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Extracellular matrix chemistry tunes bacterial biofilm metabolism and optimizes fitness

Li, J.; Squyres, G. R.; Duong, K.; Reichhardt, C.; Newman, D. K.; Parsek, M. R.

2025-09-18 microbiology
10.1101/2025.09.18.677115 bioRxiv
Show abstract

Chemically complex extracellular matrices define cellular microenvironments and shape cell behavior. We hypothesized a composition-properties-function relationship in these natural living materials, where interactions among matrix components govern material properties and cellular physiology. Using Pseudomonas aeruginosa biofilms as a model system, we show that electrostatic interactions between the cationic polysaccharide Pel and extracellular DNA (eDNA) regulate retention of pyocyanin (PYO), a redox-active metabolite that supports anaerobic metabolism via extracellular electron transfer (EET). Biofilm-mimetic hydrogels and natural biofilms revealed that altering Pels charge via pH adjustment or chemical acetylation, or tuning the Pel:eDNA ratio, predictably modulates PYO retention and EET efficiency. Functionally, a lower Pel:eDNA ratio enhances metabolism under oxygen limitation, whereas a higher ratio promotes survival under antibiotic stress. These findings highlight how matrix chemistry encodes tunable material properties that confer biofilm fitness advantages and establish a materials-based framework for understanding extracellular matrices in multicellular communities.

Published in Proceedings of the National Academy of Sciences (predicted rank #4) · training set

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