Purification and biological activity of natural variants synthesized by tridecaptin M gene cluster and in vitro drug-kinetics of this antibiotic class.
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
Purification and biological activity of natural variants synthesized by tridecaptin M gene cluster and in vitro drug-kinetics of this antibiotic class.
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| Creator |
Jangra, Manoj
Kaur, Manpreet Podia, Mansi Tambat, Rushikesh Singh, Vidhu Chandal, Nishtha Mahey, Nisha Maurya, Navdezda Nandanwar, Hemraj |
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| Subject |
QR Microbiology
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| Description |
The flexibility of the adenylation domains of non-ribosomal peptide synthetases (NRPSs) to different substrates creates a diversity of structurally similar peptides. In the present study, we investigated the antimicrobial activity of different natural variants synthesized by tridecaptin M gene cluster and performed the in vitro drug kinetics on this class. The natural variants were isolated and characterized using MALDI-MS and tandem mass spectrometry. All the peptides were studied for their antimicrobial activity in different pathogens, including colistin-resistant bacteria, and for haemolytic activity. Furthermore, in vitro drug kinetics was performed with tridecaptin M (or M, the major product of the gene cluster). The natural variants displayed a varying degree of bioactivity with M showing the most potent antibacterial activity (MIC, 1-8 µg/ml), even against A. baumannii and P. aeruginosa strains. The in vitro kinetic studies revealed that tridecaptin M at a concentration of 16 µg/ml eradicated the bacteria completely in high-density culture. The compound demonstrated desirable post-antibiotic effect after two-hour exposure at MIC concentration. We also observed the reversal of resistance to this class of antibiotics in the presence of carbonyl cyanide m-chlorophenyl hydrazine (CCCP). Altogether, the study demonstrated that tridecaptins are an excellent drug candidate against drug-resistant Gram-negative bacteria. Future studies are required to design a superior tridecaptin by investigating the interactions of different natural variants with the target.
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| Publisher |
Nature Publishing Group
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| Date |
2019-12-11
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Article
PeerReviewed |
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| Relation |
http://dx.doi.org/10.1038/s41598-019-54716-8
http://crdd.osdd.net/open/2520/ |
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| Identifier |
Jangra, Manoj and Kaur, Manpreet and Podia, Mansi and Tambat, Rushikesh and Singh, Vidhu and Chandal, Nishtha and Mahey, Nisha and Maurya, Navdezda and Nandanwar, Hemraj (2019) Purification and biological activity of natural variants synthesized by tridecaptin M gene cluster and in vitro drug-kinetics of this antibiotic class. Scientific reports, 9 (1). p. 18870. ISSN 2045-2322
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