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Antibiotic-resistant pathogens are a public health threat that has rapidly spread over decades due to continuous and uncontrolled administration of antimicrobial medicines, becoming an ever-increasing worldwide concern. Since the past decade, no significant innovations have been made, so the search for new compounds that face multidrug-resistant pathogens is critically important. Plant-symbiont microorganisms are capable of producing a variety of bioactive natural products, making it possible to treat several infectious diseases. Biotechnological processes using microorganisms have been increasing in recent years since the discovery of Paclitaxel, an important antimitotic produced by the endophyte Taxomyces andreanae. It was isolated for the first time from the native tree of Pacific Taxus brevifolia. Several studies have demonstrated the isolation and characterization of promising and potent substances capable of inhibiting these pathogens. In addition, both rhizospheric and endophytic communities represent an unexplored reserve of unique chemical structures for drug development. This chapter focuses on the potential of plant-derived microorganisms as a source of bioactive substances and the perspectives for further studies and their application.
Laboratory of Microbiology and Biomolecules—LaMiB, Department of Morphology and Pathology, Federal University of São Carlos, Brazil
Biotechnology Graduate Program, Federal University of Sao Carlos, Brazil
Andréa Cristina Bogas
Laboratory of Microbiology and Biomolecules—LaMiB, Department of Morphology and Pathology, Federal University of São Carlos, Brazil
Biotechnology Graduate Program, Federal University of Sao Carlos, Brazil
Cristina Paiva de Sousa*
Laboratory of Microbiology and Biomolecules—LaMiB, Department of Morphology and Pathology, Federal University of São Carlos, Brazil
Biotechnology Graduate Program, Federal University of Sao Carlos, Brazil
*Address all correspondence to: prokarya@ufscar.br
1. Introduction
The discovery of medicines in the treatment of infectious diseases represents one of the most significant accomplishments of humankind. The introduction of antibiotics made it possible to treat previously incurable diseases.
Major classes of antibiotics were discovered between the 1940s and 1960s, where soil-derived actinobacteria produced most of them. However, several decades passed without significant innovations until the discovery and development of oxazolidinones in 2010 (Figure 1). Moreover, the continuous uncontrolled use of these medicines favored the rapid spread of resistant pathogens, where new compounds were discovered, and their introduction into clinical practice was not fast enough [1, 2, 3, 4, 5].
Figure 1.
Timeline of antibiotic discovery that shows no new classes of antibiotics between the years 1962 and 2000 adapted from: [6, 7].
The CDC (Centers for Disease Control and Prevention) has recognized the emerging antibiotic resistance as a significant threat to public health [8]. Superbugs, such as Methicillin-resistant Staphylococcus aureus (MRSA), show antibiotic resistance rates that surpass 50% in 5 out of 6 world regions; in contrast, the multidrug-resistant Acinetobacter baumannii, described as a dangerous agent by the Society of Infectious Diseases of America (SIDA), is a notable threat in intensive care units (ICUs) due to the development of resistance to broad-spectrum antibiotics [5, 8, 9, 10].
Therefore, the search for compounds and the exploration of niches that harbor microorganisms that produce bioactive metabolites are critically important [11, 12, 13]. Several studies have shown that plant tissues represent a rich source of natural products for pharmaceutical and biotechnological interest. Most of these compounds are produced by microorganisms that live in intimate interaction with the host plant without causing damage; therefore, they are known as endophytes [11, 14, 15].
In the same context, the rhizosphere’s microbiome can exert profound direct and indirect effects on plant growth, nutrition, and health in natural ecosystems. Its micro-community (bacteria, oomycetes, viruses, archeas, fungi and arbuscular mycorrhizae) is attracted and fed by nutrients, exudates, border cells and mucilage that are released by the root of the plant [16].
Relevant studies have reported potent antimicrobial compounds, such as teixobactin, isolated from the non-cultivable bacterium Eleftheria terrae [17]. According to the authors in [17], teixobactin inhibits cell wall synthesis by binding to the highly conserved region of lipid precursors of peptidoglycan and teichoic acid. In addition, S. aureus and Mycobacterium tuberculosis did not develop resistance to teixobactin.
In the study by [18], endophytic fungi were isolated from the medicinal plant Orthosiphon stamineus, where 92% of them exhibited significant inhibitory activity against different species of bacterial pathogens and filamentous fungi.
Paenibacillus polymyxa can be found in several habitats. Its characteristic metabolism and production of substances enhance biotechnological applications based on the production of bioactive molecules. It is also widely applied in commercial agriculture as a bio-fertilizer grow plant promoter, biological control, and environmental remediation. In [19], P. polymyxa was endophytically isolated from Prunus spp., and the author reported the isolation of molecules which potently inhibited S. aureus and E. coli.
Herein, we address a review topic concerning the potential of rhizospheric and endophytic microorganisms as producers of antimicrobial compounds.
In 1866, de Bary outlined the first distinction between endophytes and plant pathogens. These microorganisms (typically fungi or bacteria) colonize the plant’s internal tissues and live part of its life or its entire life cycle without causing apparent damage, establishing a mutualistic interaction with the host plant. Moreover, endophytes are capable of producing beneficial substances, such as alkaloids, enzymes, antibiotics and other compounds that protect and help the plant under stress conditions in exchange for nutrients and protection provided by the host plant [14, 15, 20, 21, 22].
In this context, plants have served humanity for centuries and led to the discovery of novel bioactive compounds. However, concerns regarding biodiversity and conservation, as well as large quantities of plant tissue, are required to produce sufficient yields of compounds [23]. According to [24], paclitaxel isolation requires about 10,000 kg of T. brevifolia bark to yield 1 kg. On the other hand, several studies have shown that endophytes may produce similar or even the same bioactive compounds as their plant hosts [20, 23, 25].
Fungi are skilled producers of natural products, including antitumor agents, cholesterol-lowering agents, immunosuppressants and antibiotics [25, 26]. The study by [27] detected potent antimicrobial properties of the natural product extract (NPE) of endophytic fungi associated with Myrciaria floribunda, Alchornea castaneifolia and Eugenia aff. Bimarginata against several pathogens. The methanolic extracts presented MIC values ranging from 7.8 to 1000 μg/mL against C. krusei, C. parapsilosis, C. neoformans, C. albicans, and C. glabrata. The inhibition of S. aureus and B. cereus ranged from 7.8 to >1000 μg/mL. Also, endophytic fungi were isolated from Cinnamomum mercadoi, a medicinal tree endemic to the Philippines. The ethyl acetate extract of Fusarium sp. presented moderate inhibition against E. coli, E. aerogenes, S. aureus, and B. cereus with minimum inhibitory concentrations of 2.1, 4.2, 4.2, and 3.8 mg/mL, respectively [28].
Therefore, the emerging use of endophytes in the research and development of new drugs represents the most successful example of bioactive natural products in medicine, pharmaceutical and biotechnological applications. Table 1 provides an idea of some secondary metabolites of endophytic fungi and bacteria tested against resistant and multidrug-resistant microorganisms.
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].
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, 60, 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 enzymes (chitinase, pectinase, cellulase, glucanase, protease, xylanase), siderophore, bacteriocins and antibiotics production [62] (Figure 2).
Figure 2.
Basic scheme of the rhizospheric space showing saprophytic and symbiotic bacteria and fungi, including arbuscular mycorrhizal fungi. Adapted from [16].
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 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].
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, 72, 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.
(1,1-Dichloropentane (DCP) (76%) - major compound in partial purification)
S. aureus MRSA (ATCC700699)
Table 2.
Secondary metabolites produced by rhizosphere-derived microorganisms and antimicrobial activity against pathogenic microbes.
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, 87, 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, 90, 91].
Figure 3.
(A) Antifungal activity produced by the endophytic Streptomyces sp. during the isolation. (B–D) Diversity of rhizospheric streptomycete colonies.
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, 96, 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, 99, 100]. 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, 102, 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].
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.
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 pharmaceuticals [109].
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 Xylaria spp. presented anticancer activities.
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, such as Aspergillus spp. and Penicillium spp. [115, 116].
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 antimicrobial activity against the pathogens tested.
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 of morbidity and mortality, as well as an economic impact.
In this chapter, we highlighted the strategies of antimicrobial drug discovery produced by endophytes and rhizospheric microorganisms, since enormous untapped resources remain. The use of such microbes in biotechnological processes has increased in recent years, as they are skilled producers of natural bioactive products that can be used as pharmaceuticals to face this ever-increasing threat.
This manuscript was financially supported by Sao Paulo State Research Support Foundation (FAPESP) through project number 2016/13423-5.
References
1.Lewis K, Epstein S, D’Onofrio A, Ling LL. Uncultured microorganisms as a source of secondary metabolites. Journal of Antibiotics (Tokyo). 2010;63(8):468-476. DOI: 10.1038/ja.2010.87
2.Piza ACMT, Hokka C, Sousa C. Endophytic actinomycetes from Miconia albicans (Sw.) Triana (Melastomataceae) and evaluation of its antimicrobial activity. Journal of Science Research and Reports. 2015;4(4):281-291. DOI: 10.9734/JSRR/2015/13237
3.Caraballo-Rodríguez AM, Dorrestein PC, Pupo MT. Molecular inter-kingdom interactions of endophytes isolated from Lychnophora ericoides. Scientific Reports. 2017;7(1):5373. Published: July 14, 2017. DOI: 10.1038/s41598-017-05532-5
4.Nicolaou KC, Rigol S. A brief history of antibiotics and select advances in their synthesis. Journal of Antibiotics (Tokyo). 2018;71(2):153-184. DOI: 10.1038/ja.2017.62
5.Chen CH, Kuo HY, Hsu PJ, et al. Clonal spread of carbapenem-resistant Acinetobacter baumannii across a community hospital and its affiliated long-term care facilities: A cross sectional study. Journal of Microbiology, Immunology, and Infection. 2018;51(3):377-384. DOI: 10.1016/j.jmii.2017.08.001
7.Walsh CT, Wencewicz TA. Prospects for new antibiotics: A molecule-centered perspective. Journal of Antibiotics (Tokyo). 2014;67(1):7-22. DOI: 10.1038/ja.2013.49
8.Nair DR, Chen J, Monteiro JM, et al. A quinolinol-based small molecule with anti-MRSA activity that targets bacterial membrane and promotes fermentative metabolism. Journal of Antibiotics (Tokyo). 2017;70(10):1009-1019. DOI: 10.1038/ja.2017.79
9.Huggins WM, Minrovic BM, Corey BW, et al. 1,2,4-Triazolidine-3-thiones as narrow spectrum antibiotics against multidrug-resistant Acinetobacter baumannii. ACS Medicinal Chemistry Letters. 2016;8(1):27-31. Published: November 12, 2016. DOI: 10.1021/acsmedchemlett.6b00296
10.Sommer MOA, Munck C, Toft-Kehler RV, Andersson DI. Prediction of antibiotic resistance: Time for a new preclinical paradigm? Nature Reviews. Microbiology. 2017;15(11):689-696. DOI: 10.1038/nrmicro.2017.75
11.Joseph B, Pryia MR. Bioactive compounds from endophytes and their potential in pharmaceutical effect: A review. American Journal of Biochemistry and Molecular Biology. 2011;1(3):291-309. DOI: 10.3923/ajbmb.2011.291.309
12.Matsumoto A, Takahashi Y. Endophytic actinomycetes: Promising source of novel bioactive compounds. Journal of Antibiotics (Tokyo). 2017;70(5):514-519. DOI: 10.1038/ja.2017.20
13.Vigliotta G, Giordano D, Verdino A, et al. New compounds for a good old class: Synthesis of two Β-lactam bearing cephalosporins and their evaluation with a multidisciplinary approach. Bioorganic & Medicinal Chemistry. 2020;28(4):115302. DOI: 10.1016/j.bmc.2019.115302
14.Azevedo JL, Maccheroni W Jr, Pereira JO, De Araújo WL. Endophytic microorganisms: A review on insect control and recent advances on tropical plants. Electronic Journal of Biotechnology. 2000;3:15-16. DOI: 10.2225/vol3-issue1fulltext-4
15.Pacifico D, Squartini A, Crucitti D, et al. The role of the Endophytic microbiome in the grapevine response to environmental triggers. Frontiers in Plant Science. 2019;10:1256. Published: October 9, 2019. DOI: 10.3389/fpls.2019.01256
16.Philippot L, Raaijmakers JM, Lemanceau P, van der Putten WH. Going back to the roots: The microbial ecology of the rhizosphere. Nature Reviews. Microbiology. 2013;11(11):789-799. DOI: 10.1038/nrmicro3109
17.Ling LL, Schneider T, Peoples AJ, et al. A new antibiotic kills pathogens without detectable resistance [published correction appears in Nature. 2015 Apr 16;520(7547):388]. Nature. 2015;517(7535):455-459. DOI: 10.1038/nature14098
18.Tong WY, Darah I, Latiffah Z. Antimicrobial activities of endophytic fungal isolates from medicinal herb Orthosiphon stamineus Benth. Journal of Medicinal Plant Research: Planta Medica. 2011;5:831-836
19.Serrano NFG. Purificação e caracterização bioquímica de substâncias bioativas produzidas por endofítico isolado de Prunus spp. Dissertation. Sao Carlos, Sao Paulo, Brazil: Federal University of São Carlos. 2009
20.Gouda S, Das G, Sen SK, Shin HS, Patra JK. Endophytes: A treasure house of bioactive compounds of medicinal importance. Frontiers in Microbiology. 2016;7:1538. Published: September 2016, 29. DOI: 10.3389/fmicb.2016.01538
21.Kandel SL, Joubert PM, Doty SL. Bacterial endophyte colonization and distribution within plants. Microorganisms. 2017;5(4):77. Published: November 25, 2017. DOI: 10.3390/microorganisms5040077
22.White JF, Kingsley KL, Zhang Q, et al. Review: Endophytic microbes and their potential applications in crop management. Pest Management Science. 2019;75(10):2558-2565. DOI: 10.1002/ps.5527
23.Alvin A, Miller KI, Neilan BA. Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds. Microbiological Research. 2014;169(7-8):483-495. DOI: 10.1016/j.micres.2013.12.009
24.Stierle A, Strobel G, Stierle D. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science. 1993;260(5105):214-216. DOI: 10.1126/science.8097061
25.Strobel G, Daisy B, Castillo U, Harper J. Natural products from endophytic microorganisms. Journal of Natural Products. 2004;67(2):257-268. DOI: 10.1021/np030397v
26.Pan F, Su TJ, Cai SM, Wu W. Fungal endophyte-derived Fritillaria unibracteata var. wabuensis: diversity, antioxidant capacities in vitro and relations to phenolic, flavonoid or saponin compounds. Scientific Reports. 2017;7:42008. Published: February 6, 2017. DOI: 10.1038/srep42008
27.Vaz ABM, Brandão LR, Vieira MLA, Pimenta RS, Morais PB, Sobral MEG, et al. Diversity and antimicrobial activity of fungal endophyte communities associated with plants of Brazilian savanna ecosystems. African Journal of Microbiology Research. 2012;6(13):3173-3185. DOI: 10.5897/AJMR11.1359
28.Marcellano JP, Collanto AS, Fuentes RG. Antibacterial activity of endophytic fungi isolated from the bark of Cinnamomum mercadoi. The Pharmacogenomics Journal. 2017;9(3):405-409. DOI: 10.5530/pj.2017.3.69
29.Dang L, Li G, Yang Z, et al. Chemical constituents from the endophytic fungus Trichoderma ovalisporum isolated from Panax notoginseng. Annales de Microbiologie. 2010;60:317-320 https://doi.org/10.1007/s13213-010-0043-2
30.Wang QX, Li SF, Zhao F, et al. Chemical constituents from endophytic fungus Fusarium oxysporum. Fitoterapia. 2011;82(5):777-781. DOI: 10.1016/j.fitote.2011.04.002
31.Sebastianes FL, Cabedo N, El Aouad N, et al. 3-hydroxypropionic acid as an antibacterial agent from endophytic fungi Diaporthe phaseolorum. Current Microbiology. 2012;65(5):622-632. DOI: 10.1007/s00284-012-0206-4
32.Subban K, Subramani R, Johnpaul M. A novel antibacterial and antifungal phenolic compound from the endophytic fungus Pestalotiopsis mangiferae. Natural Product Research. 2013;27(16):1445-1449. DOI: 10.1080/14786419.2012.722091
33.Ratnaweera PB, Williams DE, de Silva ED, Wijesundera RL, Dalisay DS, Andersen RJ. Helvolic acid, an antibacterial nortriterpenoid from a fungal endophyte, Xylaria sp. of orchid Anoectochilus setaceus endemic to Sri Lanka. Mycology. 2014;5(1):23-28. DOI: 10.1080/21501203.2014.892905
34.Ibrahim SRM, Elkhayat ES, Mohamed GA, Khedr AIM, Fouad MA, Kotb MHR, et al. Aspernolides F and G, new butyrolactones from the endophytic fungus Aspergillus terreus. Phytochemistry Letters. 2015;14:84-90 http://doi.org/10.1016/j.phytol.2015.09.006
35.Ratnaweera PB, de Silva ED, Wijesundera RLC, Andersen RJ. Antimicrobial constituents of Hypocrea virens, an endophyte of the mangrove-associate plant Premna serratifolia L. Journal of the National Science Foundation of Sri Lanka. 2016;44:43-51. DOI: 10.4038/jnsfsr.v44i1.7980
36.He Y, Hu Z, Sun W, et al. Spiroaspertrione a, a bridged spirocyclic meroterpenoid, as a potent potentiator of oxacillin against methicillin-resistant Staphylococcus aureus from Aspergillus sp. TJ23. The Journal of Organic Chemistry. 2017;82(6):3125-3131. DOI: 10.1021/acs.joc.7b00056
37.Qiao Y, Zhang X, He Y, et al. Aspermerodione, a novel fungal metabolite with an unusual 2,6-dioxabicyclo[2.2.1]heptane skeleton, as an inhibitor of penicillin-binding protein 2a. Scientific Reports. 2018;8(1):5454. Published: April 3, 2018. DOI: 10.1038/s41598-018-23817-1
38.Hu S, Liang M, Mi Q , et al. Two new diphenyl ether derivatives from the fermentation products of the endophytic fungus Phomopsis asparagi. Chemistry of Natural Compounds. 2019;55:843-846. DOI: 10.1007/s10600-019-02828-y
39.Astuti P, Rollando R, Wahyuono S, Nurrochmad A. Antimicrobial activities of isoprene compounds produced by an endophytic fungus isolated from the leaves of Coleus amboinicus Lour. Journal of Pharmacy and Pharmacognosy Research. 2020;8(4):280-289
40.Ding L, Maier A, Fiebig HH, Lin WH, Hertweck C. A family of multicyclic indolosesquiterpenes from a bacterial endophyte. Organic & Biomolecular Chemistry. 2011;9(11):4029-4031. DOI: 10.1039/c1ob05283g
41.Ding L, Maier A, Fiebig HH, Lin WH, Peschel G, Hertweck C, et al. Eudesmenes from an endophytic Streptomyces sp. of the mangrove tree Kandelia candel. Journal of Natural Products. 2012;75(12):2223-2227. DOI: 10.1021/np300387n
42.Djinni I, Defant A, Kecha M, Mancini I. Antibacterial polyketides from the marine alga-derived endophitic Streptomyces sundarbansensis: A study on hydroxypyrone tautomerism. Marine Drugs. 2013;11(1):124-135. Published: January 10, 2013. DOI: 10.3390/md11010124
43.Yang X, Peng T, Yang Y, et al. Antimicrobial and antioxidant activities of a new benzamide from endophytic Streptomyces sp. YIM 67086. Natural Product Research. 2015;29(4):331-335. DOI: 10.1080/14786419.2014.945174
44.Khieu TN, Liu MJ, Nimaichand S, et al. Characterization and evaluation of antimicrobial and cytotoxic effects of Streptomyces sp. HUST012 isolated from medicinal plant Dracaena cochinchinensis Lour. Frontiers in Microbiology. 2015;6:574. Published 2015 Jun 8. DOI: 10.3389/fmicb.2015.00574
45.Alshaibani MM, Jalil J, Sidik NM, Edrada-Ebel R, Zin NM. Isolation and characterization of cyclo-(tryptophanyl-prolyl) and chloramphenicol from Streptomyces sp. SUK 25 with antimethicillin-resistant Staphylococcus aureus activity. Drug Design, Development and Therapy. 2016;10:1817-1827. Published: May 31, 2016. DOI: 10.2147/DDDT.S101212
46.Gos FMWR, Savi DC, Shaaban KA, et al. Antibacterial activity of endophytic actinomycetes isolated from the medicinal plant Vochysia divergens (Pantanal, Brazil). Frontiers in Microbiology. 2017;8:1642. Published: September 6, 2017. DOI: 10.3389/fmicb.2017.01642
47.Vu HT, Nguyen DT, Nguyen HQ , et al. Antimicrobial and cytotoxic properties of bioactive metabolites produced by Streptomyces cavourensis YBQ59 isolated from Cinnamomum cassia Prels in Yen Bai Province of Vietnam. Current Microbiology. 2018;75(10):1247-1255. DOI: 10.1007/s00284-018-1517-x
48.Bunbamrung N, Intaraudom C, Dramae A, et al. Antibacterial, antitubercular, antimalarial and cytotoxic substances from the endophytic Streptomyces sp. TBRC7642. Phytochemistry. 2020;172:112275. DOI: 10.1016/j.phytochem.2020.112275
49.Hartmann A, Rothballer M, Schmid M. Lorenz Hiltner, a pioneer in rhizosphere microbial ecology and soil bacteriology research. Plant and Soil. 2008;312:7-14. DOI: 10.1007/s11104-007-9514-z
50.Parray JA, Mir MY, Shameen N. Rhizosphere engineering and agricultural productivity. In: Sustainable Agriculture: Biotechniques in Plant Biology. 2019. DOI: 10.1007/978-981-13-8840-8
52.Brahmaprakash GP, Sahu PK, Lavanya G, Nair SS, Gangaraddi VK, Gupta A. Microbial Functions of the Rhizosphere. In: Singh D, Singh H, Prabha R, editors. Plant-Microbe Interactions in Agro-Ecological Perspectives; Singapore: Springer; 2019. DOI: 10.1007/978-981-10-5813-4_10
53.Dini-Andreote F, Gumiere T, Durrer A. Exploring interactions of plant microbiomes. Science in Agriculture. 2014;71:528-539. DOI: 10.1590/0103-9016-2014-0195
54.Jones D, Nguyen C, Finlay DR. Carbon flow in the rhizosphere: Carbon trading at the soil–root interface. Plant and Soil. 2009;321:5-33. DOI: 10.1007/s11104-009-9925-0
55.Hassan MK, McInroy JA, Kloepper JW. The interactions of rhizodeposits with plant growth-promoting rhizobacteria in the rhizosphere: A review. Agriculture. 2019;9(7):142. DOI: 10.3390/agriculture9070142
56.Venturi V, Keel C. Signaling in the rhizosphere. Trends in Plant Science. 2016;21(3):187-198. DOI: 10.1016/j.tplants.2016.01.005
57.Kuan KB, Othman R, Abdul Rahim K, Shamsuddin ZH. Plant growth-promoting rhizobacteria inoculation to enhance vegetative growth, nitrogen fixation and nitrogen remobilisation of maize under greenhouse conditions. PLoS One. 2016;11(3):e0152478. DOI: 10.1371/journal.pone.0152478
58.Mehta P, Walia A, Kulshrestha S, Chauhan A, Shirkot CK. Efficiency of plant growth-promoting P-solubilizing Bacillus circulans CB7 for enhancement of tomato growth under net house conditions. Journal of Basic Microbiology. 2015;55(1):33-44. DOI: 10.1002/jobm.201300562
59.Gupta G, Parihar SS, Ahirwar NK, Snehi SK, Singh V. Plant growth promoting rhizobacteria (PGPR): Current and future prospects for development of sustainable agriculture. Journal of Microbial and Biochemical Technology. 2015;7:096-102. DOI: 10.4172/1948-5948.1000188
60.Patel T, Saraf M. Biosynthesis of phytohormones from novel rhizobacterial isolates and their in vitro plant growth-promoting efficacy. Journal of Plant Interactions. 2017;12:480-487. DOI: 10.1080/17429145.2017.1392625
61.Berendsen RL, Pieterse CM, Bakker PA. The rhizosphere microbiome and plant health. Trends in Plant Science. 2012;17(8):478-486. DOI: 10.1016/j.tplants.2012.04.001
62.Yadav S, Singh K, Chandra R. Plant Growth–Promoting Rhizobacteria (PGPR) and Bioremediation of Industrial Waste. In: Chandra R, Sobti RC, editor. Microbes for Sustainable Development and Bioremediation. Boca Raton: CRC Press; 2019. DOI: 10.1201/9780429275876
63.Kour D, Rana KL, Yadav N, Yadav AN, Kumar A, Meena VS, et al. Rhizosphere microbiomes: Biodiversity, mechanisms of plant growth promotion, and biotechnological applications for sustainable agriculture. In: Kumar A, Meena V, editors. Plant Growth Promoting Rhizobacteria for Agricultural Sustainability. Singapura: Springer; 2019. DOI: 10.1007/978-981-13-7553-8_2
64.Shastri B, Kumar R. Microbial secondary metabolites and plant microbe communications in the rhizosphere. In: Singh, J.S. New and Future Developments in Microbial Biotechnology and Bioengineering. Microbes in Soil, Crop and Environmental Sustainability. B.V: Elsevier; 2019. pp. 93-111. DOI: 10.1016/B978-0-12-818258-1.00006-6
65.Alam F, Bhuiyan MA, Alam SS, Waghmode TR, Kim PJ, Lee YB. Effect of rhizobium sp. BARIRGm901 inoculation on nodulation, nitrogen fixation and yield of soybean (Glycine max) genotypes in gray terrace soil. Bioscience, Biotechnology, and Biochemistry. 2015;79(10):1660-1668. DOI: 10.1080/09168451.2015.1044931
66.Getahun A, Muleta D, Assefa F, Kiros S. Field application of Rhizobial inoculants in enhancing faba bean production in acidic soils: An innovative strategy to improve crop productivity. In: Akhtar M, editor. Salt Stress, Microbes, and Plant Interactions: Causes and Solution. Singapore: Springer; 2019. DOI: 10.1007/978-981-13-8801-9
67.Amballa H, Bhumi NR. Significance of arbuscular mycorrhizal fungi and rhizosphere microflora in plant growth and nutrition. In: Choudhary et al., editors. Plant-Microbe Interaction: An Approach to Sustainable Agriculture. Singapura: Springer; 2016. pp. 417-452. DOI: 10.1007/978-981-10-2854-0
68.Singh I, Giri B. Arbuscular mycorrhiza mediated control of plant pathogens. In: Varma A, Prasad R, Tuteja N, editors. Mycorrhiza—Nutrient Uptake, Biocontrol, Ecorestoration. Cham: Springer; 2017. DOI: 10.1007/978-3-319-68867-1
69.Brahmaprakash GP, Sahu PK, Nair GLSS, Gangaraddi VK, Gupta A. Microbial functions of the rhizosphere. In: Singh DP, Singh HB, Prabha R, editors. Plant-Microbe Interactions in Agro-Ecological Perspectives. Springer; 2017. DOI: 10.1007/978-981-10-5813-4
70.Pattnaik SS, Busi S. Rhizosphere fungi: Diversity and potential biotechnological applications. In: Yadav A, Misha S, Singh S, Gupta A, editors. Recent Advancement in White Biotechnology Through Fungi. Fungal Biology. Cham: Springer; 2019. DOI: 10.1007/978-3-030-10480-1
71.Iniyan AM, Kannan RR, Vincent SGP. Characterization of culturable actinomycetes associated with halophytic rhizosphere as potential source of antibiotics. Proceedings of the National Academy of Sciences, India Section B: Biological Sciences. 2015;87:233-242. DOI: 10.1007/s40011-015-0601-2
72.Muleta A, Assefa F. Isolation and screening of antibiotic producing actinomycetes from rhizosphere and agricultural soils. African Journal of Biotechnology. 2018;17:700-714. DOI: 10.5897/AJB2017.16080
73.Zhang TY, Wu YY, Zhang MY, Cheng J, Dube B, et al. New antimicrobial compounds produced by Seltsamia galinsogisoli sp. nov., isolated from Galinsoga parvifora as potential inhibitors of FtsZ. Scientific Reports. 2019;9:8319. DOI: 10.1038/s41598-019-44810-2
74.Ahmad M, Khan AU. Global economic impact of antibiotic resistance: A review. Journal of Global Antimicrobial Resistance. 2019;19:313-316. DOI: 10.1016/j.jgar.2019.05.024
75.Chang M, Wang J, Tian F, Zhang Q , Ye B. Antibacterial activity of secondary metabolites from Aspergillus awamori F12 isolated from rhizospheric soil of Rhizophora stylosa Griff. Chinese: Wei Sheng Wu Xue Bao; Oct 2010;50(10):1385-1391. PMID: 21141475
76.Xu R, Li XM, Wang BG. Penicisimpins A–C, three new dihydroisocoumarins from Penicillium simplicissimum MA-332, a marine fungus derived from the rhizosphere of the mangrove plant Bruguiera sexangula var. rhynchopetala. Phytochemistry Letters. 2016;17:114-118. DOI: 10.1016/j.phytol.2016.07.003
77.Singh A, Kumar M, Salar RK. Isolation of a novel antimicrobial compounds producing fungus Aspergillus Niger MTCC 12676 and evaluation of its antimicrobial activity against selected pathogenic microorganisms. Journal of Pure and Applied Microbiology. 2017;11(3):1457-1464. DOI: 10.22207/JPAM.11.3.29
78.Zaghian S, Shokri D, Emtiazi G. Co-production of a UV-stable bacteriocin-like inhibitory substance (BLIS) and indole-3-acetic acid hormone (IAA) and their optimization by Taguchi design in Bacillus pumilus. Annales de Microbiologie. 2011;62:1189-1197. DOI: 10.1007/s13213-011-0359-6
79.Rakesh KN, Junaid S, Dileep N, Kekuda PTR. Antibacterial and antioxidant activities of Streptomyces species SRDP-H03 isolated from soil of Hosudi, Karnataka, India. Journal of Drug Delivery Science and Technology. 2013;(4):47-53. DOI: 10.22270/jddt.v3i4.568
80.Shanthakumar SP, Duraisamy P, Vishwanath G, Selvanesan BC, Ramaraj V, Vasantharaj David B. Broad spectrum antimicrobial compounds from the bacterium Exiguobacterium mexicanum MSSRFS9. Microbiological Research. 2015;178:59-65. DOI: 10.1016/j.micres.2015.06.007
81.Silva-Lacerda GR, Santana RC, Vicalvi-Costa MC, et al. Antimicrobial potential of actinobacteria isolated from the rhizosphere of the Caatinga biome plant Caesalpinia pyramidalis Tul. Genetics and Molecular Research. 2016;15(1):15017488. Published: March 4, 2016. DOI: 10.4238/gmr.15017488
82.Abdullahi U, Obidah JS, Jada SM. Characterization of antibiotics inhibitory to methicillin resistant Staphylococcus aureus (MRSA) from soil actinomycetes. Asian Journal of Research in Medical and Pharmaceutical Sciences. 2018;4(2):1-13. DOI: 10.9734/AJRIMPS/2018/39742
83.Nair NM, Kanthasamy R, Mahesh R, Selvam SIK, Ramalakshmi S. Production and characterization of antimicrobials from isolate Pantoea agglomerans of Medicago sativa plant rhizosphere soil. Journal of Applied and Natural Sciences. 2019;11(2):267-272. DOI: 10.31018/ jans.v11i2.203
84.Sharma M, Manhas RK. Purification and characterization of actinomycins from Streptomyces strain M7 active against methicillin resistant Staphylococcus aureus and vancomycin resistant Enterococcus. BMC Microbiology. 2019;19(1):44. Published: February 19, 2019. DOI: 10.1186/s12866-019-1405-y
85.Bhakyashree K, Kannabiran K. Actinomycetes mediated targeting of drug resistant MRSA pathogens. Journal of King Saud University—Science. 2020;32:260-264. DOI: 10.1016/j.jksus.2018.04.034
86.Barka EA, Vatsa P, Sanchez L, et al. Taxonomy, physiology, and natural products of actinobacteria [published correction appears in Microbiol Mol Biol Rev. 2016 Nov 9;80(4): iii]. Microbiology and Molecular Biology Reviews. 2015;80(1):1-43. Published: November 25, 2015. DOI: 10.1128/MMBR.00019-15
87.Anandan R, Dharumadurai D, Manogaran GP. An Introduction to Actinobacteria. In: Dhanasekaran D, Jiang Y, editors. Actinobacteria - Basics and Biotechnological Applications. IntechOpen; 2016. DOI: 10.5772/62329
88.Azman AS, Mawang CI, Khairat JE, AbuBakar S. Actinobacteria-a promising natural source of anti-biofilm agents. International Microbiology. 2019;22(4):403-409. DOI: 10.1007/s10123-019-00066-4
89.Bérdy J. Bioactive Microbial Metabolites [published correction appears in J Antibiot (Tokyo). 2005 Apr;58(4):C-1]. Journal of Antibiotics (Tokyo). 2005;58(1):1-26. DOI: 10.1038/ja.2005.1
90.Qin S, Xing K, Jiang JH, Xu LH, Li WJ. Biodiversity, bioactive natural products and biotechnological potential of plant-associated endophytic actinobacteria. Applied Microbiology and Biotechnology. 2011;89(3):457-473. DOI: 10.1007/s00253-010-2923-6
91.Genilloud O. Actinomycetes: Still a source of novel antibiotics. Natural Product Reports. 2017;34(10):1203-1232. DOI: 10.1039/c7np00026j
92.Smulson ME, Suhadolnik RJ. The biosynthesis of the 7-deazaadenine ribonucleoside, tubercidin, by Streptomyces tubercidicus. The Journal of Biological Chemistry. 1967;242(12):2872-2876
93.Kónya A, Szabó Z, Láng I, Barta I, Salát J. Production of FK520 by Streptomyces tubercidicus. Microbiological Research. 2008;163(6):624-632. DOI: 10.1016/j.micres.2006.10.002
94.Ratti RP, Piza ACMT, Malpass AC, Hokka CO, Dubreuil JD, Sousa CP. Growing kinetics and antimicrobial activity of Streptomyces tubercidicus crude extracts. In: Microorganisms in Industry and Environment from Scientific and Industrial Research to Consumer Products. Vol. 1. Singapore: World Scientific Publishing Company Pvt Ltd. (Org.); 2010. pp. 589-592
95.Böttcher T, Kolodkin-Gal I, Kolter R, Losick R, Clardy J. Synthesis and activity of biomimetic biofilm disruptors. Journal of the American Chemical Society. 2013;135(8):2927-2930. DOI: 10.1021/ja3120955
96.Park SR, Tripathi A, Wu J, et al. Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway. Nature Communications. 2016;7:10710. Published: February 16, 2016. DOI: 10.1038/ncomms10710
97.Sharma D, Misba L, Khan AU. Antibiotics versus biofilm: An emerging battleground in microbial communities. Antimicrobial Resistance and Infection Control. 2019;8:76. Published: May 16, 2019. DOI: 10.1186/s13756-019-0533-3
98.Tamburini E, Mastromei G. Do bacterial cryptic genes really exist? Research in Microbiology. 2000;151(3):179-182. DOI: 10.1016/s0923-2508(00)00137-6
99.Onaka H. Novel antibiotic screening methods to awaken silent or cryptic secondary metabolic pathways in actinomycetes. Journal of Antibiotics (Tokyo). 2017;70(8):865-870. DOI: 10.1038/ja.2017.51
100.Chagas FO, Pupo MT. Chemical interaction of endophytic fungi and actinobacteria from Lychnophora ericoides in co-cultures. Microbiological Research. 2018;212-213:10-16. DOI: 10.1016/j.micres.2018.04.005
101.Onaka H, Mori Y, Igarashi Y, Furumai T. Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species. Applied and Environmental Microbiology. 2011;77(2):400-406. DOI: 10.1128/AEM.01337-10
102.Asamizu S, Ozaki T, Teramoto K, Satoh K, Onaka H. Killing of mycolic acid-containing bacteria aborted induction of antibiotic production by Streptomyces in combined-culture. PLoS One. 2015;10(11):e0142372. DOI: 10.1371/journal.pone.0142372
103.Romano S, Jackson SA, Patry S, Dobson ADW. Extending the “one strain many compounds” (OSMAC) principle to marine microorganisms. Marine Drugs. 2018;16(7):244. Published: July 23, 2018. DOI: 10.3390/md16070244
104.Falcinelli SD, Shi MC, Friedlander AM, Chua J. Green tea and epigallocatechin-3-gallate are bactericidal against Bacillus anthracis. FEMS Microbiology Letters. 2017;364(12). DOI: 10.1093/femsle/fnx127
105.Nogueira Cruz FP. Isolation of the Endophytic and Rhizospheric Microbiome Associated with Polygala Spp.: Evaluation of the Biotechnological Potential and Antimicrobial Activity. Thesis, Federal University of Sao Carlos; 2018
106.Breda CA, Gasperini AM, Garcia VL, et al. Phytochemical analysis and antifungal activity of extracts from leaves and fruit residues of Brazilian savanna plants aiming its use as safe fungicides. Natural Products and Bioprospecting. 2016;6(4):195-204. DOI: 10.1007/s13659-016-0101-y
107.Assis PC. Bactérias endofíticas isoladas de Caryocar brasiliense: atividade enzimática, antimicrobiana, leishimanicida e co-cultura com microrganismos patogênicos. Dissertation, Federal University of Sao Carlos; 2018
108.Naik BS. Developments in taxol production through endophytic fungal biotechnology: A review. Oriental Pharmacy and Experimental Medicine. 2019;19:1-13. DOI: 10.1007/s13596-018-0352-8
109.Paramanantham P, Pattnaik S, Siddhardha B. Natural products from endophytic fungi: Synthesis and applications. In: Singh BP, editor. Advances in Endophytic Fungal Research: Present Status and Future Challenges. Cham: Springer International Publishing; 2019. pp. 83-103. DOI: 10.1007/978-3-030-03589-1_5
110.Torres FL. Isolamento, caracterização e potencial biotecnológico de fungos endofíticos associados à plantas do Cerrado. Dissertation, Federal University of Sao Carlos; 2018
111.Carvalho CR, Gonçalves VN, Pereira CB, Johann S, Galliza IV, et al. The diversity, antimicrobial and anticancer activity of endophytic fungi associated with the medicinal plant Stryphnodendron adstringens (Mart.) Coville (Fabaceae) from the Brazilian savannah. Symbiosis. 2012;57:95-107
112.Loi M, Leonardis S, Mulè G, Logrieco AF, PC. A novel and potentially multifaceted dehydroascorbate reductase increasing the antioxidant systems is induced by beauvericinin tomato. Antioxidants (Basel). 2020;9(5):E435. Published: May 16, 2020. DOI: 10.3390/antiox9050435
113.Taevernier L, Veryser L, Roche N, et al. Human skin permeation of emerging mycotoxins (beauvericin and enniatins). Journal of Exposure Science & Environmental Epidemiology. 2016;26(3):277-287. DOI: 10.1038/jes.2015.10
114.Mallebrera B, Prosperini A, Font G, Ruiz MJ. In vitro mechanisms of beauvericin toxicity: A review. Food and Chemical Toxicology. 2018;111:537-545. DOI: 10.1016/j.fct.2017.11.019
115.Vega FE, Posada F, Peterson SW, Gianfagna TJ, Chaves F. Penicillium species endophytic in coffee plants and ochratoxin a production. Mycologia. 2006;98(1):31-42. DOI: 10.3852/mycologia.98.1.31
116.Mondani L, Palumbo R, Tsitsigiannis D, Perdikis D, Mazzoni E, Battilani P. Pest management and ochratoxin a contamination in grapes: A review. Toxins (Basel). 2020;12(5):E303. Published: May 7, 2020. DOI: 10.3390/toxins12050303
117.Pervaiz A, Khan R, Anwar F, Mushtaq G, Kamal MA, Khan H. Alkaloids: An emerging antibacterial modality against methicillin resistant Staphylococcus aureus. Current Pharmaceutical Design. 2016;22(28):4420-4429. DOI: 10.2174/1381612822999160629115627
118.Lakhundi S, Zhang K. Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology. Clinical Microbiology Reviews. 2018;31(4) e00020-18. Published: September 12, 2018. DOI: 10.1128/CMR.00020-18
119.Turner NA, Sharma-Kuinkel BK, Maskarinec SA, et al. Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research. Nature Reviews. Microbiology. 2019;17(4):203-218. DOI: 10.1038/s41579-018-0147-4
120.Newmister SA, Gober CM, Romminger S, et al. OxaD: A versatile indolic nitrone synthase from the marine-derived fungus Penicillium oxalicum F30. Journal of the American Chemical Society. 2016;138(35):11176-11184. DOI: 10.1021/jacs.6b04915
121.Qi X, Li X, Zhao J, et al. GKK1032C, a new alkaloid compound from the endophytic fungus Penicillium sp. CPCC 400817 with activity against methicillin-resistant S. aureus. Journal of Antibiotics (Tokyo). 2019;72(4):237-240. DOI: 10.1038/s41429-019-0144-5
122.Liu J, Yang X, He J, Xia M, Xu L, Yang S. Structure analysis of triterpene saponins in Polygala tenuifolia by electrospray ionization ion trap multiple-stage mass spectrometry. Journal of Mass Spectrometry. 2007;42(7):861-873. DOI: 10.1002/jms.1210
123.Tagousop CN, Tamokou JD, Kengne IC, Ngnokam D, Voutquenne-Nazabadioko L. Antimicrobial activities of saponins from Melanthera elliptica and their synergistic effects with antibiotics against pathogenic phenotypes. Chemistry Central Journal. 2018;12(1):97. Published: September 20, 2018. DOI: 10.1186/s13065-018-0466-6
124.Arabski M, Węgierek-Ciuk A, Czerwonka G, Lankoff A, Kaca W. Effects of saponins against clinical E. coli strains and eukaryotic cell line. Journal of Biomedicine & Biotechnology. 2012;2012:286216. DOI: 10.1155/2012/286216
125.Jin Z, Gao L, Zhang L, et al. Antimicrobial activity of saponins produced by two novel endophytic fungi from Panax notoginseng. Natural Product Research. 2017;31(22):2700-2703. DOI: 10.1080/14786419.2017.1292265
Written By
Felipe de Paula Nogueira Cruz, Andréa Cristina Bogas and Cristina Paiva de Sousa
Submitted: 14 April 2020Reviewed: 14 August 2020Published: 30 September 2020
Open access peer-reviewed chapter
