Abstract
Antimicrobial resistance in Gram-negative pathogens represents a global threat to human health. This study determines the antimicrobial potential of a taxonomically and geographically diverse collection of 263 Burkholderia (sensu lato) isolates and applies natural product dereplication strategies to identify potentially novel molecules. Antimicrobial activity is almost exclusively present in Burkholderia sensu stricto bacteria and rarely observed in the novel genera Paraburkholderia, Caballeronia, Robbsia, Trinickia, and Mycetohabitans. Fourteen isolates show a unique spectrum of antimicrobial activity and inhibited carbapenem-resistant Gram-negative bacterial pathogens. Dereplication of the molecules present in crude spent agar extracts identifies 42 specialized metabolites, 19 of which represented potentially novel molecules. The known identified Burkholderia metabolites include toxoflavin, reumycin, pyrrolnitrin, enacyloxin, bactobolin, cepacidin, ditropolonyl sulfide, and antibiotics BN-227-F and SF 2420B, as well as the siderophores ornibactin, pyochelin, and cepabactin. Following semipreparative fractionation and activity testing, a total of five potentially novel molecules are detected in active fractions. Given the molecular formula and UV spectrum, two of those putative novel molecules are likely related to bactobolins, and another is likely related to enacyloxins. The results from this study confirm and extend the observation that Burkholderia bacteria present exciting opportunities for the discovery of potentially novel bioactive molecules.
Highlights
Antimicrobial resistance has become one of the most important threats to global health, causing at least 700,000 deaths worldwide each year [1]
A diverse collection of 263 Burkholderia isolates was selected from the BCCM/LMG
To explore the antimicrobial potential of Burkholderia sensu lato bacteria, a taxonomically and geographically diverse collection of isolates was screened for antagonistic activity against S. aureus ATCC 29213, A. baumannii LMG 10520, and C. albicans SC5314
Summary
Antimicrobial resistance has become one of the most important threats to global health, causing at least 700,000 deaths worldwide each year [1]. Drug discovery efforts commonly suffer from low success rates, due to a lack of chemical diversity in the synthetic compound libraries. Such synthetic compounds are much less likely to become antimicrobial drugs compared to microbial metabolites [3]. Since the majority of currently known antibiotics are produced by actinomycetes, these organisms have been the main focus of drug discovery programs [5]. Actinomycetes are not the only organisms with considerable genomic potential for specialized metabolite production, since recent bioinformatics analyses showed that specialized metabolite biosynthetic gene clusters are widespread in the genomes of Burkholderia bacteria [6,7,8]
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