Extracellular vesicle packaging of a supercluster-encoded antimicrobial combination with enhanced potency against fungal biofilms
- 1University of Waterloo
Abstract
Bacterial specialized metabolites are bioactive compounds that have been mined extensively as antibacterials, antifungals, and other drugs. They are widely used as experimental probes of complex biological systems. Since their discovery, their functional characteristics have typically been investigated as single, soluble compounds. The discoveries in this work expand this model. First, we report the co-packaging in extracellular vesicles (EVs) of two specialized metabolite complexes, candicidin and antimycin A, the products of a supercluster of biosynthetic genes, by a Streptomyces soil isolate. Secondly, we report that the products of this supercluster have synergistic antimicrobial activity against fungal biofilms, whereas biofilms are tolerant to the individual compounds. Finally, we show that co-packaging these compounds in EVs ensures simultaneous delivery with enhanced potency. This research advances understanding of the elegant complexity that shapes the evolution and function of bacterial specialized metabolites. In particular, the enhanced antibiofilm activity of co-packaged metabolites compared to individual soluble compounds is notable given the relevance of biofilms to microbial ecology and to pathogenesis. Our work supports the evolution of coordinated activity of specialized metabolites to counter conditional environmental challenges, and highlights co-packaging in EVs as one mechanism for secretion and co-delivery of combinations of bioactive molecules.
Related
- Combination of enhanced gene activation and cell death causes lethal inflammatory pulmonary fibrosis
- A biomimetic SPARC platform coupling adaptor recruitment and BRS-Lck condensation for enhanced NK/T cell combination therapy
- Enhanced Antimicrobial Potency and Therapeutic Index of a Defined C12 Quaternary Ammonium Compound
- Constructing co-assembly derived smart lipid nanoparticles for enhanced antimicrobial potency with plant growth-promoting potential
- Upcycling banana peduncle fibers into mycelium-based composites for sustainable packaging and thermal insulation
BibTeX
@misc{meyer2026extracellular,
title = {{Extracellular vesicle packaging of a supercluster-encoded antimicrobial combination with enhanced potency against fungal biofilms}},
author = {K. J. Meyer and V. Chow and E. Piliouras and Y. Lee and H. Ostapska and O. Ojeda Valencia and I. Ben Makhlouf and N. Robbins and L. E. Cowen and J. R. Nodwell},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.25.761712},
url = {https://www.biorxiv.org/content/10.64898/2026.10.25.761712v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Extracellular vesicle packaging of a supercluster-encoded antimicrobial combination with enhanced potency against fungal biofilms
AU - K. J. Meyer
AU - V. Chow
AU - E. Piliouras
AU - Y. Lee
AU - H. Ostapska
AU - O. Ojeda Valencia
AU - I. Ben Makhlouf
AU - N. Robbins
AU - L. E. Cowen
AU - J. R. Nodwell
PY - 2026
DA - 2026/10/25
PB - bioRxiv
DO - 10.64898/2026.10.25.761712
UR - https://www.biorxiv.org/content/10.64898/2026.10.25.761712v1
AB - Bacterial specialized metabolites are bioactive compounds that have been mined extensively as antibacterials, antifungals, and other drugs. They are widely used as experimental probes of complex biological systems. Since their discovery, their functional characteristics have typically been investigated as single, soluble compounds. The discoveries in this work expand this model. First, we report the co-packaging in extracellular vesicles (EVs) of two specialized metabolite complexes, candicidin and antimycin A, the products of a supercluster of biosynthetic genes, by a Streptomyces soil isolate. Secondly, we report that the products of this supercluster have synergistic antimicrobial activity against fungal biofilms, whereas biofilms are tolerant to the individual compounds. Finally, we show that co-packaging these compounds in EVs ensures simultaneous delivery with enhanced potency. This research advances understanding of the elegant complexity that shapes the evolution and function of bacterial specialized metabolites. In particular, the enhanced antibiofilm activity of co-packaged metabolites compared to individual soluble compounds is notable given the relevance of biofilms to microbial ecology and to pathogenesis. Our work supports the evolution of coordinated activity of specialized metabolites to counter conditional environmental challenges, and highlights co-packaging in EVs as one mechanism for secretion and co-delivery of combinations of bioactive molecules.
ER -