Chemical Profiling and Biological Screening of Some River Nile Derived-Microorganisms

AimsChemical and biological studies of the River Nile derived-microorganisms are limited. Hence, this work was carried out to screen the River Nile habitat. Identification of the isolated organisms, chemical profiling of their ethyl acetate extracts as well as screening of their antimicrobial, antileishmanial, antitrypanosomal, and antimalarial activities were investigated.MethodsIdentification of the microbial isolates were carried out using bacterial 16S rRNA and fungal 18S rRNA gene sequencing. Chemical profiling of the EtOAc extracts using LC-HRESIMS spectroscopy was carried out. The in vitro antimicrobial screening using the modified version of the CLSI method, antileishmanial and antitrypanosomal activities were screened using Leishmania donovani promastigote assay, L. donovani axenic amastigote assay, Trypanosoma brucei trypamastigotes assay and THP1 toxicity assay. The in vitro antimalarial activities against D6 (chloroquine sensitive) and W2 (chloroquine-resistant) strains of Plasmodium falciparum were evaluated.ResultsSeven isolated microorganisms were identified as Streptomyces indiaensis, Bacillus safensis, B. anthracis, Bacillus sp., and Aspergillus awamori. Chemical investigation of different extracts showed several bioactive compounds, identified as; nigragillin, 5-caboxybenzofuran and dyramide B from A. awamori and actinopolysporin B from S. indiaensis. On the other hand many nitrogenous compounds with high molecular weights showed no hits that may correspond to new long chain and/or cyclic peptides. The EtOAc extract of B. safensis fermentation broth showed the highest activity against P. falciparum D6 and P. falciparum W2 (IC50 = 25.94 and 27.28 μg/mL, respectively), while two isolates S. indiaensis and Bacillus sp. RN-011 extracts showed the highest antitrypanosomal activity (IC50 = 0.8 and 0.96 μg/mL).ConclusionThe River Nile could be a new source for production of promising bioactive leading compound where antimicrobial and antiparasitic activities may be correlated

Flavonoid-coated gold nanoparticles as efficient antibiotics against gram-negative bacteria—evidence from in silico-supported in vitro studies

Flavonoids are a class of bioactive plant-derived natural products that exhibit a broad range of biological activities, including antibacterial ones. Their inhibitory activity toward Gram-positive bacterial was found to be superior to that against Gram-negative ones. In the present study, a number of flavonoid-coated gold nanoparticles (GNPs) were designed to enhance the antibacterial effects of chrysin, kaempferol, and quercetin against a number of Gram-negative bacteria. The prepared GNPs were able to conjugate to these three flavonoids with conjugation efficiency ranging from 41% to 80%. Additionally, they were able to exert an enhanced antibacterial activity in comparison with the free flavonoids and the unconjugated GNPs. Quercetin-coated GNPs were the most active nano-conjugates and were able to penetrate the cell wall of E. coli. A number of in silico experiments were carried out to explain the conjugation efficiency and the antibacterial mechanisms of these flavonoids as follows: (i) these flavonoids can efficiently bind to the glutathione linker on the surface of GNPs via H-bonding; (ii) these flavonoids, particularly quercetin, were able to increase the bacterial membrane rigidity, and hence decrease its functionality; (iii) these flavonoids can inhibit E. coli’s DNA gyrase (Gyr-B) with IC(50) values ranging from 0.9 to 3.9 µM. In conclusion, these bioactive flavonoid-based GNPs are considered to be very promising antibiotic candidates for further development and evaluation

Prevalence of Bacteria in Primary Schools

Pathogenic microorganisms are serious threats in schools, where contact with many microorganisms occur frequently throughout the school day. Classrooms are considered an optimal place for contact between microorganisms and young children. The aim of the current study was to study the prevalence of bacteria isolated in samples from different sites in primary schools and to show whether schools are sanitized and clean for children or it is just the core reason for their illness. The study was done in a highly standard private school and a public school in order to study the effect of variance in the social classes on the cleanliness of the schools. Different colonies were separated and identified by staining techniques and biochemical tests. Thirteen different types of bacteria with different amounts were isolated from 176 samples collected from different surfaces. It was found that the number of bacteria in public school is higher than that of the private school. The distribution of bacterial strains isolated from the two schools averaged 37.1% for Staphylococcus sp. followed by 11.3% for Enterobacter sp. and then 7.3%, 7.1% and 6.3% for Yersinia sp. Streptococcus sp. and Micrococcus sp. respectively. Other strains ranged between 5.9% to 1.5%. Bacterial isolates were tested for their susceptibility by well diffusion test against three commercial disinfectants commonly used for surface and hand cleaning in schools, namely; Clorox, Renol and Dettol. The highest percentage of resistance was seen against Renol (50%) followed by Dettol (38%) and was identified to be Escherichia coli, while least resistance occurring among all isolates was noticed against Clorox (18%). Children in private and public schools are at high risk of catching serious bacterial infections and they are surrounded by a cram of microorganisms. The current research shows that new ways must be developed to improve our schools’ hygiene to make it a healthier and safer place to learn in

The Chemical Profiling, Docking Study, and Antimicrobial and Antibiofilm Activities of the Endophytic fungi Aspergillus sp. AP5

Growing data suggest that Aspergillus niger, an endophytic fungus, is a rich source of natural compounds with a wide range of biological properties. This study aimed to examine the antimicrobial and antibiofilm capabilities of the Phragmites australis-derived endophyte against a set of pathogenic bacteria and fungi. The endophytic fungus Aspergillus sp. AP5 was isolated from the leaves of P. australis. The chemical profile of the fungal crude extract was identified by spectroscopic analysis using LC-HRESIMS. The fungal-derived extract was evaluated for its antimicrobial activity towards a set of pathogenic bacterial and fungal strains including Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella sp., Candida albicans, and Aspergillus niger. Moreover, antibiofilm activity toward four resistant biofilm-forming bacteria was also evaluated. Additionally, a neural-networking pharmacophore-based visual screening predicted the most probable bioactive compounds in the obtained extract. The AP5-EtOAc extract was found to have potent antibacterial activities against S. aureus, E. coli, and Klebsiella sp., while it exhibited low antibacterial activity toward P. Vulgaris and P. aeruginosa and displayed anticandidal activity. The AP5-EtOAc extract had significant antibiofilm activity in S. aureus, followed by P. aeruginosa. The active metabolites’ antifungal and/or antibacterial activities may be due to targeting the fungal CYP 51 and/or the bacterial Gyr-B

Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling

In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out of them, Micromonospora sp. UR17 was putatively characterized as a new species. In order to explore the chemical diversity of these actinobacteria as far as possible, they were subjected to a series of fermentation experiments under altering conditions, that is, solid and liquid fermentation along with co-fermentation with a mycolic acid-containing strain, namely Nocardia sp. UR23. Each treatment was found to affect these actinomycetes differently in terms of biological activity (i.e., antitrypanosomal activity) and chemical profiles evidenced by LC-HRES-MS-based metabolomics and multivariate analysis. Thereafter, orthogonal projections to latent structures discriminant analysis (OPLS-DA) suggested a number of metabolites to be associated with the antitrypanosomal activity of the active extracts. The subsequent in silico screenings (neural networking-based and docking-based) further supported the OPLS-DA results and prioritized desferrioxamine B (3), bafilomycin D (10), and bafilomycin A1 (11) as possible antitrypanosomal agents. Our approach in this study can be applied as a primary step in the exploration of bioactive natural products, particularly those from actinomycetes

Cnicin as an anti-SARS-CoV-2:an integrated in silico and in vitro approach for the rapid identification of potential COVID-19 therapeutics

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract’s antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein–protein and protein–compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic

Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp.

Malaria is a persistent illness with a great public health concern. To combat this fatal disease, developing effective antimalarial medications has become a necessity. In the present study, we described the actinomycetes associated with the Red Sea soft coral Nephthea sp. and isolated a strain that was sub-cultured in three different media (M1, ISP2, and OLIGO). Actinomycete isolate’s phylogenetic analysis of the 16S rRNA gene revealed that it belongs to the genus Rhodococcus. In vitro screening of the antimalarial activity for three extracts against Plasmodium falciparum was carried out. Non-targeted metabolomics for the chemical characterization of the isolated actinomycete species UA111 derived extracts were employed using high-resolution liquid chromatography–mass spectrometry (LC-HR-MS) for dereplication purposes. Additionally, statistical analysis of the vast LC-MS data was performed using MetaboAnalyst 5.0. Finally, an in silico analysis was conducted to investigate the potential chemical compounds that could be the source of the antimalarial potential. The results revealed that ISP2 media extract is the most effective against Plasmodium falciparum, according to antimalarial screening (IC50 8.5 µg/mL), in contrast, OLIGO media extract was inactive. LC-HRMS-based metabolomics identified a range of metabolites, mainly alkaloids, from the genus Rhodococcus. On the other hand, multivariate analysis showed chemical diversity between the analyzed samples, with ISP2 extract being optimal. The docking analysis was able to anticipate the various patterns of interaction of the annotated compounds with three malarial protein targets (P. falciparum kinase, P. falciparum cytochrome bc1 complex, and P. falciparum lysyl-tRNA synthetase). Among all of the test compounds, perlolyrine (11) and 3097-B2 (12) displayed the best docking profiles. In conclusion, this work demonstrated the value of the established method for the metabolic profiling of marine actinomycetes using the data from liquid chromatography–mass spectrometry (LC-MS), which helps to streamline the difficult isolation stages required for their chemical characterization. In addition, the antimalarial efficacy of this strain has intriguing implications for future pharmaceutical development