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Understanding the role of molecular and cellular structures in gut acetogens as key adaptive strategies for survival in a competitive microbiome.

Subject Area Metabolism, Biochemistry and Genetics of Microorganisms
Term since 2025
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 564324550
 
The human gut microbiome is a highly complex ecosystem that plays a key role in the breakdown of organic matter. It enables humans to utilise carbohydrates and polymers that would otherwise be indigestible. In recent years, large-scale microbiome studies have significantly advanced our understanding of the composition, distribution and metabolic functions of gut microbes and their potential benefits to the human host. It has been found that although acetogens are a small numerical component of the human gut microbiome, estimated to comprise up to 5% of the total gut microbiome and contribute to the well-being of human gut. Their metabolic activity, the production of products like succinate lactic acid, and acetate, helps them plays a indispensable role in maintaining metabolic balance and gut ecology. Acetogens use the efficient Wood-Ljungdahl pathway (WLP) to convert CO₂ to acetate during lithoautotrophic growth on H₂ and CO₂. In the gut, they can also grow organoheterotrophically on different nutrients and mixotrophically by using gases and complex sugars simultaneously. Beyond the WLP, gut acetogens display diverse metabolic strategies, including the use of bacterial microcompartments (BMCs) to produce ethanol. However, despite their importance for a healthy microbiome and host health, gut acetogens remain an under-explored area of research, leaving significant gaps in our knowledge of their physiology, interactions and unique adaptations within the gut microbiome. Therefore, moving beyond conventional approaches to a deeper exploration of the individual organisms within this community is essential to fully appreciate their role in the human microbiome. By visualising the undisturbed interior of the cells using cryo-electron tomography, we have found that these unique microbes display a level of structural and functional sophistication that sets them apart from typical bacteria. We have identified several molecular and cellular structures such as enzyme-decorated nanowires, enzyme filaments, and BMCs. In contrast to previous studies that have relied solely on genomic and transcriptional analyses, this research will take an integrative approach. We plan to incorporate scale-bridging imaging techniques to reveal the nature and function of these structures and their role in enhancing microbial efficiency. In this project we aim to identify and characterize these filamentous structures, study the ultrastructure of BMCs and understand how these cellular assemblies remodel under different defined growth and mixotrophic conditions, including in co-culture with a minimal defined community. These insights will be crucial for understanding the role of acetogens within the microbiome and their beneficial impact on human health.
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