SimCells are a very exciting way of delivering toxins in a targeted fashion to antibiotic resistant bacteria. It reminds me of my past synthetic biology research in an adjacent area. Love this approach!

In addition to the T6SS system, close contact between attacker and prey cells also allows local delivery of high concentrations of antimicrobial compounds around the targeted cells. To exploit this, we introduced a constitutively expressed salicylate hydroxylase (NahG) into our system (SI Appendix, Fig. S8 A), which catalyzes the conversion of acetylsalicylic acid (aspirin) into catechol (70, 71) (Fig. 4 A). Catechol has a broad-spectrum antimicrobial activity (67 – 69) by generating hydrogen peroxide (H₂O₂) through auto-oxidation processes (SI Appendix, Fig. S7 A –C), during which catechol polymerizes to form cross-linked polymers without external catalysts (80 – 83) (Fig. 4 A). When 800 μM aspirin 84)] was added to the parental cell and SimCell cultures, the filtered supernatants from overnight NahG+ cultures exhibited a dark-brown color (SI Appendix, Fig. S8 B), which is associated with the oxidation products of catechol. The collected supernatants showed a significant inhibitory effect on bacterial cell growth (SI Appendix, Fig. S8 B and C). These results indicate the generation, permeability, and extracellular antimicrobial activity of SimCell-produced catechol and associated production of H₂O₂.

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Biomolecular condensates are tiny, droplet-like structures made up of molecules that help organize key processes in living organisms. Because they are so small and constantly changing, it has been difficult for scientists to measure their physical properties or control how they behave. Leiden researchers at the Mashaghi Lab have now discovered a surprising new way to shape and control tiny droplets of molecules found in living organisms. The breakthrough could lead to smarter biomaterials, improve drug delivery and even new insights into the emergence of life on Earth. The work is published in Nature Communications.

“Our lab works at the interface of biophysics, molecular engineering and medicine,” says Alireza Mashaghi. “We explore how molecular interactions drive the emergent properties of biological materials.”

Inside the condensates, Mashaghi and his team triggered a reaction normally associated with DNA damage from UV light (like that seen in skin cancer). Known as thymine dimer formation, this process causes two neighboring thymine bases to bond together. By harnessing this reaction as a molecular “switch” within the condensates, the researchers were able to alter the internal connectivity of the molecules, allowing them to control how the condensates behave.