitors can be applied to decrease antibiotic tolerance by bacteria [95–97]. In this context, [96] conducted a study involving a mutasynthetic approach. Wild-type of *Streptomyces gandocaensis*, isolated from the marine sediment of the island of Punta Mona, in Costa Rica, was ribosome-engineered based on a streptomycin-resistant phenotypes of *S. gandocaensis*, resulting in the activation and improvement of the production of active metabolites. The results showed a production of new substances called cahuitamycins, a peptidic metabolite that showed a potent inhibition in the formation of the biofilm produced

Other studies report different strategies to successfully induce secondary metabolism and, subsequently, produce compounds that are not produced under usual growing conditions. Cryptic genes consist of silent sequences of DNA that are not expressed during the life cycle of a microorganism and can occur through mutations and recombination processes in a few members of a population [98–100].

*DOI: http://dx.doi.org/10.5772/intechopen.93598*

distributed across ecosystems [86–88].

*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules… DOI: http://dx.doi.org/10.5772/intechopen.93598*

Due to its fundamental function in suppressing pathogens, as well as endophytes, rhizospheric fungi and bacteria, these microorganisms have attracted the attention of researchers as a new source of valuable bioactive metabolites with antimicrobial activity [71–73]. Since antibiotic resistance is a serious global health concern [74], exploring the potential of these microorganisms to discover novel medicine is also of great urgency. In this way, in recent years, secondary metabolites partially or totally identified from microorganisms that inhabit the rhizosphere have been shown to possess antimicrobial activities against important pathogen agents. **Table 2** provides an overview of selected studies that represent significant advances in the search for secondary metabolites produced from rhizospheric fungi and bacteria tested against resistant and multidrug-resistant microorganisms.

Therefore, these and other studies emphasize the vital importance of continuing scientific research to find new antimicrobials and other compounds produced from rhizosphere microorganisms for other biotechnological purposes.

#### **4. Actinobacteria and natural antimicrobial products**

Actinobacteria phyla have a high G + C DNA content and share both the characteristics of bacteria and fungi. These Gram-positive filamentous bacteria belong to one of the largest taxonomic groups recognized in the Bacteria domain, widely distributed across ecosystems [86–88].

In terms of metabolite production, the *Streptomyces* genus (**Figure 3**) stands out from other microorganisms due to its variety of bioactive substances and secondary metabolites of economic interest, since more than 80% of the industrially produced antibiotics are processed by this group of microorganisms [89–91].

*Streptomyces tubercidicus* is known to produce tubercidin, a potent substance that can inhibit several metabolic processes, including pathogens, such as *Trypanosoma cruzi*, viruses, fungi, and present a cytotoxic activity. However, few studies have been done on the isolation of *S. tubercidicus* and only four have been published in the production of bioactive substances [92, 93]. Ratti [94] endophytically isolated the strain of *Streptomyces tubercidicus* (RND-C) from *Solanum lycocarpum* Saint Hill, a medicinal plant typically found in the Brazilian tropical savannah, known for its anti-inflammatory properties. The fractions of the Natural product extract showed high antibiotic activity against *E. coli* and *S. aureus*.

The development of biofilm inhibitors has become a priority in recent years. Bacterial biofilms can tolerate antibiotics and host defense systems, leading to the emergence of drug-resistant and totally drug-resistant infections. As previously mentioned, *Acinetobacter baumannii* leads the list of priority pathogens resistant to antibiotics; therefore, biofilm inhibitors can be applied to decrease antibiotic tolerance by bacteria [95–97]. In this context, [96] conducted a study involving a mutasynthetic approach. Wild-type of *Streptomyces gandocaensis*, isolated from the marine sediment of the island of Punta Mona, in Costa Rica, was ribosome-engineered based on a streptomycin-resistant phenotypes of *S. gandocaensis*, resulting in the activation and improvement of the production of active metabolites. The results showed a production of new substances called cahuitamycins, a peptidic metabolite that showed a potent inhibition in the formation of the biofilm produced by *Acinetobacter baumannii*.

Other studies report different strategies to successfully induce secondary metabolism and, subsequently, produce compounds that are not produced under usual growing conditions. Cryptic genes consist of silent sequences of DNA that are not expressed during the life cycle of a microorganism and can occur through mutations and recombination processes in a few members of a population [98–100].

*Antimicrobial Resistance - A One Health Perspective*

**Compound/extracts Target strains Reference**

(NCIM-2079)

*E. coli* (ATCC 25922) [80]

*Shigella flexneri (*ATCC 12022) *K. pneumonia* (ATCC

*Salmonella enterica* (ATCC 14028)

(UFPEDA-86)

(UFPEDA-02)

(UFPEDA-700) *C. albicans* (UFPEDA-1007)

*S. aureus S. pneumonia*

(MTCC 96)

*Enterococcus* VRE

(ATCC 43300)

*S. aureus* MRSA (ATCC700699)

*S. aureus* MRSA [82]

700603)

*B. cereus* (NCIM-2016) *B. subtilis* (NCIM-2699) *E. coli* (NCIM-2685) *K. pneumoniae* (NCIM-2957) *Vibrio cholerae* (MTCC-3905)

[79]

[81]

[83]

[84]

[85]

Ethyl acetate extract *S. aureus*

3,6,18-trione, 9,10-dihydro-12 -hydroxyl-2methyl-5-(phenyl methyl)(5-alpha, 10- alpha) dihydroergotamine (C3) and dipropyl—S-propyl ester (C4)

*Streptomyces* sp*.* Crude extract *B. subtilis*

included aldehydes, alkynes, 2 aromatic rings, alkanes and alkynes

*Pantoea agglomerans* 1-Octadecane and 1-nonadecanol *Klebsiella* sp.

*Streptomyces* strain M7 Actinomycins *S. aureus* MRSA

(1,1-Dichloropentane (DCP) (76%) - major compound in partial

purification)

*Micromonospora* sp. A2 - Ethyl acetate extract; − FT-IR

Ethanolic fraction *S. aureus*

Ethyl acetate fraction *S. aureus* (MRSA)

Ethyl acetate extract *S. aureus* MRSA

**Rhizospheric microorganism**

*Streptomyces* sp**.** SRDP-H03

*Exiguobacterium mexicanum* MSSRFS9

*Streptomyces* sp. VITBKA3

*pathogenic microbes.*

**80**

**Table 2.**

family and colonize the host plant's root system and form nodules, increasing biological nitrogen fixation, growth and yield of crops [65, 66]. AMF also plays a crucial role in plant health, increasing the efficiency of mineral uptake to promote growth and suppress pathogens [67, 68]. *Aspergillus*, *Fusarium*, *Penicillium*, *Verticillium*, and

*Secondary metabolites produced by rhizosphere-derived microorganisms and antimicrobial activity against* 

*Trichoderma* are among the most common fungi genera in the soil [69, 70].

#### **Figure 3.**

(A) *Antifungal activity produced by the endophytic Streptomyces sp. during the isolation.* (B–D) *Diversity of rhizospheric streptomycete colonies.*

In this context, cultured actinobacteria combined with mycolic acid-containing bacteria (*Rhodococcus erythropolis*, *Dietzia* spp., *Nocardia* spp., *Williamsia* spp., *Gordonia* spp., *Mycobacterium* spp., and *Corynebacterium* spp.) has been a useful approach for the discovery of antimicrobial natural products [99, 101–103]. However, [102] suggests that mycolic acid is insufficient to activate these cryptic genes in *Streptomyces lividans* under monoculture conditions. According to the report, the direct attachment of *S. lividans* cells on the mycolic acid-containing bacteria is crucial for the successful activation of secondary metabolism.

Caraballo-Rodríguez [3] tested the endophytic actinobacteria *Streptomyces cattleya* RLe1, *S. mobaraensis* RLe3, *S. albospinus* RLe7, *Streptomyces* sp. RLe9 and *Kytasatospora cystarginea* RLe10 co-cultured with endophytic fungi *Coniochaeta* sp. FLe4 and *Colletotrichum boninense* isolated from the Brazilian medicinal plant *Lychnophora ericoides*. The authors identified the broad-spectrum angucycline derived from *S. mobaraensis* and two molecules produced by endophytic fungi.

As already mentioned, the process of antibiotic resistance is spreading rapidly in relation to the discovery of new compounds and their introduction into clinical practice. The CDC classifies pathogens such as *B. anthracis* as biohazard category A, whose infection is fatal, and the symptoms may be similar to a common cold [104]. The preliminary study by [105] involved the isolation of the endophytic and rhizospheric microbiome associated with the medicinal plant *Polygala* sp. Natural products extracts produced by rhizoplane-derived actinomycetes showed potent inhibition against *A. baumannii*, *B. anthracis*, *E. coli* CFT073, *L. monocytogenes*, MR *S. aureus*, *S. enterica*, and *S. flexneri*.

*Caryocar brasiliense*, known as Pequi, is a tree native to the Brazilian savannah and commonly used in folk medicine. Bioactive substances such as gallic acid, quinic acid, ellagic acid, glucogalin, and corilagin were found in its extracts. In addition, they show a growth inhibition rate of the phytopathogenic *Alternaria solani* [106]. A rhizospheric strain of *Streptomyces* sp. was isolated from *C. brasiliense*, whose crude extract obtained from the axenic cultivation was able to inhibit *C. albicans*; in contrast, the co-cultured *Streptomyces* sp. extract increased the growth of *C. albicans* in 50% and promoted the inhibition of *S. aureus* [107].

**83**

*Plant-Associated Microorganisms as a Potent Bio-Factory of Active Molecules…*

Biotechnologically, the *Streptomyces* genus is known to be a skilled producer of a wide range of bioactive substances and represents an unexplored reservoir of

The scientific interest in fungal natural products gained notoriety after the paclitaxel discovery [108]. Endophytic fungi exhibit the ability to synthesize plant-derived compounds by mimicking the metabolic pathways of the host plant, which confers multifaceted applications in the fields of agriculture, medicine, and

The medicinal plant barbatimão (*Stryphnodendron adstringens*) has healing properties, antimicrobial, antioxidant, and anti-inflammatory activities, and its bark has a rich tannin-content [107, 110]. The study by [111] investigated the antimicrobial and anticancer activities of several fungi isolated from *S. adstringens*. The extract of *Nigrospora oryzae* promoted antifungal activity and inhibited the growth of *C. albicans* and *C. sphaerospermum*, while the extracts of *Diaporthe phaseolorum* and

Although toxic to humans and animals, mycotoxins are secondary metabolites known for their cytotoxic effect against malignant cells [112]. Several species of *Fusarium* and *Beauveria bassiana* are skilled producers of mycotoxins, such as Beauvericin, which promote apoptosis in mammalian cells and exhibit insecticidal properties [113, 114], while Ochratoxin A is produced by some species of fungi,

The superbug methicillin-resistant *Staphylococcus aureus* is responsible for higher

mortality rates in the community and hospital-acquired infections [117] due to its ability to resist multiple classes of antibiotics [118, 119]. In this context, fungal alkaloids are known for their potent antibacterial, anticancer, antiparasitic, and insecticidal activities [120]. In [121], a novel alkaloid compound, GKK1032C, is reported, which is produced by *Penicillium* sp. endophytically associated with the mangrove plant, exhibiting potent activity against methicillin-resistant *S. aureus*. Saponins exhibit a wide range of biological activities, such as antifungal, hemolytic, antiviral, and immunomodulatory. These compounds represent an alternative to overcome multidrug-resistant microorganisms since they can act synergistically with antibiotics. Moreover, medicines that were once considered ineffective due to resistance problems might be effective for resistant microbes [122, 123]. Nevertheless, as reported by [124], saponin from *Quillaja saponaria* bark did not present synergistic activity in combination with ampicillin, streptomycin, and ciprofloxacin against a clinical strain of *E. coli*. In a short communication from [125], the isolation of triterpenoid saponins produced by the endophytic fungi *Fusarium oxysporum* and *Aspergillus niger* isolated from *Panax notoginseng* was reported. According to the authors, saponin extracts exhibited moderate to high

Antibiotic-resistant microbes represent a severe threat to the public health system worldwide. Furthermore, multidrug-resistant 'ESKAPE' organisms (*Enterococcus* spp., *Staphylococcus aureus*, *Klebsiella* spp., *Acinetobacter baumannii*, *Pseudomonas aeruginosa* and *Enterobacter* spp) are strictly associated with high rates

*DOI: http://dx.doi.org/10.5772/intechopen.93598*

**5. Natural products and endophytic fungi**

*Xylaria* spp. presented anticancer activities.

such as *Aspergillus* spp. and *Penicillium* spp. [115, 116].

antimicrobial activity against the pathogens tested.

of morbidity and mortality, as well as an economic impact.

**6. Concluding remarks**

unique chemical structures.

pharmaceuticals [109].

Biotechnologically, the *Streptomyces* genus is known to be a skilled producer of a wide range of bioactive substances and represents an unexplored reservoir of unique chemical structures.
