Papers by Usama Abdelmohsen
Journal of Advanced Pharmacy Research, 2017
Objectives: This study aimed to point the significant rule of metabolomics tools to assess the ch... more Objectives: This study aimed to point the significant rule of metabolomics tools to assess the chemistry of the bioactive metabolites produced by endophytic fungus Aspergillus chevalieri isolated from Lagerostromia tomentosa C. presl. The anticancer of crude extracts, fractions and pure compounds and antimicrobial of pure compounds were investigated as part of this study. Methods: An endophytic fungus (Aspergillus chevalieri) was isolated from the tissues of the stem of Lagerostromia tomentosa C. Presl and identified through molecular biological procedure by DNA isolation, PCR, DNA sequencing and through searching the Gene Bank. Metabolomics profiling and dereplication studies were employed to choose the optimum growth medium and conditions that yield the most significant metabolites. The crude extract of the 30-days rice culture of Aspergillus chevalieri was subjected to bioactivity and metabolomics guided isolation approach. The structure of the isolated compounds was determined on the basis of 1D, 2D NMR and mass spectrometry (HR-ESIMS) analysis. Results: four fractions were further purified to produce five pure compounds, which are Ergosterol (1), Ergosterol peroxide (2), Campesterol (3), Flavoglaucin (4) and 3-O-methyl caffeic acid (5). Multivariate data analysis highlighted the most significant metabolites contributed to the bioactivity. The pure compounds were tested for the anticancer and antimicrobial activity, compound (1) exhibited significant antitrypanosomal activity, while compounds (2, 3, 4 and 5) effectively inhibited the growth of Escherichia coli, Staphylococcus aureus and Candida albicans. Conclusion: A combination of metabolomic-and bioassay-guided approaches gives an access to a shorter and faster route to highlight the active metabolites, which are highly correlated to the bioactivity during the first stage of fractionation.
Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture co... more Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 1–9. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC 50 20 to 30 µg/mL) and antiproliferative activities (IC 50 1.14 to 1.71 µM) agai...
The Journal of antibiotics, Jan 20, 2015
Infectious diseases caused by chlamydia or schistosomes are a major health problem worldwide, and... more Infectious diseases caused by chlamydia or schistosomes are a major health problem worldwide, and particularly so in developing countries. The lack of appropriate vaccines renders the search for potent natural products against these disease-causing agents an urgent endeavor. Sponge-associated actinomycetes represent a rich reservoir for natural products. Among them, members of the genus Streptomyces are capable of synthesizing an impressive array of diverse natural products with a wide variety of biological activities. The naphthacene glycoside SF2446A2 was isolated from the calcium alginate beads culture of Streptomyces sp. strain RV15 that had originally been obtained from the Mediterranean sponge Dysidea tupha. Its structure was identified by spectroscopic analysis and MS and comparison with the literature data. SF2446A2 showed inhibitory activity against Chlamydia trachomatis and was able to inhibit the primary infection in a dose-dependent manner, as well as progeny formation. ...
International journal of systematic and evolutionary microbiology, Jan 17, 2014
A Gram-positive staining, aerobic organism, isolated from the the Red Sea sponge Spheciospongia v... more A Gram-positive staining, aerobic organism, isolated from the the Red Sea sponge Spheciospongia vagabunda was investigated for its taxonomic position. Based on 16S rRNA gene sequence analysis strain EG49T was most closely related to Actinokineospora cibodasensis and Actinokineospora baliensis (both 97.3%) and Actinokineospora diospyrosas and Actinokineospora auranticolor (both 97.0%). The 16S rRNA gene sequence similarity to all other Actinokineospora species was < 97.0 %. The quinone system of strain EG49T contains the menaqinone MK-9(H4), (47%), MK-9(H6), (27%) and MK-9(H2), (15%) in major amounts. Minor amounts of MK-7(H4), (2%), MK-9(H0), (1%), MK-9(H8) (3%) and MK-10(H4) (3%) were detected as well in addition to MK-8(H4), MK-8(H6), MK-10(H2) and MK-10(H6) (all <1%). The diagnostic diaminoacid of the peptidoglycan is meso-diaminopimelic acid. In the polar lipid profile, diphosphatidylglycerol, phosphatidylethanolamine, and hydroxyl-phosphatidylethanolamine are predominant....
Tetrahedron Letters, 2012
... Streptomyces strain RV15 Usama Ramadan Abdelmohsena,†, Guoliang Zhangb,†, Allan Philippeb... more ... Streptomyces strain RV15 Usama Ramadan Abdelmohsena,†, Guoliang Zhangb,†, Allan Philippeb, Werner Schmitzc, Sheila Marie Pimentel-Elardoa, Barbara Hertlein-Amslingerb, Ute ... 7. Pimentel-Elardo, SM; Kozytska, S.; Bugni, TS; Ireland, CM; Moll, H.; Hentschel, U. Mar. ...
Plant Cell, Tissue and Organ Culture (PCTOC), 2010
The aim of this study was to evaluate the potential of plant suspension cultures for the producti... more The aim of this study was to evaluate the potential of plant suspension cultures for the production of antimicrobial activities. The extracellular, intracellular and cell wall bound fractions of 16 heterotrophic, photoautotrophic and photomixotrophic plant cell suspension cultures each treated with nine different elicitors were tested for the elicitor dependent production of antimicrobial activities. Distinctly different patterns of bioactivities directed against a panel of human isolates including Grampositive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria as well as fungi (Candida maltosa) were identified for all except the two autotrophic cell cultures. The intracellular fractions of elicited cell cultures were more active than extracellular fractions while cell wall bound fractions showed almost no activities. The intracellular fraction of heterotrophic Lavendula angustifolia cells elicited with a preparation of Pseudomonas syringae was the most active fraction against Candida maltosa. The intracellular fraction of photomixotrophic Arabidopsis thaliana cells elicited with salicylic acid was active against all test isolates. An antimicrobial protein could be identified and partially purified from this culture. Our findings suggest that elicited plant cell cultures may present a new promising alternative source of antimicrobial proteins.
International Journal of Systematic and Evolutionary Microbiology, 2013
A Gram-stain-positive, non-spore-forming bacterium (strain RV113T) was isolated from the marine s... more A Gram-stain-positive, non-spore-forming bacterium (strain RV113T) was isolated from the marine sponge Aplysina aerophoba. 16S rRNA gene sequence analysis showed that strain RV113T belongs to the genus Rubrobacter , and is related most closely to Rubrobacter bracarensis VF70612_S1T (96.9 % similarity) and more distantly related (<93 %) to all other species of the genus Rubrobacter . The peptidoglycan diamino acid was lysine. Strain RV113T exhibited a quinone system with menaquinone MK-8 as the predominant compound. The polar lipid profile of strain RV113T consisted of the major compounds phosphatidylglycerol and two unidentified phosphoglycolipids. The major fatty acid was anteiso-C17 : 0ω9c. These chemotaxonomic traits are in agreement with those of other species of the genus Rubrobacter . The results of physiological and biochemical tests allowed the clear phenotypic differentiation of strain RV113T from all recognized Rubrobacter species. Strain RV113T is thus considered to re...
Frontiers in microbiology, 2018
Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged ... more Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 µg/ml) and biofilm formation (sub-MIC range: 1.95-<31.25 µg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its nontoxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs.
Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture co... more Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 1–9. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC 50 20 to 30 µg/mL) and antiproliferative activities (IC 50 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a pharmacophore model of the active compounds was generated to build up a structure-activity relationship.
Phytochemical analysis : PCA, Jan 19, 2018
Marine sponge-associated actinomycetes are potent sources of bioactive natural products of pharma... more Marine sponge-associated actinomycetes are potent sources of bioactive natural products of pharmaceutical significance. They also contributed to the discovery of several clinically relevant antimicrobials. To apply the non-targeted metabolomics approach in chemical profiling of the sponge-derived bacterium Rhodococcus sp. UA13, formerly recovered from the Red Sea sponge Callyspongia aff. Implexa, along with testing for the anti-infective potential of its different fractions. Metabolomic analysis of the crude extract was carried out using liquid chromatography with high resolution electrospray ionisation mass spectrometry (LC-HR-ESI-MS) for dereplication purposes. Besides, the three major fractions (ethyl acetate, methanol, and n-butanol) obtained by chromatographic fractionation of the crude extract were evaluated for their anti-infective properties. A variety of metabolites, mostly peptides, were characterised herein for the first time from the genus Rhodococcus. Among the tested s...
Marine drugs, Jan 29, 2018
Actinomycetes are a relevant source of novel bioactive compounds. One of the pharmaceutically and... more Actinomycetes are a relevant source of novel bioactive compounds. One of the pharmaceutically and biotechnologically important genera that attract natural products research is the genus mainly for its ability to produce a wide variety of secondary metabolites accounting for its wide range of biological activities. This review covers the literature from January 2015 until February 2018 making a complete survey of all the compounds that were isolated from the genus their biological activities, and natural sources, whenever applicable.
Marine drugs, Jan 6, 2017
A new cyclic dipeptide, petrocidin A (), along with three known compounds-2,3-dihydroxybenzoic ac... more A new cyclic dipeptide, petrocidin A (), along with three known compounds-2,3-dihydroxybenzoic acid (), 2,3-dihydroxybenzamide (), and maltol ()-were isolated from the solid culture ofsp. SBT348. The strainsp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey's reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A () and 2,3-dihydroxybenzamide () exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for ...
Medicinal Chemistry Research, 2017
A new azepino-diindole alkaloid; rhodozepinone (1), along with five known compounds, including 2-... more A new azepino-diindole alkaloid; rhodozepinone (1), along with five known compounds, including 2-amino-3-[2(1H)-quinolinon-4-yl]propionic acid (2), 3-hydroxy-2methyl-4H-pyran-4-one (maltol) (3), phenyl acetic acid methyl ester (4), indole-3-acetic acid (5), and 2-amino-3-(1Hindol-3-yl) propanoic acid (tryptophan) (6) were isolated and identified from the broth culture of Rhodococcus sp. UA13, which had been previously recovered from the Red Sea sponge Callyspongia aff. Implexa. The structures of compounds (1-6) were determined by spectroscopic analyses, including 1D and 2D NMR experiments in combination with HR-ESI-MS, as well as comparison with the literature. All the characterized metabolites were firstly reported herein from this marine sponge-associated actinomycete, and among them, (3), (4), and (6) were characterized for the first time from the genus Rhodococcus, whereas this is the first report for isolation of compound (2) from a natural source. Moreover, both the antimicrobial and antitrypanosomal properties of the isolated metabolites (1-6) were evaluated, and only rhodozepinone (1) exhibited significant antibacterial and antitrypanosomal activities against Staphylococcus aureus NCTC 8325 (IC 50 = 8.9 µg/ml) and Trypanosoma brucei brucei TC221 [IC 50 = 16.3 (48 h) and 11.8 (72 h) µg/ml], respectively. These results totally reflected the potential of sponge-derived actinomycetes as a rich source of new natural products with interesting bioactivities, as well as their promising future contribution to drug discovery.
Frontiers in Microbiology, 2017
Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosoc... more Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and nonproteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation
International journal of systematic and evolutionary microbiology, 2016
A Gram-stain-positive, non-endospore-forming actinobacterium (ARP1T) was isolated from the phyllo... more A Gram-stain-positive, non-endospore-forming actinobacterium (ARP1T) was isolated from the phyllosphere of Arabidopsis thaliana. On the basis of 16S rRNA gene sequence phylogeny strain ARP1T was placed into the genus Williamsia and the closest related species were Williamsia phyllosphaerae (98.5 % 16S rRNA gene sequence similarity), Williamsia deligens (98.5 %), Williamsia maris (98.3 %) and Williamsia serinedens (98.2 %). Genome-based comparison indicated a clear distinction to the type strains of those species with pairwise average nucleotide identities (ANI) between 76.4-78.4 %. The quinone system of strain ARP1T consisted predominantly of menaquinones MK-9(H2), MK-7(H2) and MK-8(H2), and the polar lipid profile contained the major compound diphosphatidylglycerol, and moderate amounts of phosphatidylethanolamine, phosphatidylglycerol and numerous unidentified lipids. Mycolic acids were present. These chemotaxonomic traits and the major fatty acids, which were C16 : 1ω7c, C16 : 0,...
Journal of natural products, Jan 28, 2017
The metabolite profiles of three sponge-derived actinomycetes, namely, Micromonospora sp. RV43, R... more The metabolite profiles of three sponge-derived actinomycetes, namely, Micromonospora sp. RV43, Rhodococcus sp. RV157, and Actinokineospora sp. EG49 were investigated after elicitation with N-acetyl-d-glucosamine. (1)H NMR fingerprint methodology was utilized to study the differences in the metabolic profiles of the bacterial extracts before and after elicitation. Our study found that the addition of N-acetyl-d-glucosamine modified the secondary metabolite profiles of the three investigated actinomycete isolates. N-Acetyl-d-glucosamine induced the production of 3-formylindole (11) and guaymasol (12) in Micromonospora sp. RV43, the siderophore bacillibactin 16, and surfactin antibiotic 17 in Rhodococcus sp. RV157 and increased the production of minor metabolites actinosporins E-H (21-24) in Actinokineospora sp. EG49. These results highlight the use of NMR fingerprinting to detect changes in metabolism following addition of N-acetyl-d-glucosamine. N-Acetyl-d-glucosamine was shown to h...
Environmental microbiology, Jan 28, 2017
Comparative genomics is providing new opportunities to address the diversity and distributions of... more Comparative genomics is providing new opportunities to address the diversity and distributions of genes encoding the biosynthesis of specialized metabolites. An analysis of 119 genome sequences representing three closely related species of the marine actinomycete genus Salinispora reveals extraordinary biosynthetic diversity in the form of 176 distinct biosynthetic gene clusters (BGCs) of which only 24 have been linked to their products. Remarkably, more than half of the BGCs were observed in only one or two strains, suggesting they were acquired relatively recently in the evolutionary history of the genus. These acquired gene clusters are concentrated in specific genomic islands, which represent hot spots for BGC acquisition. While most BGCs are stable in terms of their chromosomal position, others migrated to different locations or were exchanged with unrelated gene clusters suggesting a plug and play type model of evolution that provides a mechanism to test the relative fitness e...
Natural product research, Jan 13, 2017
The production of shiga toxin (Stx) is a critical step in the establishment and progress of enter... more The production of shiga toxin (Stx) is a critical step in the establishment and progress of enterohemorrhagic Escherichia coli (EHEC) infections. The possible release of Stx from dead and dying bacteria, and the risk of resistance development have restricted the usage of antibiotics against EHEC. The chlorinated quaternary ammonium compound, strepthonium A, was isolated from the culture of Streptomyces sp. SBT345 that was cultivated from the Mediterranean sponge Agelas oroides. The structure was elucidated and confirmed by spectroscopic analyses including 1D and 2D NMR, ESI-HRMS, as well as ESI-HRMS(2). Strepthonium A follows Lipinski's rule of five with respect to its molecular weight, CLogP values and the number of hydrogen acceptors and donors. Verotoxin ELISA assay demonstrated that Strepthonium A reduced the Stx production in EHEC strain EDL933 at 80 μM concentration without growth inhibition. This study demonstrates the potential of strepthonium A in restraining the produc...
Molecules (Basel, Switzerland), Jan 11, 2017
Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacolog... more Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.
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Papers by Usama Abdelmohsen