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Best, E.

Publications and source records attributed to Best, E..

2 recordsLinked to original sources

Discovery and biosynthetic assessment of Streptomyces ortus sp nov. isolated from a deep-sea sponge

The deep sea is known to host novel bacteria with the potential to produce a diverse array of undiscovered natural products. Understanding these bacteria is thus of broad interest in ecology and could also underpin applied drug discovery, specifically in the area of antimicrobials. Here, we isolate a new strain of Streptomyces from the tissue of the deep-sea sponge Polymastia corticata collected at a depth of 1869 m from the Gramberg seamount in the Atlantic Ocean. This strain, which was given the initial designation A15ISP2-DRY2T, has a genome size of 9.29 Mb with a GC content of 70.83%. Phylogenomics determined that A15ISP2-DRY2T represents a novel species within the genus Streptomyces as part of the Streptomyces aurantiacus clade. The biosynthetic potential of A15ISP2-DRY2T was assessed relative to other members of the aurantiacus clade via comparative gene cluster family (GCF) analysis. This revealed a clear congruent relationship between phylogeny and GCF content. A15ISP2-DRY2T contains six unique GCFs absent elsewhere in the clade. Culture-based assays were used to demonstrate the antibacterial activity of A15ISP2-DRY2T against two drug-resistant human pathogens. We thus determine A15ISP2-DRY2T to be a novel bacterial species with considerable biosynthetic potential and propose the systematic name Streptomyces ortus sp. nov. Impact StatementThe Streptomyces genus has contributed more to our antibiotic arsenal than any other group of bacteria or fungi. Despite decades of exploration, global analysis has suggested they still possess more undiscovered biosynthetic diversity than any other bacterial group. Isolating novel species of Streptomyces is therefore a priority for antibiotic discovery. Here we isolate a novel strain from a deep-sea sponge and use comparative cluster analysis to identify six biosynthetic clusters unique to our deep-sea strain. This work demonstrates the utility of continuing to isolate novel Streptomyces strains for antibiotic discovery and, for the first time, we used species tree-gene cluster tree reconciliation to assess the contribution of vertical evolution on the biosynthetic gene cluster content of Streptomyces.

genomics↗

Chitosan-coated carboxylic acids show antimicrobial activity against antibiotic-resistant Gram-negative and positive pathogens

Antibiotic resistance in bacteria is suggested to be the greatest risk to human health, but new agents are not being brought to market as the rapid evolution of resistance to them means that drug development costs cannot be recouped. Fatty acids have been proposed as a new generation of antibiotics, but toxicity and poor absorption has meant that their use has been impractical in the past. Chitosan has been used to encapsulate other agents as nanoparticles, but has not been used with fatty acids. Here we show that chitosan can be modified to direct fatty acids towards Gram-positive or negative bacteria so that they exert antimicrobial effects. We show that fatty acids work as effective antibiotics in vitro and in vivo, with activity against extremely drug resistant pathogens. Bacteria exposed to them do not develop resistance to these agents, and they are not toxic to mammalian cells. Activity was seen against salmonellosis and C. difficile infection in animal models. Our results demonstrate that fatty acids formulated as chitosan nanoparticles are effective antibiotics, and can be used for a long period of time without resistance developing. This suggests that the usage of fatty acids coated in this manner could be sold in sufficient quantities to recoup its development costs, overcoming this barrier. These agents would form a new class of antibiotics, with the novel property of lack of bacterial resistance.

microbiology↗