SAMN37000867
External Id
IBL, Leiden University
INSDC center name
2024-02-16T12:47:07.640Z
INSDC first public
2024-02-16T12:47:07.640Z
INSDC last update
live
INSDC status
Microbe, viral or environmental
NCBI submission model
Microbe.1.0
NCBI submission package
ERS18335256
SRA accession
2018-06-29
collection_date
The escalating prevalence of multidrug-resistant bacteria, coupled with a strong decline in antibiotic discovery and development, presents a serious challenge in effectively addressing the threat posed by these pathogens. In this study, we present the discovery of the novel lipopeptide antibiotics tridecaptin A5 and tridecaptin D, using an extensive global genome-mining strategy. Through bioinformatically guided organic synthesis and comprehensive antibacterial assays, we demonstrate that synthetic analogues Oct-TriA5 and Oct-TriD exhibit unusual bioactivity spectra not commonly associated with tridecaptins. Surprisingly, Oct-TriD is active against Gram-positive Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium with an MIC range of 4 to 8 ug/mL and possesses moderate activity against Gram-negative pathogens. Interestingly, a single amino acid substitution at position 9 from Phe in Oct-TriA1 to Trp in Oct-TriA5 further expanded the antibacterial spectrum of activity to include both Gram-negative and Gram-positive bacteria. Subsequent screening of analogues incorporating substitutions at position 9 resulted in the identification of Oct-His9, a potent congener with reduced hemolytic and cytotoxic properties and exceptional efficacy against Pseudomonas aeruginosa. These findings underscore the promising potential of tridecaptin analogues as viable alternatives in combatting antibiotic-resistant bacterial pathogens.
description
USA: Nebraska, Dunbar
geo_loc_name
Zea mays
host
root
isolation_source
Paenibacillus peoriae
http://purl.obolibrary.org/obo/NCBITaxon_59893
organism
tissue sample
sample_type
JJ21
strain
Genome mining-driven discovery of new tridecaptin analogues with enhanced bioactivity
title