Publications by authors named "Ahmed O El-Gendy"

22 Publications

  • Page 1 of 1

The effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus: An in vitro study.

J Photochem Photobiol B 2021 Aug 4;221:112240. Epub 2021 Jun 4.

Laser Institute for Research and Applications LIRA, Beni-Suef University, Beni-Suef 62511, Egypt. Electronic address:

We investigated the effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus. In order to improve laser-based antimicrobial therapy and develop a clinically viable modality, various laser parameters such as laser light wavelength, laser power, exposure time, and energy density were studied. The INSPIRE HF100 laser system (Spectra Physics) provided the femtosecond laser light, which was pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP (Spectra Physics). The survival of the bacterial cells was monitored after irradiation by determination of growth rate using optical density, which is a rapid, simple, and reliable method. The growth rate of laser-exposed cultures was compared to control cultures. Fifteen minutes of exposure to femtosecond laser radiation with a wavelength of 390 nm and 400 nm at an average power of 50 mW was enough to significantly reduce bacterial viability, with a lag in the growth phase of 5 h longer than the control culture (P < 0.0001 by ANOVA and Tukey test).
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http://dx.doi.org/10.1016/j.jphotobiol.2021.112240DOI Listing
August 2021

Antimicrobial Activity of Cationic Poly(3-hexylthiophene) Nanoparticles Coupled with Dual Fluorescent and Electrochemical Sensing: Theragnostic Prospect.

Sensors (Basel) 2021 Mar 2;21(5). Epub 2021 Mar 2.

Université Paris-Saclay, CNRS, Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), ECBB, 91400 Orsay, France.

Designing therapeutic and sensor materials to diagnose and eliminate bacterial infections remains a significant challenge for active theragnostic nanoprobes. In the present work, fluorescent/electroactive poly(3-hexylthiophene) P3HT nanoparticles (NPs) stabilized with quaternary ammonium salts using cetyltrimethylammonium bromide (CTAB), (CTAB-P3HT NPs) were prepared using a simple mini-emulsion method. The morphology, spectroscopic properties and electronic properties of CTAB-P3HT NPs were characterized by DLS, zeta potential, SEM, TEM, UV-vis spectrophotometry, fluorescence spectroscopy and electrochemical impedance spectroscopy (EIS). In an aqueous solution, CTAB-P3HT NPs were revealed to be uniformly sized, highly fluorescent and present a highly positively charged NP surface with good electroactivity. Dual detection was demonstrated as the binding of the bacteria to NPs could be observed by fluorescence quenching as well as by the changes in EIS. Binding of to CTAB-P3HT NPs was demonstrated and LODs of 5 CFU/mL and 250 CFU/mL were obtained by relying on the fluorescence spectroscopy and EIS, respectively. The antimicrobial activity of CTAB-P3HT NPs on bacteria and fungi was also studied under dark and nutritive conditions. An MIC and an MBC of 2.5 µg/mL were obtained with and with , and of 0.312 µg/mL with . Additionally a good biocompatibility toward normal human cells (WI38) was observed, which opens the way to their possible use as a therapeutic agent.
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http://dx.doi.org/10.3390/s21051715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958628PMC
March 2021

Purification and characterization of bacteriocins-like inhibitory substances from food isolated Enterococcus faecalis OS13 with activity against nosocomial enterococci.

Sci Rep 2021 Feb 15;11(1):3795. Epub 2021 Feb 15.

Department of Microbiology and Immunology, Nahda University, Beni Suef, Egypt.

Nosocomial infections caused by enterococci are an ongoing global threat. Thus, finding therapeutic agents for the treatment of such infections are crucial. Some Enterococcus faecalis strains are able to produce antimicrobial peptides called bacteriocins. We analyzed 65 E. faecalis isolates from 43 food samples and 22 clinical samples in Egypt for 17 common bacteriocin-encoding genes of Enterococcus spp. These genes were absent in 11 isolates that showed antimicrobial activity putatively due to bacteriocins (three from food, including isolate OS13, and eight from clinical isolates). The food-isolated E. faecalis OS13 produced bacteriocin-like inhibitory substances (BLIS) named enterocin OS13, which comprised two peptides (enterocin OS13α OS13β) that inhibited the growth of antibiotic-resistant nosocomial E. faecalis and E. faecium isolates. The molecular weights of enterocin OS13α and OS13β were determined as 8079 Da and 7859 Da, respectively, and both were heat-labile. Enterocin OS13α was sensitive to proteinase K, while enterocin OS13β was resistant. Characterization of E. faecalis OS13 isolate revealed that it belonged to sequence type 116. It was non-hemolytic, bile salt hydrolase-negative, gelatinase-positive, and sensitive to ampicillin, penicillin, vancomycin, erythromycin, kanamycin, and gentamicin. In conclusion, BLIS as enterocin OS13α and OS13β represent antimicrobial agents with activities against antibiotic-resistant enterococcal isolates.
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http://dx.doi.org/10.1038/s41598-021-83357-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884432PMC
February 2021

A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes.

Sci Rep 2021 Feb 2;11(1):2770. Epub 2021 Feb 2.

Bioproducts Research Chair, Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.

Fungal endophytes are a major source of anti-infective agents and other medically relevant compounds. However, their classical blinded-chemical investigation is a challenging process due to their highly complex chemical makeup. Thus, utilizing cheminformatics tools such as metabolomics and computer-aided modelling is of great help deal with such complexity and select the most probable bioactive candidates. In the present study, we have explored the fungal endophytes associated with the well-known antimalarial medicinal plant Artemisia annua for their production of further antimalarial agents. Based on the preliminary antimalarial screening of these endophytes and using LC-HRMS-based metabolomics and multivariate analyses, we suggested different potentially active metabolites (compounds 1-8). Further in silico investigation using the neural-network-based prediction software PASS led to the selection of a group of quinone derivatives (compounds 1-5) as the most possible active hits. Subsequent in vitro validation revealed emodin (1) and physcion (2) to be potent antimalarial candidates with IC values of 0.9 and 1.9 µM, respectively. Our approach in the present investigation therefore can be applied as a preliminary evaluation step in the natural products drug discovery, which in turn can facilitate the isolation of selected metabolites notably the biologically active ones.
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http://dx.doi.org/10.1038/s41598-021-82201-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854678PMC
February 2021

Metabolomic profiling and antioxidant potential of three fungal endophytes derived from and .

Nat Prod Res 2020 Oct 12:1-5. Epub 2020 Oct 12.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt.

In this work, three fungal endophytes identified as (AFL, AFSt and AFR), were studied for their antioxidant potential. LC-MS-based metabolomics, followed by multivariate statistical analysis were then applied to comprehensively profile their extracts. The three fungal endophytes revealed interesting antioxidant potential, in particular, the strain isolated from the leaves (AFL), which was rich in different types of phenolic metabolites. Additionally, all fungal-derived ethyl acetate extracts showed potent inhibition against the prooxidant xanthine oxidase. Multivariate analysis (PCA and PLS-DA) demonstrated a unique chemical fingerprint for each strain, where phenolics, coumarins, and polyketides were the discriminative metabolites of the three fungal strains. The present findings highlighted the power of metabolomics in the chemotaxonomical classification of closely related strains. It also asserted the role of fungal endophytes in the management of oxidative stress, particularly when they are utilized in the production of fermented food products.
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http://dx.doi.org/10.1080/14786419.2020.1831495DOI Listing
October 2020

Anti-Proliferative and Anti-Biofilm Potentials of Bacteriocins Produced by Non-Pathogenic Enterococcus sp.

Probiotics Antimicrob Proteins 2021 Apr 3;13(2):571-585. Epub 2020 Oct 3.

Microbiology and Immunology Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.

The incidence of cancer is increasing worldwide; likewise, the emergence of antibiotic-resistant biofilm-forming pathogens has led to a tremendous increase in morbidity and mortality. This study aimed to evaluate the probiotic properties of bacteriocin-producing Enterococcus sp. with a focus on their anti-biofilm and anticancer activities. Three of 79 Enterococcus isolates (FM43, FM65, FM50) were identified as producers of broad-spectrum bioactive molecules and were molecularly characterized as Enterococcus faecium by 16S rRNA sequencing. Phenotypic and genotypic screening for potential virulence factors revealed no factors known to promote pathogenicity. Treatment with proteinase K resulted in diminished antimicrobial activity; PCR-based screening for bacteriocin genes suggested the presence of both entA and entB genes that encode enterocins A and B, respectively. Maximum antimicrobial activity was detected during the early stationary phase, while activity disappeared after 24 h in culture. Bacteriocins from these isolates were stable at high temperatures and over a wide range of pH. Interestingly, crude supernatants of Ent. faecium FM43 and Ent. faecium FM50 resulted in significant destruction (80% and 48%, respectively; P < 0.05) of Streptococcus mutans ATCC 25175-associated preformed biofilms. Moreover, in vitro cytotoxicity assays revealed that extracts from Ent. faecium isolates FM43, FM65, and FM50 inhibited Caco-2 cell proliferation by 76.9%, 70%, and 85.3%, respectively. Taken together, the multifunctional capabilities of the microbial-derived proteins identified in our study suggest potentially important roles as alternative treatments for biofilm-associated infections and cancer.
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http://dx.doi.org/10.1007/s12602-020-09711-1DOI Listing
April 2021

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.

Antibiotics (Basel) 2020 Sep 22;9(9). Epub 2020 Sep 22.

Bioproducts Research Chair, Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera , , and ; out of them, 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 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 (), bafilomycin D (), and bafilomycin A1 () 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.
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http://dx.doi.org/10.3390/antibiotics9090629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558093PMC
September 2020

Public awareness in Egypt about COVID-19 spread in the early phase of the pandemic.

Patient Educ Couns 2020 Sep 5. Epub 2020 Sep 5.

Clinical Pharmacy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address:

Objective: This study aimed to evaluate public awareness in Egypt related to the coronavirus.

Methods: An online structured survey was conducted during March and April 2020 to assess coronavirus knowledge. The questionnaire was divided into 6 parts consisting of 39 questions for a total possible score of 0 to 39; to assess the participants' general knowledge [10 items]; symptoms knowledge [2 items]; transmission knowledge [6 items]; preventive knowledge [4 items]; treatment knowledge [6 items], and public knowledge of governmental and international efforts [10 items].

Results: A total of 726 participants participated, 97.5% of them knew the main clinical symptoms of coronaviruses. 99% believed that following the etiquette of coughing, sneezing, or wearing a medical mask is important to reduce infection transmission. 80.5% of the participants believed that there is no effective treatment or vaccine available for the coronavirus. The important role of the international organizations to overcome the coronavirus was known by (92.3%). 65.2% believed that the Ministry of Health provided reliable data on the number of infections or death. 27.9% of the participants consider coronavirus infection as a stigma. The average score of this survey was 31.75/39 (81.4%) regarding the knowledge about the disease.

Conclusion: Overall, the study participants' had good knowledge of coronavirus and the international efforts to confront the coronavirus.

Practice Implications: Further study is required to evaluate the effect of such good knowledge on decreasing the infection rate.
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http://dx.doi.org/10.1016/j.pec.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833955PMC
September 2020

Dispersible Conjugated Polymer Nanoparticles as Biointerface Materials for Label-Free Bacteria Detection.

ACS Appl Mater Interfaces 2020 Sep 26;12(36):39979-39990. Epub 2020 Aug 26.

Université Paris-Saclay, CNRS, Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), ECBB, Bât 420, 2 Rue du Doyen Georges Poitou, 91400 Orsay, France.

Fast and efficient identification of bacterial pathogens in water and biological fluids is an important issue in medical, food safety, and public health concerns that requires low-cost and efficient sensing strategies. Impedimetric sensors are promising tools for monitoring bacteria detection because of their reliability and ease-of-use. We herein report a study on new biointerface-based amphiphilic poly(3-hexylthiophene)--poly(3-triethylene-glycol-thiophene), P3HT--P3TEGT, for label-free impedimetric detection of (). This biointerface is fabricated by the self-assembly of P3HT--P3TEGT into core-shell nanoparticles, which was further decorated with mannose, leading to an easy-to-use solution-processable nanoparticle material for biosensing. The hydrophilic block P3TEGT promotes antifouling and prevents nonspecific interactions, while improving the ionic and electronic transport properties, thus enhancing the electrochemical-sensing capability in aqueous solution. Self-assembly and micelle formation of P3HT--P3TEGT were analyzed by 2D-NMR, Fourier transform infrared, dynamic light scattering, contact angle, and microscopy characterizations. Detection of was characterized and evaluated using electrochemical impedance spectroscopy and optical and scanning electron microscopy techniques. The sensing layer based on the mannose-functionalized P3HT--P3TEGT nanoparticles demonstrates targeting ability toward pili protein with a detection range from 10 to 10 cfu/mL, and its selectivity was studied with Gram(+) bacteria. Application to real samples was performed by detection of bacteria in tap and the Nile water. The approach developed here shows that water/alcohol-processable-functionalized conjugated polymer nanoparticles are suitable for use as electrode materials, which have potential application in fabrication of a low-cost, label-free impedimetric biosensor for the detection of bacteria in water.
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http://dx.doi.org/10.1021/acsami.0c08305DOI Listing
September 2020

The bactericidal efficacy of femtosecond laser-based therapy on the most common infectious bacterial pathogens in chronic wounds: an in vitro study.

Lasers Med Sci 2021 Apr 28;36(3):641-647. Epub 2020 Jul 28.

Laser Institute for Research and Applications LIRA, Beni-Suef University, Beni-Suef, 62511, Egypt.

We investigated the influence of femtosecond laser irradiation on the growth of the two most common infectious bacterial pathogens in wounds; Staphylococcus aureus and Pseudomonas aeruginosa as an attempt to validate optimum parameters for a laser-based bactericidal modality to be used clinically. Bacterial cultures were exposed to femtosecond laser irradiation at different wavelengths, exposure times, and laser powers. The source of femtosecond laser was INSPIRE HF100 laser system, Spectra-Physics, which is pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP, Spectra-Physics. After irradiation, bacterial cells' survival was monitored by observing the clear zones of inhibition in cultured agar plates. Results for all strains indicated that the exposure to femtosecond laser irradiation with a wavelength ranging from ultraviolet (λ > 350 nm) to blue laser light (λ < 480 nm), for a period above 20 min and with a power density of ≈ 0.063 W/cm, was enough to inhibit both bacterial pathogens with the results maintained for 1 week following irradiation.
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http://dx.doi.org/10.1007/s10103-020-03104-0DOI Listing
April 2021

The biosurfactants iturin, lichenysin and surfactin, from vaginally isolated lactobacilli, prevent biofilm formation by pathogenic Candida.

FEMS Microbiol Lett 2020 08;367(15)

Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Lactic acid bacteria (LAB), particularly lactobacilli, are major components of the vaginal microbiota. Lactobacilli are facultative anaerobes forming a critical line of defense against pathogenic microorganisms, including those forming biofilms, such as Candida spp. This study aimed to investigate the anti-adhesion capabilities of vaginal Lactobacillus isolates against biofilms formed by pathogenic Candida species. When the extracellular biosurfactant activities of culture supernatants from 120 Lactobacillus isolates were evaluated by the oil-spreading method, clear spreading zones were recognized. Biofilm formation was quantified by the crystal violet plate assay, and different isolates exhibited anti-adhesion activity that ranged from 65.6to 74.4% inhibition against Candida spp. biofilms. Liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HRESIMS) identified biosurfactants, extracted from three representative Lactobacillus isolates, as surfactin, iturin and lichenysin. Finally, the distribution of representative genes from six different biosynthetic clusters, related to the production of different biosurfactants, was investigated by the polymerase chain reaction. In conclusion, surfactin, iturin and lichenysin were identified for the first time in vaginal Lactobacillus spp. These biosurfactants, which showed strong anti-adherence activity may be used as promising antibiofilm agents in equipment care to prevent vaginal infections by pathogenic Candida spp. with the prospect of reducing nosocomial infections.
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http://dx.doi.org/10.1093/femsle/fnaa126DOI Listing
August 2020

Microbial Natural Products as Potential Inhibitors of SARS-CoV-2 Main Protease (M).

Microorganisms 2020 Jun 29;8(7). Epub 2020 Jun 29.

School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.

The main protease (M) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski's rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme's conformers. Final MDS experiments were performed on the ligand-protein complexes (compounds Table S1) to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds () was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the M structural flexibility during interactions with the possible inhibitors and sheds light on the structure-based design of anti-coronavirus disease 2019 (COVID-19) therapeutics targeting SARS-CoV-2.
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http://dx.doi.org/10.3390/microorganisms8070970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409236PMC
June 2020

Bioassay- and metabolomics-guided screening of bioactive soil actinomycetes from the ancient city of Ihnasia, Egypt.

PLoS One 2019 30;14(12):e0226959. Epub 2019 Dec 30.

Strathclyde Institute of Pharmacy and Biomedical Sciences, Faculty of Science, University of Strathclyde, Glasgow, Scotland, United Kingdom.

Literature surveys, taxonomical differences, and bioassay results have been utilized in the discovery of new natural products to aid in Actinomycetes isolate-selection. However, no or less investigation have been done on establishing the differences in metabolomic profiles of the isolated microorganisms. The study aims to utilise bioassay- and metabolomics-guided tools that included dereplication study and multivariate analysis of the NMR and mass spectral data of microbial extracts to assist the selection of isolates for scaling-up the production of antimicrobial natural products. A total of 58 actinomycetes were isolated from different soil samples collected from Ihnasia City, Egypt and screened for their antimicrobial activities against indicator strains that included Bacillus subtilis, Escherichia coli, methicillin-resistant Staphylococcus aureus and Candida albicans. A number of 25 isolates were found to be active against B. subtilis and/or to at least one of the tested indicator strains. Principal component analyses showed chemical uniqueness for four outlying bioactive actinomycetes extracts. In addition, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and dereplication study led us to further select two outlying anti-MRSA active isolates MS.REE.13 and 22 for scale-up work. MS.REE.13 and 22 exhibited zones of inhibition at 19 and 13 mm against MRSA, respectively. A metabolomics-guided approach provided the steer to target the bioactive metabolites (P<0.01) present in a crude extract or fraction even at nanogram levels but it was a challenge that such low-yielding bioactive natural products would be feasible to isolate. Validated to occur only on the active side of OPLS-DA loadings plot, the isolated compounds exhibited medium to weak antibiotic activity with MIC values between 250 and 800 μM. Two new compounds, P_24306 (C10H13N2) and N_12799 (C18H32O3) with MICs of 795 and 432 μM, were afforded from the scale-up of MS.REE. 13 and 22, respectively.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226959PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936774PMC
April 2020

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

Front Microbiol 2019 12;10:787. Epub 2019 Apr 12.

Department of Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk, Egypt.

Aims: Chemical 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.

Methods: Identification 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 antimicrobial screening using the modified version of the CLSI method, antileishmanial and antitrypanosomal activities were screened using promastigote assay, axenic amastigote assay, trypamastigotes assay and THP1 toxicity assay. The antimalarial activities against D6 (chloroquine sensitive) and W2 (chloroquine-resistant) strains of were evaluated.

Results: Seven isolated microorganisms were identified as sp., and . Chemical investigation of different extracts showed several bioactive compounds, identified as; nigragillin, 5-caboxybenzofuran and dyramide B from and actinopolysporin B from . 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 fermentation broth showed the highest activity against D6 and W2 (IC = 25.94 and 27.28 μg/mL, respectively), while two isolates and sp. RN-011 extracts showed the highest antitrypanosomal activity (IC = 0.8 and 0.96 μg/mL).

Conclusion: The River Nile could be a new source for production of promising bioactive leading compound where antimicrobial and antiparasitic activities may be correlated.
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http://dx.doi.org/10.3389/fmicb.2019.00787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476301PMC
April 2019

Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease.

Nat Commun 2019 01 18;10(1):310. Epub 2019 Jan 18.

Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.

Human gut microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we characterize gut-associated bacteria in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases. Bacterial tyrosine decarboxylases efficiently convert levodopa to dopamine, even in the presence of tyrosine, a competitive substrate, or inhibitors of human decarboxylase. In situ levels of levodopa are compromised by high abundance of gut bacterial tyrosine decarboxylase in patients with Parkinson's disease. Finally, the higher relative abundance of bacterial tyrosine decarboxylases at the site of levodopa absorption, proximal small intestine, had a significant impact on levels of levodopa in the plasma of rats. Our results highlight the role of microbial metabolism in drug availability, and specifically, that abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen of levodopa treatment in Parkinson's disease patients.
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http://dx.doi.org/10.1038/s41467-019-08294-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338741PMC
January 2019

Isolation and characterization of mercury-resistant bacteria from wastewater sources in Egypt.

Can J Microbiol 2019 Apr 11;65(4):308-321. Epub 2019 Jan 11.

c Department of Microbiology & Immunology, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Abbassia 11566, Cairo, Egypt.

An important mechanism for microbial resistance to mercury is its reduction into elemental mercury (facilitated by the merA gene). Thirty-eight microbial isolates from a variety of wastewater sources in Egypt were collected. Approximately 14 of the 38 isolates exhibited not only a high degree of tolerance to mercury (up to 160 ppm) but also a high degree of resistance to other tested heavy metals (Cu, Co, Ni, and Zn). From these 14, the 10 most resistant isolates were selected for further study and were found to include 9 Gram-negative and 1 Gram-positive bacterial strains. Multi-antibiotic-resistance profiles were detected for 6 out of the 10 selected isolates. All the tested Gram-negative isolates (n = 9) harbored a plasmid-encoded merA gene. The mercury removal effectiveness for the 10 selected isolates ranged between 50% and 99.9%, among which Stenotrophomonas maltophilia ADW10 recorded the highest rate (99.9%; at an initial mercury concentration of 20 ppm). To the best of our knowledge, this is the first study to (i) demonstrate the presence of a multimetal-resistant S. maltophilia bacterium with a high mercury tolerance capacity that would make it a suitable candidate for future bioremediation efforts in heavy-metal-polluted areas in Egypt and (ii) report Pseudomonas otitidis as one of the mercury-resistant bacteria.
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http://dx.doi.org/10.1139/cjm-2018-0379DOI Listing
April 2019

Discovery of a COX-2 selective inhibitor hit with anti-inflammatory activity and gastric ulcer protective effect.

Future Med Chem 2017 10 27;9(16):1899-1912. Epub 2017 Oct 27.

Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka, Aljouf 2014, Kingdom of Saudi Arabia.

Aim: A novel series of 2-arylimino-5-arylidenethiazolidin-4-ones 12a-n were synthesized and all the target compounds were fully characterized by IR, H NMR, C NMR, mass spectroscopy and elemental analysis. Materials & methods: All the target compounds were evaluated for their COX inhibition by enzyme immunoassay kit and in vivo anti-inflammatory activity.

Results: Tested compounds were found more potent inhibitors of COX-2 (IC = 0.54-3.14 µM) than COX-1 (IC = 4.97-11.52 µM). The ulcerogenic liability of compounds 12(d, e, f, h, k, m) was performed and showed gastric safety more than or comparable to celecoxib.

Conclusion: In addition, docking study of the most potent and selective compound 12h into COX-2 active site revealed that this target compound assumed interactions and binding pattern similar to that of as a cocrystallized ligand bromocelecoxib (S-58).
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http://dx.doi.org/10.4155/fmc-2017-0115DOI Listing
October 2017

Enhancement of the productivity of the potent bacteriocin avicin A and improvement of its stability using nanotechnology approaches.

Sci Rep 2017 09 6;7(1):10604. Epub 2017 Sep 6.

Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, Egypt.

Herein, enhancements of the yield and antimicrobial activity duration of the bacteriocin avicin A were accomplished using fractional factorial design (FFD) and layered double hydroxide (LDH) nanoparticles. Firstly, potential factors affecting bacteriocin production were selected for preliminary study. By a 2 FFD, high pH was shown to have a positive effect on avicin A yield, while temperature and duration of incubation, as well as peptone nitrogen sources all had negative effects. The highest bacteriocin production and activity (2560 BU/ml) were observed after 30 h of incubation at 30 °C, with pH adjustment at 7, and in the presence of 2 g mannitol as carbon source and 2.2 g peptone as nitrogen source. Secondly, avicin A nanocomposites with different LDH precursors were tested. Only avicin A-ZnAl-CO LDH demonstrated a potent antimicrobial activity against Lactobacillus sakei LMGT 2313 that lasted for at least 24 days, as compared to the values of 6 and 15 days observed with the free avicin A that has been stored at room temperature and at 4 °C, respectively. In conclusion, avicin A production and stability can be improved by manipulating the growth conditions and media composition, together with conjugation to LDHs.
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http://dx.doi.org/10.1038/s41598-017-10157-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587769PMC
September 2017

Exploring the Antimicrobial and Antitumor Potentials of sp. AGM12-1 Isolated from Egyptian Soil.

Front Microbiol 2017 13;8:438. Epub 2017 Mar 13.

Botany and Microbiology Department, Faculty of Science, Beni-Suef University Beni-Suef, Egypt.

The occurrence of extensive antibiotics resistant bacteria increased the demands for mining out new sources of antimicrobial agents. Actinomycetes, especially sp. have grasped considerable attention worldwide due to production of many useful bioactive metabolites. In the present study, a total of 52 actinomycetes were isolated from agricultural soil samples in Beni-Suef, Egypt. All isolates were characterized based on colony morphology, mycelium coloration, and pigment diffusion. They were screened for their capabilities to show antimicrobial activities against different indicator microorganisms, and only 20 isolates have shown significant antimicrobial activities against at least one of the tested indicator microorganisms. The isolate AGM12-1 was active against all tested microorganisms and showed a marked antitumor activity with IC 3.3 and 1.1 μg/ml against HCT-116 and HepG-2 cell lines respectively. It was genotypically characterized as sp. with the presence of PKS Π biosynthetic gene cluster. Mannitol, ammonium sulfate, pH 7, 2% inoculum size and incubation for 11 days at 30°C were the optimum conditions that used to maximize the production and hence allowed purification of one active antimicrobial compound to homogeneity using high performance liquid chromatography with a molecular mass of m/z 488.05. Nuclear magnetic resonance structural elucidation showed that this compound was a diketopiperazine derivative.
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http://dx.doi.org/10.3389/fmicb.2017.00438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346535PMC
March 2017

Nanotechnology: A Valuable Strategy to Improve Bacteriocin Formulations.

Front Microbiol 2016 16;7:1385. Epub 2016 Sep 16.

Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University Beni-Suef, Egypt.

Bacteriocins are proteinaceous antibacterial compounds, produced by diverse bacteria, which have been successfully used as: (i) food biopreservative; (ii) anti-biofilm agents; and (iii) additives or alternatives to the currently existing antibiotics, to minimize the risk of emergence of resistant strains. However, there are several limitations that challenge the use of bacteriocins as biopreservatives/antibacterial agents. One of the most promising avenues to overcome these limitations is the use of nanoformulations. This review highlights the practical difficulties with using bacteriocins to control pathogenic microorganisms, and provides an overview on the role of nanotechnology in improving the antimicrobial activity and the physicochemical properties of these peptides.
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http://dx.doi.org/10.3389/fmicb.2016.01385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026012PMC
September 2016

Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents.

Molecules 2015 Sep 14;20(9):16620-42. Epub 2015 Sep 14.

Laboratory of Growth Regulators & Department of Chemical Biology and Genetics, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR & Palacký University, Šlechtitelů 27, 783 71 Olomouc, The Czech Republic.

Sixteen new phthalimide derivatives were synthesized and evaluated for their in vitro anti-microbial, anti-oxidant and anti-inflammatory activities. The cytotoxicity for all synthesized compounds was also determined in cancer cell lines and in normal human cells. None of the target derivatives had any cytotoxic activity. (ZE)-2-[4-(1-Hydrazono-ethyl) phenyl]isoindoline-1,3-dione (12) showed remarkable anti-microbial activity. Its activity against Bacillus subtilis was 133%, 106% and 88.8% when compared with the standard antibiotics ampicillin, cefotaxime and gentamicin, respectively. Compound 12 also showed its highest activities in Gram negative bacteria against Pseudomonas aeruginosa where the percentage activities were 75% and 57.6% when compared sequentially with the standard antibiotics cefotaxime and gentamicin. It was also found that the compounds 2-[4-(4-ethyl-3-methyl-5-thioxo-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13b) and 2-[4-(3-methyl-5-thioxo-4-phenyl-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13c) had anti-oxidant activity. 4-(N'-{1-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenyl]-ethylidene}-hydrazino)-benzenesulfonamide (17c) showed the highest in vitro anti-inflammatory activity of the tested compounds (a decrease of 32%). To determine the mechanism of the anti-inflammatory activity of 17c, a docking study was carried out on the COX-2 enzyme. The results confirmed that 17c had a higher binding energy score (-17.89 kcal/mol) than that of the ligand celecoxib (-17.27 kcal/mol).
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http://dx.doi.org/10.3390/molecules200916620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331814PMC
September 2015
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