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In vitro studies on a natural lantibiotic, paenibacillin: A new-generation antibacterial drug candidate to overcome multidrug-resistance.

08:00 EDT 27th March 2019 | BioPortfolio

Summary of "In vitro studies on a natural lantibiotic, paenibacillin: A new-generation antibacterial drug candidate to overcome multidrug-resistance."

The alarming burden of antibiotic-resistance in nosocomial pathogens warrants the discovery and development of new and effective antimicrobial compounds. Small cationic antimicrobial peptides (CAMPs) seem to be a promising therapeutic alternative to fight multi-drug resistance. In the present study, we investigated the in vitro potential of a previously reported lantibiotic, paenibacillin from the clinical perspective. We isolated, purified and characterized an antimicrobial peptide named M152-P4 from a mud isolate. We determined its susceptibility in clinical isolates of Staphylococcus aureus and Enterococcus sp. We performed time-kill kinetics, resistance studies, probable mode of action studies, haemolytic activity and mammalian cytotoxicity. The peptide was identified as paenibacillin based on mass spectroscopy data, amino acid analysis and biosynthetic gene cluster. The peptide had potent antibacterial activity against the Gram-positive pathogens tested with MIC from 0.1 to 1.56 µM. It appeared very challenging for S. aureus to develop resistance towards this compound. Also, the peptide penetrated the outer layer of bacteria and depolarized the membrane completely by creating pores in the plasma membrane with better potential than nisin. The peptide showed no haemolysis up to 60 µM and IC on mammalian cell lines was more than 100 µM. Here, we highlight the excellent antibacterial properties of paenibacillin in clinically relevant pathogens. It is stable in the presence of serum and found to be non-haemolytic and non-cytotoxic even above the therapeutic concentration. Further efforts on toxicity and in vivo efficacy are necessary to develop it as a next-generation therapeutic drug to overcome multidrug-resistance in Gram-positive pathogens.

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This article was published in the following journal.

Name: International journal of antimicrobial agents
ISSN: 1872-7913
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