Science Advances from Beijing University published a paper: Bacterial cells form membraneless organelles through liquid-liquid separation to enhance drug resistance

Liquid-liquid phase separation (LLPS) is a key driving mechanism for many important life processes in cells

Peking University Biomedical Frontier Innovation Center (BIOPIC), Beijing Future Gene Diagnosis Advanced Innovation Center (ICG), and Bai Fan's group from the School of Life Sciences published in Molecular Cell in 2018 entitled ATP-dependent dynamic protein aggregation regulates The research paper of bacterial dormancy depth critical for antibiotic tolerance reported a new type of intracellular structure in bacteria that can dynamically aggregate and disperse-protein precipitation aggregates (aggresomes)

Figure 1: Using single-molecule high-resolution fluorescence microscopy imaging technology to study the formation mechanism of bacterial protein aggregates

The research team first selected three proteins (HslU, Kbl, AcnB) enriched in aggresomes as the research objects, and constructed fusion proteins with fluorescent labels for them

Next, the researchers selected the HslU protein with the fastest response speed as the biomarker of aggresomes, and explored the spatiotemporal dynamic characteristics of aggresomes formation through single-molecule fluorescence tracking

Figure 2: Liquid-liquid separation drives the formation of bacterial protein precipitation aggregates

Subsequently, the research team used the Individual-Protein-Based Model (IPBM) to simulate the process of gradual aggregation of protein precipitation droplets and phase separation to form larger membraneless organelles

Figure 3: The mathematical model simulates the fine process of aggresomes formation

Finally, the research team proved that reducing intracellular ATP in a variety of common bacteria can induce the production of aggresomes, suggesting that the formation of aggresomes may be a universal response of bacteria against external pressure

This study expands the application of the liquid-liquid phase separation mechanism in prokaryotes, and finds that bacterial cells use phase separation to dynamically adjust the temporal and spatial distribution of proteins in the cytoplasm, and enhance the bacteria's ability to resist external environmental pressure and antibiotic resistance

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