Background: Bacterial resistance to antibiotics is an overwhelming solemn challenge worldwide. This calls for exploratory for novel origins of antibacterial drugs. Tetracycline resistance is mediated via mutations within the ribosomal binding site and/or the attainment of mobile genetic elements bearing tetracycline-specific resistance genes.The aim of the study: Design of novel antimicrobial tetracycline analogs and screening of their in vitro antibacterial activity. Methodology: Our study type was a screening experimental study. In this work, in vitro antimicrobial novel tetracycline, analog activity semi-synthetically produced from Streptomyces species was evaluated by standard agar dilution technique determining their minimum inhibitory concentrations (MICs) of growth of different pathogenic bacteria in Egypt. Tetracycline was purified by aqueous two-phase systems consisting of cholinium-based salts and polyethylene glycol, then modified by chemo-informatics. The addition of electron-with drawing Iodide anion at carbon 7 position to tetracycline originated tetracycline analog B (iodocycline). Results and discussioniodocycline(tetracycline analog B) antibiotic was a more active bacteriostatic antibacterial agent than tetracycline but demonstrated less bacterial resistance. Tetracycline analog B showed MICs of less than 10 micrograms/ml for bacterial growth which reflected its powerful antimicrobial activity in a comparison with the chloramphenicol prototype antibiotic.

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Background: Auxotrophic cancers are a leading cause of cancer-related deaths in the world. Because certain cancers are arginine amino acid auxotrophs, the Depletion of extracellular arginine using arginine deiminase (ADI) could be exploited to target such cancers. ADI is a potential anticancer agent against arginine auxotrophic cancers. It catalyzed the hydrolysis of L-arginine to L-citrulline and ammonia. Purpose of the research: Our study aimed to find new sources of bacterial arginine deiminases from different soil environments in Egypt and their production as anticancer agents by recombinant DNA technology.Methodology: This study was designed to screen for ADI-producing bacterial species using a simple and convenient method using metallo-arginine agar selective medium (MAA) and the Nesslarization assay. The isolated samples were characterized based on morphological features, biochemical reactions, and DNA probe hybridization. The antitumor activity of ADI was analyzed by MTT cell viability assay using various cancer cell lines. Results: Bacillus cereus strain AH173 was the major ADI-producing bacterial isolate from various soil environments in Egypt. The enzyme of interest showed excellent anticancer activity against L-arginine amino acid auxotrophic cancers. The molecular weight of ADI was 48 kDa. The Km and Vmax values of ADI were 8.75 mmol/L and 8.78 µmol/min. The IC50 for bacterial ADI was 2.42 U/ml for liver cancer cell lines, 2.17 U/ml for melanoma cancer cell lines, 4.63 U/ml for colon cancer cell lines, and 4.53 U/ml for lung adenocarcinoma cell line (Calu-3), 3.12 vs PANC-1 pancreatic cancer cell line, 3.77 vs RCC4 renal cancer cell line and 4.37 U/ml against a heart cancer line (HL1). The selectivity index of bacterial ADI against cancer cell lines was as the following: 3.93 vs (JHH4) liver cancer cell lines, 3.24 vs (IM1215) colon cancer cell lines, 3.61 vs (UPMM3) melanoma cancer cell lines, 3.18 vs (Calu-3) lung adenocarcinoma cell lines, 3.07 vs PANC-1 pancreatic cancer cell line, 3.81 vs RCC4 renal cancer cell line and 3.75 vs (HL1) heart cancer cell line. Conclusion: In this study, a new bacterial source for the production of ADI as an anticancer agent from various soil environments in Egypt was characterized.

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