ORCID Profile
0000-0002-7241-2835
Current Organisations
Gdańsk Medical University
,
Ain Shams University
,
Karolinska Institutet
,
Homerton University Hospital
,
Kuwait Oil Company
,
Preliminary Program for European University Diploma in Laparoscopy
,
Ahmadi Hospital
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Publications
Antibacterial effects assessment on some livestock pathogens, thermal stability and proposing a probable reason for different levels of activity of thanatin
Publisher: Springer Science and Business Media LLC
Date: 25-05-2021
DOI: 10.1038/S41598-021-90313-4
Abstract: There is a continuing need to prevent the increasing use of common antibiotic and find the replacement to combat the drug/antibiotic resistant bacteria such as antimicrobial peptides (AMPs) such as thanatin peptide. In this study, recombinant thanatin peptide was expressed in the HEK293 cell line. Then the antimicrobial properties of this peptide on some poultry and farm animal’s pathogen strains were assessed. The thermal-stability of thanatin was predicted in various temperatures through in silico analysis. Afterwards, according to Minimum Inhibitory Concentration (MIC) results, Escherichia coli and Pseudomonas aeruginosa were chosen to test the hypothesis of LptA/LptD–thanatin interaction, computationally. Relative amino acid sequences and crystallography structures were retrieved and missed tertiary structures were predicted. The interaction of thanatin with LptA and LptD of Escherichia coli and Pseudomonas aeruginosa were analyzed subsequently. The antibacterial activity of thanatin peptide was evaluated between 6.25 and 100 μg/mL using minimum inhibitory concentration. Also, the amounts of minimum bactericidal concentrations (MBC) were between 12.5 and 200 μg/mL. The bioinformatics analysis followed by the in vitro assessment, demonstrated that thanatin would be thermally stable in the body temperature of poultry and farm animals. Thanatin could penetrate to the outer membrane domain of LptD in Escherichia coli and it could block the transition path of this protein while the entrance of LptD in Pseudomonas aeruginosa was blocked for thanatin by extra residues in comparison with Escherichia coli LptD. In addition, the quality of interaction, with regard to the number and distance of interactions which leads to higher binding energy for thanatin and LptD of Escherichia coli was much better than Pseudomonas aeruginosa. But the site and quality of interaction for thanatin and LptA was almost the same for Escherichia coli and Pseudomonas aeruginosa. Accordingly, thanatin can prevent the assembly of LptA periplasmic bridge in both pathogens. The antibacterial and thermal stability of the thanatin peptide suggested that thanatin peptide might serve as a natural alternative instead of common antibiotics in the veterinary medicine. The outcome of this in silico study supports the MIC results. Therefore, a probable reason for different level of activity of thanatin against Escherichia coli and Pseudomonas aeruginosa might be the quality of LptA/LptD–thanatin interaction.
Improvement of the performance of anticancer peptides using a drug repositioning pipeline
Publisher: Wiley
Date: 14-11-2022
Abstract: The use of anticancer peptides (ACPs) as an alternative/complementary strategy to conventional chemotherapy treatments has been shown to decrease drug resistance and/or severe side effects. However, the efficacy of the positively‐charged ACP is inhibited by elevated levels of negatively‐charged cell‐surface components which trap the peptides and prevent their contact with the cell membrane. Consequently, this decreases ACP‐mediated membrane pore formation and cell lysis. Negatively‐charged heparan sulphate (HS) and chondroitin sulphate (CS) have been shown to inhibit the cytotoxic effect of ACPs. In this study, we propose a strategy to promote the broad utilization of ACPs. In this context, we developed a drug repositioning pipeline to analyse transcriptomics data generated for four different cancer cell lines (A549, HEPG2, HT29, and MCF7) treated with hundreds of drugs in the LINCS L1000 project. Based on previous studies identifying genes modulating levels of the glycosaminoglycans (GAGs) HS and CS at the cell surface, our analysis aimed at identifying drugs inhibiting genes correlated with high HS and CS levels. As a result, we identified six chemicals as likely repositionable drugs with the potential to enhance the performance of ACPs. The codes in R and Python programming languages are publicly available in github.com/ElyasMo/ACPs_HS_HSPGs_CS . As a conclusion, these six drugs are highlighted as excellent targets for synergistic studies with ACPs aimed at lowering the costs associated with ACP‐treatment.
Treatment of iron deficiency and iron deficiency anemia with intravenous ferric carboxymaltose in pregnancy
Publisher: Springer Science and Business Media LLC
Date: 08-05-2018
Related Organisations
Gorgan University Of Agricultural Sciences And Natural Resources
Location: Iran (Islamic Republic of)
Homerton University Hospital
Location: United Kingdom of Great Britain and Northern Ireland
Preliminary Program For European University Diploma In Laparoscopy
Location: Egypt
Related Funding Activities
No related grants have been discovered for Ibrahim Abdelazim.