Molecular docking, molecular dynamics simulations and binding free energy studies of interactions between Mycobacterium tuberculosis Pks13, PknG and bioactive constituents of extremophilic bacteria.

Mycobacterial pathogens present a significant challenge to disease control efforts globally due to their inherent resistance to multiple antibiotics. The rise of drug-resistant strains of Mycobacterium tuberculosis has prompted an urgent need for innovative therapeutic solutions. One promising way to discover new tuberculosis drugs is by utilizing natural products from the vast biochemical space. Multidisciplinary methods can used to harness the bioactivity of these natural products. This study aimed to evaluate the antimycobacterial efficacy of functional crude extracts from bacteria isolated from gold mine tailings in South Africa. Bacterial strains were identified using 16S rRNA sequencing. The crude extracts obtained from the bacteria were tested against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155, and Mycobacterium aurum A+. Untargeted HPLC-qTOF and molecular networking were used to identify the functional constituents present in extracts that exhibited inhibitory activity. A virtual screening workflow (VSW) was used to filter compounds that were strong binders to Mycobacterium tuberculosis Pks13 and PknG. The ligands returned from the VSW were subjected to optimization using density functional theory (DFT) at M06-2X/6-311++ (d,p) level of theory and basis set implemented in Gaussian16 Rev.C01. The optimized ligands were re-docked against Mycobacterium tuberculosis Pks13 and PknG. Molecular dynamics simulation and molecular mechanics generalized born surface area were used to evaluate the stability of the protein-ligand complexes formed by the identified hits. The hit that showed promising binding characteristics was virtually modified through multiple synthetic routes using reaction-driven enumeration. Three bacterial isolates showed significant activity against the two strains of Mycobacterium, while only two, Bacillus subtilis and Bacillus licheniformis, exhibited activity against both Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155, and Mycobacterium aurum A+. The tentatively identified compounds from the bacterial crude extracts belonged to various classes of natural compounds associated with antimicrobial activity. Two compounds, cyclo-(L-Pro-4-OH-L-Leu) and vazabitide A, showed strong binding against PknG and Pks13, with pre-MD MM-GBSA values of - 42.8 kcal/mol and - 47.6 kcal/mol, respectively. The DFT-optimized compounds exhibited the same docking scores as the ligands optimized using the OPSL-4 force field. After modifying vazabitide A, its affinity to the Pks13 binding site increased to - 85.8 kcal/mol, as revealed by the post-MD MM-GBSA analysis. This study highlights the potential of bacteria isolates from gold mine tailings as a source of new scaffolds for designing and optimizing anti-Mycobacterium agents. These agents synthesized in-silico can be further tested in-vitro to evaluate their efficacy.

In-silico and in-vitro assessments of some fabaceae, rhamnaceae, apocynaceae, and anacardiaceae species against Mycobacterium tuberculosis H37Rv and triple-negative breast cancer cells.

Medicinal plants play a huge role in the treatment of various diseases in the Limpopo province (South Africa). Traditionally, concoctions used for treating tuberculosis and cancer are sometimes prepared from plant parts naturally occurring in the region, these include (but not limited to) Schotia brachypetala, Rauvolfia caffra, Schinus molle, Ziziphus mucronate, and Senna petersiana. In this study, the aim was to evaluate the potential antimycobacterial activity of the five medicinal plants against Mycobacterium smegmatis mc2155, Mycobacterium aurum A + , and Mycobacterium tuberculosis H37Rv, and cytotoxic activity against MDA-MB 231 triple-negative breast cancer cells. Phytochemical constituents present in R. caffra and S. molle were tentatively identified by LC-QTOF-MS/MS as these extracts showed antimycobacterial and cytotoxic activity. A rigorous Virtual Screening Workflow (VSW) of the tentatively identified phytocompounds was then employed to identify potential inhibitor/s of M. tuberculosis pantothenate kinase (PanK). Molecular dynamics simulations and post-MM-GBSA free energy calculations were used to determine the potential mode of action and selectivity of selected phytocompounds. The results showed that plant crude extracts generally exhibited poor antimycobacterial activity, except for R. caffra and S. molle which exhibited average efficacy against M. tuberculosis H37Rv with minimum inhibitory concentrations between 0.25-0.125 mg/mL. Only one compound with a favourable ADME profile, namely, norajmaline was returned from the VSW. Norajmaline exhibited a docking score of -7.47 kcal/mol, while, pre-MM-GBSA calculation revealed binding free energy to be -37.64 kcal/mol. All plant extracts exhibited a 50% inhibitory concentration (IC50) of < 30 µg/mL against MDA-MB 231 cells. Flow cytometry analysis of treated MDA-MB 231 cells showed that the dichloromethane extracts from S. petersiana, Z. mucronate, and ethyl acetate extracts from R. caffra and S. molle induced higher levels of apoptosis than cisplatin. It was concluded that norajmaline could emerge as a potential antimycobacterial lead compound. Validation of the antimycobacterial activity of norajmaline will need to be performed in vitro and in vivo before chemical modifications to enhance potency and efficacy are done. S. petersiana, Z. mucronate, R.caffra and S. molle possess strong potential as key contributors in developing new and effective treatments for triple-negative breast cancer in light of the urgent requirement for innovative therapeutic solutions.

Antimycobacterial activity and molecular docking of methanolic extracts and compounds of marine fungi from Saldanha and False Bays, South Africa.

The number and diversity of drugs in the tuberculosis (TB) drug development process has increased over the years, yet the attrition rate remains very high, signaling the need for continued research in drug discovery. In this study, crude secondary metabolites from marine fungi associated with ascidians collected from Saldanha and False Bays (South Africa) were investigated for antimycobacterial activity. Isolation of fungi was performed by sectioning thin inner-tissues of ascidians and spreading them over potato dextrose agar (PDA). Solid state fermentation of fungal isolates on PDA was then performed for 28 days to allow production of secondary metabolites. Afterwards, PDA cultures were dried and solid-liquid extraction using methanol was performed to extract fungal metabolites. Profiling of metabolites was performed using untargeted liquid chromatography quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The broth microdilution method was used to determine antimycobacterial activity against Mycobacterium smegmatis mc2155 and Mycobacterium tuberculosis H37Rv, while in silico flexible docking was performed on selected target proteins from M. tuberculosis. A total of 16 ascidians were sampled and 46 fungi were isolated. Only 32 fungal isolates were sequenced, and their sequences submitted to GenBank to obtain accession numbers. Metabolite profiling of 6 selected fungal extracts resulted in the identification of 65 metabolites. The most interesting extract was that of Clonostachys rogersoniana MGK33 which inhibited Mycobacterium smegmatis mc2155 and Mycobacterium tuberculosis H37Rv growth with minimum inhibitory concentrations (MICs) of 0.125 and 0.2 mg/mL, respectively. These results were in accordance with those from in silico molecular docking studies which showed that bionectin F produced by C. rogersoniana MGK33 is a potential inhibitor of M. tuberculosis ß-ketoacyl-acyl carrier protein reductase (MabA, PDB ID = 1UZN), with the docking score observed as -11.17 kcal/mol. These findings provided evidence to conclude that metabolites from marine-derived fungi are potential sources of bioactive metabolites with antimycobacterial activity. Even though in silico studies showed that bionectin F is a potent inhibitor of an essential enzyme, MabA, the results should be validated by performing purification of bionectin F from C. rogersoniana MGK33 and in vitro assays against MabA and whole cells (M. tuberculosis).

Draft Whole-Genome Sequence of Penicillium simplicissimum A4, a Putative Endophyte from Echium plantagineum.

We report the draft whole-genome sequence of the putative endophytic fungus Penicillium simplicissimum A4, isolated from the roots of Echium plantagineum plants. The genome was sequenced using PacBio technology with an estimated genome size of 39 Mb.

Biofertilizer: The Future of Food Security and Food Safety.

There is a direct correlation between population growth and food demand. As the global population continues to rise, there is a need to scale up food production to meet the food demand of the population. In addition, the arable land over time has lost its naturally endowed nutrients. Hence, alternative measures such as fertilizers, pesticides, and herbicides are used to fortify the soil and scale up the production rate. As efforts are being made to meet this food demand and ensure food security, it is equally important to ensure food safety for consumption. Food safety measures need to be put in place throughout the food production chain lines. One of the fundamental measures is the use of biofertilizers or plant growth promoters instead of chemical or synthesized fertilizers, pesticides, and herbicides that poise several dangers to human and animal health. Biofertilizers competitively colonize plant root systems, which, in turn, enhance nutrient uptake, increase productivity and crop yield, improve plants' tolerance to stress and their resistance to pathogens, and improve plant growth through mechanisms such as the mobilization of essential elements, nutrients, and plant growth hormones. Biofertilizers are cost-effective and ecofriendly in nature, and their continuous usage enhances soil fertility. They also increase crop yield by up to about 10-40% by increasing protein contents, essential amino acids, and vitamins, and by nitrogen fixation. This review therefore highlighted different types of biofertilizers and the mechanisms by which they elicit their function to enhance crop yield to meet food demand. In addition, the review also addressed the role of microorganisms in promoting plant growth and the various organisms that are beneficial for enhancing plant growth.

Effectiveness of the Novel Anti-TB Bedaquiline against Drug-Resistant TB in Africa: A Systematic Review of the Literature.

BACKGROUND: In 2018, an estimated 10.0 million people contracted tuberculosis (TB), and 1.5 million died from it, including 1.25 million HIV-negative persons and 251,000 HIV-associated TB fatalities. Drug-resistant tuberculosis (DR-TB) is an important contributor to global TB mortality. Multi-drug-resistant TB (MDR-TB) is defined as TB resistant to at least isoniazid (INH) and rifampin (RMP), which are recommended by the WHO as essential drugs for treatment. OBJECTIVE: To investigate the effectiveness of bedaquiline addition to the treatment of drug-resistant TB infections on the African continent. METHODOLOGY: The search engine databases Medline, PubMed, Google Scholar, and Embase were used to obtain published data pertaining to DR-TB between 2012 and 2021 in Africa. Included studies had to document clinical characteristics at treatment initiation and outcomes at the end of treatment (i.e., success, failure, recurrence, loss to follow-up, and death). The included studies were used to conduct a meta-analysis. All data analysis and visualization were performed using the R programming environment. The log risk ratios and sample variances were calculated for DR-TB patients treated with BBQ monotherapy vs. BDQ and other drug therapy. To quantify heterogeneity among the included studies, random effect sizes were calculated. RESULTS: A total of 16 studies in Africa from Mozambique (N = 1 study), Eswatini (N = 1 study), Democratic Republic of the Congo (N = 1 study), South Africa (N = 12 studies), and a multicenter study undertaken across Africa (N = 1 study) were included. In total, 22,368 individuals participated in the research studies. Among the patients, (55.2%; 12,350/22,368) were male while 9723/22,368 (44%) were female. Overall, (9%; 2033/22,368) of patients received BDQ monotherapy, while (88%; 19,630/22,368) patients received bedaquiline combined with other antibiotics. In total, (42%; 9465/22,368) of the patients were successfully treated. About (39%; 8653/22,368) of participants finished their therapy, meanwhile (5%; 1166/22,368) did not finish their therapy, while people (0.4%; 99/22,368) were lost to follow up. A total of (42%; 9265/22,368) patients died. CONCLUSION: Very few studies on bedaquiline usage in DR-TB in Africa have been published to date. Bedaquiline has been shown to enhance DR-TB results in clinical studies and programmatic settings. Hence, the World Health Organization (WHO) has recommended that it be included in DR-TB regimens. However, in the current study limited improvement to DR-TB treatment results were observed using BDQ on the continent. Better in-country monitoring and reporting, as well as multi-country collaborative cohort studies of DR-TB, can expand the knowledge of bedaquiline usage and clinical impact, as well as the risks and benefits throughout the continent.

Biosynthesis of Smaller-Sized Platinum Nanoparticles Using the Leaf Extract of Combretum erythrophyllum and Its Antibacterial Activities.

Nanobiotechnology is a promising field in the development of safe antibiotics to combat the increasing trend of antibiotic resistance. Nature is a vast reservoir for green materials used in the synthesis of non-toxic and environmentally friendly nano-antibiotics. We present for the first time a facile, green, cost-effective, plant-mediated synthesis of platinum nanoparticles (PtNPs) using the extract of Combretum erythrophyllum (CE) plant leaves. The extract of CE served as both a bio-reductant and a stabilizing agent. The as-synthesized PtNPs were characterized using ultraviolet-visible (UV-Vis) absorption spectroscopy, high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and dynamic light scattering (DLS) techniques. The HR-TEM image confirmed that the PtNPs are ultrasmall, spherical, and well dispersed with an average particle diameter of 1.04 ± 0.26 nm. The PtNPs showed strong antibacterial activities against pathogenic Gram-positive Staphylococcus epidermidis (ATCC 14990) at a minimum inhibitory concentration (MIC) of 3.125 µg/mL and Gram-negative Klebsiella oxytoca (ATCC 8724) and Klebsiella aerogenes (ATCC 27853) at an MIC value of 1.56 µg/mL. The CE-stabilized PtNPs was mostly effective in Klebsiella species that are causative organisms in nosocomial infections.

Hydrothermal Processing and In Vitro Simulated Human Digestion Affects the Bioaccessibility and Bioactivity of Phenolic Compounds in African Pumpkin (Momordica balsamina) Leaves.

The African pumpkin (Momordica balsamina) contains bioactive phenolic compounds that may assist in reducing oxidative stress in the human body. The leaves are mainly consumed after boiling in water for a specific time; this hydrothermal process and conditions of the gastrointestinal tract may affect the presence and bioactivity of phenolics either positively or negatively. In this study, the effects of hydrothermal processing (boiling) and in vitro simulated human digestion on the phenolic composition, bioaccessibility and bioactivity in African pumpkin were investigated in comparison with those of spinach (Spinacia oleracea). A high-resolution ultra-performance liquid chromatography, coupled with diode array detection, quadrupole time-of-flight and mass spectrometer (UPLC-DAD-QTOF-MS) was used to profile phenolic metabolites. Metabolites such as 3-caffeoylquinic acid, 5-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid were highly concentrated in the boiled vegetable extracts compared to the raw undigested and all digested samples. The majority of African pumpkin and spinach extracts (non-digested and digested) protected Deoxyribonucleic acid (DNA), (mouse fibroblast) L929 and human epithelial colorectal adenocarcinoma (Caco-2) cells from 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative damage. From these results, the consumption of boiled African pumpkin leaves, as well as spinach, could be encouraged, as bioactive metabolites present may reduce oxidative stress in the body.

Facile Green, Room-Temperature Synthesis of Gold Nanoparticles Using Combretum erythrophyllum Leaf Extract: Antibacterial and Cell Viability Studies against Normal and Cancerous Cells.

We herein report a facile, green, cost-effective, plant-mediated synthesis of gold nanoparticles (AuNPs) for the first time using Combretum erythrophyllum (CE) plant leaves. The synthesis was conducted at room temperature using CE leaf extract serving as a reducing and capping agent. The as-synthesized AuNPs were found to be crystalline, well dispersed, and spherical in shape with an average diameter of 13.20 nm and an excellent stability of over 60 days. The AuNPs showed broad-spectrum antibacterial activities against both pathogenic Gram-positive (Staphylococcus epidermidis (ATCC14990), Staphylococcus aureus (ATCC 25923), Mycobacterium smegmatis (MC 215)) and Gram-negative bacteria (Proteus mirabilis (ATCC 7002), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13822), Klebsiella oxytoca (ATCC 8724)), with a minimum inhibition concentration of 62.5 µg/mL. In addition, the as-synthesized AuNPs were highly stable with exceptional cell viability towards normal cells (BHK- 21) and cancerous cancer cell lines (cervical and lung cancer).

The Relationship between Cadmium Toxicity and the Modulation of Epigenetic Traits in Plants.

Elevated concentrations of heavy metals such as cadmium (Cd) have a negative impact on staple crop production due to their ability to elicit cytotoxic and genotoxic effects on plants. In order to understand the relationship between Cd stress and plants in an effort to improve Cd tolerance, studies have identified genetic mechanisms which could be important for conferring stress tolerance. In recent years epigenetic studies have garnered much attention and hold great potential in both improving the understanding of Cd stress in plants as well as revealing candidate mechanisms for future work. This review describes some of the main epigenetic mechanisms involved in Cd stress responses. We summarize recent literature and data pertaining to chromatin remodeling, DNA methylation, histone acetylation and miRNAs in order to understand the role these epigenetic traits play in cadmium tolerance. The review aims to provide the framework for future studies where these epigenetic traits may be used in plant breeding and molecular studies in order to improve Cd tolerance.

Genomic and Physiological Investigation of Heavy Metal Resistance from Plant Endophytic Methylobacterium radiotolerans MAMP 4754, Isolated from Combretum erythrophyllum.

Combretum erythrophyllum is an indigenous southern African tree species, a metal hyperaccumulator that has been used as a phytoextraction option for tailing dams in Johannesburg, South Africa. In hyperaccumulators, metal detoxification has also been linked or attributed to the activities of endophytes, and, in this regard, metal detoxification can be considered a form of endophytic behavior. Therefore, we report herein on the identification of proteins that confer heavy metal resistance, the in vitro characterization of heavy metal resistance, and the production of plant growth-promoting (PGP) volatiles by Methylobacterium radiotolerans MAMP 4754. Multigenome comparative analyses of M. radiotolerans MAMP 4754 against eight other endophytic strains led to the identification of zinc, copper, and nickel resistance proteins in the genome of this endophyte. The maximum tolerance concentration (MTC) of this strain towards these metals was also investigated. The metal-exposed cells were analyzed by transmission electron microscopy (TEM). The ethyl acetate and chloroform extracts (1:1 v/v) of heavy metal untreated M. radiotolerans MAMP 4754 were also screened for the production of PGP compounds by Gas Chromatography-Mass Spectroscopy (GC/MS). The MTC was recorded at 15 mM, 4 mM, and 12 mM for zinc, copper, and nickel, respectively. The TEM analysis showed the accumulation of metals in the intracellular environment of M. radiotolerans MAMP 4754, while the GC/MS analysis revealed several plant growth-promoting compounds, including alcohols, phthalate esters, alkenes, ketones, sulfide derivatives, phenols, and thiazoles. Our findings suggest that the genetic makeup of M. radiotolerans MAMP 4754 encodes heavy metal resistant proteins that indicate hyperaccumulator-specific endophytic behavior and the potential for application in bioremediation. The production of plant growth-promoting volatiles in pure culture by M. raditotolerans MAMP 4754 is a characteristic feature for plant growth-promoting bacteria.

Toxic Metal Implications on Agricultural Soils, Plants, Animals, Aquatic life and Human Health.

The problem of environmental pollution is a global concern as it affects the entire ecosystem. There is a cyclic revolution of pollutants from industrial waste or anthropogenic sources into the environment, farmlands, plants, livestock and subsequently humans through the food chain. Most of the toxic metal cases in Africa and other developing nations are a result of industrialization coupled with poor effluent disposal and management. Due to widespread mining activities in South Africa, pollution is a common site with devastating consequences on the health of animals and humans likewise. In recent years, talks on toxic metal pollution had taken center stage in most scientific symposiums as a serious health concern. Very high levels of toxic metals have been reported in most parts of South African soils, plants, animals and water bodies due to pollution. Toxic metals such as Zinc (Zn), Lead (Pb), Aluminium (Al), Cadmium (Cd), Nickel (Ni), Iron (Fe), Manganese (Mn) and Arsenic (As) are major mining effluents from tailings which contaminate both the surface and underground water, soil and food, thus affecting biological function, endocrine systems and growth. Environmental toxicity in livestock is traceable to pesticides, agrochemicals and toxic metals. In this review, concerted efforts were made to condense the information contained in literature regarding toxic metal pollution and its implications in soil, water, plants, animals, marine life and human health.

Antimicrobial and Antioxidant Properties of a Bacterial Endophyte, Methylobacterium radiotolerans MAMP 4754, Isolated from Combretum erythrophyllum Seeds.

This study reports on the isolation and identification of Methylobacterium radiotolerans MAMP 4754 from the seeds of the medicinal plant, Combretum erythrophyllum, for the purposes of investigating antimicrobial and antioxidant activities from this endophyte. The strain identity was confirmed by 16S rRNA-based phylogeny and Scanning Electron Microscopy (SEM). Ethyl acetate and chloroform (1 : 1 v/v) extracts from the endophyte were tested for antimicrobial and antioxidant activity on a total of 7 bacterial species (3 Gram-positive and 4 Gram-negative) using the standard Minimum Inhibitory Concentration (MIC) protocol and Quantitative Radical Scavenging activity using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay, respectively. The MICs were recorded at 250 µg/mL for B. subtilis ATCC 19659, B. cereus ATCC 1076, E. coli ATCC1053, and 62.5 µg/mL for K. oxytoca ATCC 13182 and M. smegmatis ATCC 21293, while an IC50 of 5.65 µg/mL was recorded with the DPPH assay. Qualitative phytochemical analysis was positive for alkaloids, flavonoids, and steroids. Gas chromatography/mass spectrometry (GC/MS) analysis revealed the presence of 9-octadecene, 2,4-dinitrophenyl acetate, and 2(5H)-furanone, which have been previously reported for the targeted activities. M. radiotolerans MAMP 4754 tested positive for antimicrobial and antioxidant activity and this is linked to the production of plant-derived secondary metabolites by this strain.

Large-Scale Screening of 239 Traditional Chinese Medicinal Plant Extracts for Their Antibacterial Activities against Multidrug-Resistant Staphylococcus aureus and Cytotoxic Activities.

Novel alternative antibacterial compounds have been persistently explored from plants as natural sources to overcome antibiotic resistance leading to serious foodborne bacterial illnesses. In this study, the ethanolic extracts from 239 traditional Chinese medicinal plants (TCMP)' materials were screened to discover promising candidates that have strong antibacterial properties against multidrug-resistant Staphylococcus (S.) aureus and low cytotoxicity. The results revealed that 74 extracts exhibited good antibacterial activities (diameter of inhibition zone (DIZ) ≥ 15 mm). Furthermore, 18 extracts (DIZ ≥ 20 mm) were determined their minimum inhibitory concentrations (MIC) and minimum bactericide concentrations (MBC), ranging from 0.1 to 12.5 mg/mL and 0.78 to 25 mg/mL, respectively. In addition, most of the 18 extracts showed relatively low cytotoxicity (a median lethal concentration (LC50) >100 µg/mL). The 18 extracts were further determined to estimate possible correlation of their phenolic contents with antibacterial activity, and the results did not show any significant correlation. In conclusion, this study selected out some promising antibacterial TCMP extracts with low cytotoxicity, including Rhus chinensis Mill., Ilex rotunda Thunb., Leontice kiangnanensis P.L.Chiu, Oroxylum indicum Vent., Isatis tinctorial L., Terminalia chebula Retz., Acacia catechu (L.f.) Willd., Spatholobus suberectus Dunn, Rabdosia rubescens (Hemsl.) H.Hara, Salvia miltiorrhiza Bunge, Fraxinus fallax Lingelsh, Coptis chinensis Franch., Agrimonia Pilosa Ledeb., and Phellodendron chinense C.K.Schneid.

Diversity and Antimicrobial Activity of Culturable Fungal Endophytes in Solanum mauritianum.

Plant endophytes are microbial sources of bioactive secondary metabolites, which mimic the natural compounds chemistry of their respective host plants in a similar manner. This study explored the isolation and identification of fungal endophytes, and investigated the antibacterial and antimycobacterial activity of their crude extracts. Fungal endophytes were isolated from Solanum mauritianum, identified using morphological traits and internal transcribed spacer ribosomal-deoxyribonucleic acid (ITS-rDNA) sequence analysis. Eight fungal endophytes were identified as Aureobasidium pullulans, Paracamarosporium leucadendri, Cladosporium sp., Collectotrichum boninense, Fusarium sp., Hyalodendriella sp., and Talaromyces sp., while Penicillium chrysogenum was isolated from the leaves and unripe fruits. Good activity was observed for the crude extracts of Paracamarosporium leucadendri inhibiting Mycobacterium bovis, Klebsiella pneumoniae, and Pseudomonas aeruginosa at 6 µg/mL. Crude extracts of Fusarium sp., showed activity at 9 µg/mL against M. bovis, M. smegmatis and K. pneumonia. In general, the crude extracts showed great activity against Gram-negative and Gram-positive bacteria and novel results for two mycobacteria species M. bovis and M. smegmatis. The results provide evidence of diverse fungal endophytes isolated from Solanum mauritianum, and evidence that fungal endophytes are a good source of bioactive compounds with pharmaceutical potential, particularly against Mycobacterium tuberculosis.

Anticancer activity and metabolite profiling data of Penicillium janthinellum KTMT5.

Fungi are ubiquitous, they proliferate even in environments with toxic pollutants that are otherwise harmful to other eukaryotes. This article presents data of fungi which were isolated from gold mine tailings and identified by DNA sequencing of their inter transcribed spacer regions 1 and 2. Five fungal isolates were identified, among which the crude extract of Penicillium janthinellum KTMT5 was investigated for anticancer activity on A549 (lung carcinoma) and UMG87 (glioblastoma) cell lines. Untargeted metabolite profiling of the crude extract of P. janthinellum KTMT5 was performed using liquid chromatography quadrupole time of flight tandem mass spectrometry (LC-QTOF-MS/MS) and a molecular network generated using the online workflow on the Global Natural Product Social molecular networking (GNPS) website. DNA sequencing showed that all fungal isolates belonged to phylum Ascomycota with the genus Penicillium representing 75% of the fungal isolates. P. janthinellum KTMT5 which was selected for further experiments showed significant anticancer activity against UMG87 cells with a calculated IC50 value of 44.23 µg/mL in the MTS assay, while the real time xCELLigence assay showed dose-dependent anticancer activity at 50 and 100 µg/mL. Metabolite profiling revealed the presence of several known metabolites in the crude extract of P. janthinellum KTMT5 and molecular networking showed the relationships among these metabolites.

Antibacterial and Anticancer Activity and Untargeted Secondary Metabolite Profiling of Crude Bacterial Endophyte Extracts from Crinum macowanii Baker Leaves.

This study isolated and identified endophytic bacteria from the leaves of Crinum macowanii and investigated the potential of the bacterial endophyte extracts as antibacterial and anticancer agents and their subsequent secondary metabolites. Ethyl acetate extracts from the endophytes and the leaves (methanol: dichloromethane (1 : 1)) were used for antibacterial activity against selected pathogenic bacterial strains by using the broth microdilution method. The anticancer activity against the U87MG glioblastoma and A549 lung carcinoma cells was determined by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Bacterial endophytes that were successfully isolated from C. macowanii leaves include Raoultella ornithinolytica, Acinetobacter guillouiae, Pseudomonas sp., Pseudomonas palleroniana, Pseudomonas putida, Bacillus safensis, Enterobacter asburiae, Pseudomonas cichorii, and Arthrobacter pascens. Pseudomonas cichorii exhibited broad antibacterial activity against both Gram-negative and Gram-positive pathogenic bacteria while Arthrobacter pascens displayed the least MIC of 0.0625 mg/mL. Bacillus safensis crude extracts were the only sample that showed notable cell reduction of 50% against A549 lung carcinoma cells at a concentration of 100 µg/mL. Metabolite profiling of Bacillus safensis, Pseudomonas cichorii, and Arthrobacter pascens crude extracts revealed the presence of known antibacterial and/or anticancer agents such as lycorine (1), angustine (2), crinamidine (3), vasicinol (4), and powelline. It can be concluded that the crude bacterial endophyte extracts obtained from C. macowanii leaves can biosynthesize bioactive compounds and can be bioprospected for medical application into antibacterial and anticancer agents.

Cytotoxic activity of crude extracts from Datura stramonium's fungal endophytes against A549 lung carcinoma and UMG87 glioblastoma cell lines and LC-QTOF-MS/MS based metabolite profiling.

BACKGROUND: Endophytic fungi are a proven source of bioactive secondary metabolites that may provide lead compounds for novel drug discovery. In this study, crude extracts from fungal endophytes isolated from Datura stramonium were evaluated for cytotoxic activity on two human cancer cell lines. METHODS: Fungal endophytes were isolated from surface sterilized aerial parts of D. stramonium and identified using molecular, morphological and phylogenetic methods. Ethyl acetate crude extracts from these isolates were evaluated for cytotoxic activity on A549 lung carcinoma and UMG87 glioblastoma cell lines. Metabolite profiling was then performed by liquid chromatography coupled to quadrupole time-of-flight with tandem mass spectrometry (LC-QTOF-MS/MS) for the cytotoxic crude extract. RESULTS: Eleven fungal endophytes were identified from D. stramonium. Significant cytotoxicity was only observed from the crude extract of Alternaria sp. KTDL7 on UMG87 glioblastoma cells (IC50 = 21.49 µg/ml). Metabolite profiling of this crude extract tentatively revealed the presence of the following secondary metabolites: 1,8-dihydroxynaphthalene (1), anserinone B (2), phelligridin B (3), metacytofilin (4), phomopsidin (5) and vermixocin A (6). Compounds 2 and 3 have been shown to be cytotoxic in literature. CONCLUSION: The findings in this study suggest that the crude extract of Alternaria sp. KTDL7 possesses compound(s) cytotoxic to glioblastoma multiforme cells. Future studies to isolate and characterize the cytotoxic compound(s) from this fungus could result in lead development of a fungal-based drug for glioblastoma multiforme treatment.

Dataset on assessment of pollution level of selected trace metals in farming area within the proximity of a gold mine dump, Ekuhurleni, South Africa.

Food security remains an important aspect of human lives and the vital role of soil in the global agricultural and food crops production is obvious. The quality of agricultural products which is being consumed by human through the food chain is dependent on the condition of the soil. Previous gold mining activities resulted in the discharge of tailing materials containing various hazardous trace metals such as manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), chromium (Cr), lead (Pb), and zinc (Zn). 20 representative soil samples were collected from the Gold one Mine tailing dump located in Ekuhurleni, Gauteng Province, South Africa and used in describing the prevalence and concentrations of selected trace metals using inductively coupled plasma optical emission spectrometry (ICP-OES). The concentration of identified trace metals in decreasing order is as follows: Cr > Al > As > Fe > Pb > Co > Ni > Ti > Cd > Zn > Cu. Contamination levels of trace metals in the soils were evaluated using various pollution indices such as contamination factor, degree of contamination, geo-accumulation index, pollution load index and the United States Environmental Protection Agency. These evaluations revealed a high degree and the ultra-high degree of contamination classes of soils. Based on the observed concentrations of trace metals and contamination levels, this study strongly support the call for analysis of the nearby stream and drinking water quality, including the staple crops that are cultivated within the vicinity of the dump site, to ascertain the levels of heavy metals within such crops. Stringent mitigation plans or conversion of the tailing dump into value-added products should be considered.

Concomitant in Situ FTIR and Impedance Measurements To Address the 2-Methylcyclopentanone Vapor-Sensing Mechanism in MnO2-Polymer Nanocomposites.

Polymer nanocomposite-based sensors were prepared using cellulose acetate (CA), carbon nanoparticles (CNPs), and manganese dioxide (MnO2) nanorods to detect and to understand the sensing mechanism of 2-methylcyclopentanone vapor. A sensor with a mass ratio of 1:1.5:3 of MnO2/CNPs/CA as well as MnO2/CA and MnO2/CNP composite and MnO2 sensors were prepared. The sensor with the three sensing materials combined exhibited an enhancement of response for 2-methylcyclopentanone vapor, ascribed to a synergistic effect between MnO2/CNPs/CA. An in situ Fourier-transform infrared (FTIR)-combined online LCR meter setup was used to understand the sensing mechanism of the sensor. The sensing mechanism involved a deep oxidation decomposition of the analyte to CO2. This was confirmed from the in situ FTIR-combined online LCR meter results, where a new distinct CO2 bending mode IR band was recorded. To optimize the performance of the sensor, the composites were prepared by varying the amount of metal oxide added into the composites; sensor A (composition of mass ratio 1:1.5:3), sensor B (composition of mass ratio 2:1.5:3), and sensor C (composition of mass ratio 2.5:1.5:3); their compositions are MnO2/CNPs/CA. The performance of sensor B was higher than that of the other two sensors. The sensors also show relatively good response-recovery time. All fabricated sensors were found to have the sensing ability regenerated after the analyte was removed from the system without losing its sensing and recovery abilities. The structural and morphological features of the samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy.