Composition and Biological Activities

Asmaa Missoum

Introduction

In 1928, Alexander Fleming discovered world’s first antibiotic penicillin, which revolutionized the class of anti-microbial drugs. Since then further antibiotics were discovered to treat infectious diseases (Debbab et al. 2010). However, due to bacteria developing resistance, new discoveries have never ceased and seeking more effective therapeutic drugs from natural products has become a challenge in the medicinal field (Berdy 2005). Research on chemistry of natural drugs is competitive with that of other synthetic products, as they are less toxic, biodegradable, and contribute to broad spectrum activities, even when administering lower quantities (Mossa et al. 2018). Nevertheless, research on natural products demands continuous enhancements in the screening process, which includes extraction, isolation, and metabolite structure interpretation. Such progress has provided the ability to conduct large number of bioassays, in high-throughput screening, with limited human intervention (Janardhan et al. 2014, Winn et al. 2018). This has also advocated a return to screening natural drug molecules, which continues to provide an important number of therapeutics approved for human use. Moreover, significant advances in synthetic biology, bioinformatics, and genomics can assist in altering natural products by biological and chemical means to boost their effectiveness (Selanra et al. 2014).

Interestingly, Streptowyces sp. are the key source for broad variety of biologically active compound, as they account for around 60% of the antibiotics discovered in 1990 and most of agriculturally important compounds. Since they are able to synthesize many classes of secondary' metabolites with diverse bioactivities, they are extensively used in research by academicians and industrialists (Raghava Rao et al. 2017). Tire biofunctional activities of these actinonrycetes may find application as antiviral, anticancer, antibiotics, and immunosuppressants, as well as agricultural

Pans-sud university, UFR Sciences, Г 5 Rue Georges Clemenceau, 91400 Orsay, France. Email: This email address is being protected from spam bots, you need Javascript enabled to view it agents such as insecticides, herbicides, and plant hormones. Nevertheless, other species of bacteria (.Bacillus, Pseudomonas and Nocardiopsis sp.) and fungi (Penicillium, Aspergillus, and Bipolaris sp ), whether soil-bome or endophytic, have also demonstrated similar effects from pure substances and extracts obtained from biomass or culture broth (Raekiansyah et al. 2017). Within this context, it would be nearly impossible to cover all topics related to biological activities’ investigation of the discovered natural products. Hence, this chapter will focus on bacterial and fungal bioactive molecules as components of extracts, and not as pure chemical substances. The reader is also referred to detailed findings from very recent studies, as well as proposed mechanisms of action that contribute to these bioactivities.

Anti-microbial agents

Antibacterial agents

Bacterial genera with a high chance to detect compounds of interest as biosources are reported to be Actinonivcetes, Bacilli, and Pseudomonads (Berdy 2005). Recently, many pharmaceutically significant antibiotics have been identified from these bioresources: factumyciu and tetrangomycin produced by Streptoniyces globosus DK15 and Streptoniyces ederensis ST 13 isolated from forest soils located in Vietnam (Charousova et al. 2018), Bagremycins F and G produced by marine-derived Streptoniyces sp. ZZ745 (Zhang et al. 2018), and Anthracimyciu В collected from Deep-Sea Streptoniyces cyaneofuscatus M-169 cultures (Rodriguez et al. 2018). Other Streptoniyces species such as Streptoniyces levis, isolated from soil sample of north India, were proven to be effective against Gram negative bacteria (Singh et al. 2018). Besides, non-proteiuaceous and heat-stable bioactive components of Streptoniyces sp. SBT343 such as azalomycin, actiuoramide D, and azamerone, derived from marine sponges, inhibited staphylococcal biofilm formation without affecting bacterial viability. Nevertheless, these properties make them good candidates for developing future therapies against contact lens-mediated ocular infections (Balasubramanian et al. 2017).

Bacteriociu isolated from soil Bacillus subtilis GAS 101 has been reported to have proteinaceous namre and was able to disrupt the bacterial cell membrane as its mechanism of action. These are produced by ribosomes and secreted by bacteria, mainly Bacillus, for self-defense (Sliamia et al. 2018). Soil Bacillus species isolated from Tunisian arid areas also harbors high inhibitory potentials against clinical isolates of Gram negative bacteria. The identified active component was identified as 1-acetyl-p-carboline (Nasfi et al. 2018). Nevertheless, various other research groups including our university laboratory have also been responsible for screening studies. Many different Bacillus species, derived from Qatari coastal soils, have demonstrated significant antimicrobial activities against Staphylococcus aureus, Staphylococcus epidermis, and Escherichia coli. Unfortunately, the potent bioactive metabolites were not characterized in this study (Missoum and Al-Tliaui 2017). Nevertheless, significant biomolecules with antibacterial activities are presented in Fig. 1.

Most interestingly, different chemical compounds from marine-derived fungus Aspergillus sp. scs-kfd66 inhibited the growth of pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes (An et al.

Examples of antibacterial compounds and their structures (Nasfi et al. 2018, Charousova et al. 201S, Zhang et al. 201S, Cheng et al. 201S)

Fig. 1. Examples of antibacterial compounds and their structures (Nasfi et al. 2018, Charousova et al. 201S, Zhang et al. 201S, Cheng et al. 201S).

2018). The genus Penicillium, which is one of the most recognized genera of fungi for the discovery of bioactive constitutes, remains to provide major antibacterial drugs. In fact, newly discovered Famesylcycloliexenones as Peuiginsengins B-E, isolated from Deep Sea-derived Penicillium sp. YPGA11, exhibited similar promising effects (Cheng et al. 2018).

Antifungal agents

Fungal infections can be divided into two categories, systematic mycosis or dermatomycosis. The former is often lethal and has attracted more attention in recent research of mycology due to etiological changes, which mainly has occurred as a result of using broad spectrum antibacterial therapies. Consequently, opportunistic infections with fungi such as Candida sp. have increased gradually. These are also more prominent in immuno-compromised and intensive care unit patients (Srivastava and Dubey 2016, Cordova-Davalos et al. 2018). Most of the important antimicrobial compounds including those having antifungal bioactivities are summarized in Table 1.

It was reported for the first time that uncharacterized biomolecules from Streptoniyces chrestomyceticus ADP4 inhibited various Candida albicans strain at MIC90 values ranging from to 3.70 ± 1.8 to 10.10 ± 2.6 pg/tnL. Other strains such as Candida krusei, Candida tropicalis, and Candida paripsilosis were also inhibited but had higher MIC90 values. Scanning electron microscopic (SEM) studies showed

Table 1. Summary of recently isolated bioactive compounds and then antunicrobial activities.

Bioactive compound

Microorganism/

producer

Source

Biological

activities

Reference

Factumycm,

Tetrangomycin

Streptomyces globosiis DK15, Streptomyces ederensis ST13

Forest soils located in Vietnam

Antibacterial

(Charousova et al. 2018)

Bagremycms F and G

Streptomyces sp. ZZ74S

Mamie

(Zhang et al. 2018)

Anthracunycin В

Streptomyces cyaneofuscatus M-169

Deep-Sea

(Rodriguez et al 2018)

Bactenocm

Bacillus subtilis GAS101

Sod

(Shanna et al. 2018)

1 -acetyl-p-cai'bolme Bacillomycm and Fengycm

Bacillus species

Tunisian and areas

(Nasfi et al. 2018)

Penigmsengms B-E

Penicillium sp. YPGA11

Deep-Sea

(Cheng et al. 2018)

Emericellipsin A

Emericellopsis alkaliua

Alkaline soil near Zheltyr Lake, Russia

Antifungal

(Rogozhm et al. 2018)

PI 8 peptide

Bacillus subtilis

Antiviral

(Starosila et al. 2017)

Hydroxy marilone C

Streptomyces badius

Egyptian soils

Antiviral,

anti-cancer

(El Sayed et al. 2016)

Butenolide

Streptomyces sp. Smu03

Elephas maximus intestines

Antiviral

(Li et al, 2018)

BrefeldinA

Penicillium sp. FKI-7127

(Raekiansyah et al. 2017)

Xanthones

Aspergillus iizukae

Coastal salme soil

(Kauget al. 2018)

Proteins and carbohydrates

Trichoderma viride

Cucumber rhizosphere soil

(Awad et al. 2018)

Polyketides

Streptomyces sp. USC-16018

Mamie

Antiparasitic

(Buedenbender et al. 2018)

Cyclodepsipeptide WS9326A and annunycin

Streptomyces asterosporus DSM 41452

(Zhang et al. 2017a)

Gaucidm W

Streptomyces SUK.10

Shorea ovalis trees

(Zm et al. 2017)

10-acetyl trichoderonic acid A, hydroheptelidic acid, and 6’-acetoxy- pilifomnc acid

Nectria pseudotrichia

Caesalpmia

echinata

(Costa et al. 2018)

that the metabolites extract inhibited biofilm formation by disturbing cell membrane as well as preventing fungal cells from adhering to polystyrene surface and their conversion to the hyphal status (Srivastava et al. 2016). Bioactive constitutes from Streptomyces species also showed anti-biofilm activity in C. albican. At 2 gL'1 concentration, Streptomyces toxytricini Fz94 isolated from Egyptian soils gave 92% inhibition compared to 90% by Ketoconazole after 120 min (Sheir and Hafez 2017), while bioactive extracts produced by soil Streptomyces sp. GCAL-25 were three tunes more effective than the control fungicide, amphotericin В (Cordova-Davalos et al. 2018). Further studies are required to purify these specific compounds and elucidate then structures.

Highly stable AFPprotein secreted from Aspergillus giganteus selectively inhibits the growth of filamentous fungi without affecting the mammalian cells’ viability. Their у-core motif is known to destabilize the integrity of plasma membranes. In a recent study, molecular dynamics simulations and NMR spectroscopy were used to characterize the dynamical behavior of AFP with fungal model membranes in solution. It was also concluded that AFP protein does not destroy the fungal membrane integrity by pore formation but covers its surface using a multistep mechanism (Utesch et al. 2018). Other fungal peptides such as emericellipsin A isolated from an extrenroplrile, Emericellopsis alkalina, inhibited the growth of all Candida species as well as filamentous fungi A. fumigatus KBP F24 and A. niger ATCC 16404 at a concentration of 40 pg/per disc (Rogozlrin et al. 2018).

Antiviral agents

The major targets for antiviral chemotherapy are herpes, influenza, and hitman immunodeficiency virus (HTV). To fight viral infections, clinical drugs should inhibit the virus replication at certain concentrations without harming the host cells. Although the success rate of antiviral therapy is still far away from that of antibacterial therapy, the situation is progr essing. In recent years, a number of new biomolecules have been found to be effective against a variety of viruses (Fig. 2).

PI8 is a new peptide that was recently isolated from the probiotic strain of Bacillus subtilis. This has resulted in complete inhibition of the influenza virus at 12.5 to 100 g/ml concentrations. P18 demonstrated no toxic effect in cytotoxicity studies involving Madin-Darby canine kidney (MDCK) cells (Starosila et al. 2017). Besides, hydroxy marilone C produced by Streptomyces badius isolated from Egyptian soil, protected 50% of the virus-infected MDCK cells against H1N1 cytopathogenicity (ECJ0) by 33.25% for 80 pg/rnl. However, the maximum cytotoxicity was at 27.9% with IC50 value of 128.1 gg/ml (El Sayed et al. 2016). Buteuolide produced by Streptomyces sp. Snru03 obtained from Elephas maximis intestines was also shown to be effective against oseltamivir-resistant influenza A virus strain A/PR/8/34 at early stages of infection. It is suggested that this molecule may have interfered with the fusogenic process of hemagglutmin (HA) of the virus, thus blocking its entry into host cells (Li et al. 2018).

118 Microbial Systematics: Taxonomy, Microbial Ecology Diversify

Examples of antifungal and antiviral compounds and then structures (Raekiansyah et al. 2017, Li et al. 2018, El Sayed et al. 2016, Awad et al. 2018)

Fig. 2. Examples of antifungal and antiviral compounds and then structures (Raekiansyah et al. 2017, Li et al. 2018, El Sayed et al. 2016, Awad et al. 2018).

On the other hand, novel derived brefeldin A derived from Pemcillium sp. FKI-7127 demonstrated significant inhibitory effects against different serotypes of dengue viruses as well as Zika and Japanese encephalitis viruses. The former is a mosquito-bome pathogen that causes dengue fever affecting 390 million people per year (Raekiansyah et al. 2017). Moreover, xanthones were extracted for the first time from Aspergillus iizukae fungus isolated from coastal saline soil. These compounds showed strong activities towards influenza virus H1N1, herpes simplex virus types 1 and 2 with respective IC50 values of 44.6, 21.4, and 76.7 pM (Kang et al. 2018). Proteins and carbohydrates from cucumber rhizosphere soil-derived fungus, Trichoderma viride, showed a moderate antiviral activity of 20% and 18%, respectively, against H5N1 virus at a concentration of 25 pg/pl (Awad et al. 2018).

Antiparasitic agents

Various parasitic diseases caused by protozoa and helminths invading the human body and domestic annuals surely represent a major public health problem, particularly in tropical regions of the world. Among these diseases, malaria results in more than 400.000 deaths yearly. Plasmodium protozoan parasites that cause this vector-bome disease, use Anopheles mosquitos as the main host to spread it through human populations (Buedenbeuder et al. 2018). The emergence of parasites’ resistance to currently commercially available drugs is one of the key factors that lead to infecting billions of people. Hence, new bioactive molecules are needed in order to reduce the risk of resistance and combat the spread of malaria as well as other parasitic diseases (Zinet al. 2017).

Polyketides isolated from marine-derived Streptomyces sp. USC-16018 demonstrated an inhibition of > 75% against Plasmodium falciparum strains, which was brought about through many mutations’ types and have become resistant to nearly all antimalarial treatments including chloroquine (Buedenbeuder et al. 2018). Similarly, novel cyclodepsipeptide WS9326A and polyketide annimycin derivatives produced by Streptomyces asterosporns DSM 41452 exhibited modest inhibitory activity against P falciparum, compared to its engineered mutant which yielded better results (Zhang et al. 2017). Gancidin W is another antimalarial agent isolated from Streptomyces SUK10, an endophytic to Shorea ovalis trees. This strain exhibited an in vivo inhibition rate of 80% against Plasmodium berghei PZZ1/100 with a very low toxicity (Zin et al. 2017).

Protozoan species of the genus Leislmiania are also transmitted by the bites of infected female plilebotomiue sandflies, affecting human populations in the Americas with an incidence rate of 19.76 cases per 100,000 inhabitants. Anhydrocochlioquinone A is a novel leishmauicidal that was recently isolated from the fungus Cochliobolus sp. Its ethyl acetate extract was shown to demonstrate 78% inhibition against Leishmauia amazonensis amastigotes with an EC50 value of 22 lg/mL (42.7 1M) in the in vitro assay (Campos et al. 2017). Another endophytic fungus, Nectria pseudotrichia, isolated from Caesalpinia echinata has shown antiparasitical activity against Leishmauia (Viannia) braziliensis with a potential low toxicity to THP-1 cells. Fractionation of the extract yielded 10-acetyl triclioderonic acid A, hydroheptelidic acid, and 6’-acetoxy-piliformic acid, which were the most active compounds with ICJ0 values of 21.4, 24.8, and 28.3 pM, respectively (Costa et al. 2018). Moreover, fungi species isolated from mangroves in Florida inhibited Naegleria fowleri, a brain-eating amoeba, by > 67% at 50 pg/mL (Demers et al. 2018).

 
Source
< Prev   CONTENTS   Source   Next >