Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt

Version 1 : Received: 2 May 2024 / Approved: 7 May 2024 / Online: 7 May 2024 (10:05:59 CEST)

How to cite: Kassab, M. Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt. Preprints 2024, 2024050350. https://doi.org/10.20944/preprints202405.0350.v1 Kassab, M. Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt. Preprints 2024, 2024050350. https://doi.org/10.20944/preprints202405.0350.v1

Abstract

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Keywords

Myxopyronin B; microbial; antibiotic; resistance; myxobacteria

Subject

Chemistry and Materials Science, Medicinal Chemistry

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