Assembly of Bacterial Cell Surface

Bacterial cell envelopes are complex, multilayered structures composed of one or two membranes and diverse glycopolymers. Their biogenesis is tightly coordinated with cell growth, division and morphogenesis, requiring precise spatial and temporal control to maintain cellular homeostasis. Despite their fundamental importance for bacterial physiology, the mechanisms governing envelope assembly are not completely understood and represent a major challenge in microbiology.

The team BacSurf aims to uncover the molecular and cellular mechanisms that control bacterial envelope assembly. Our research approaches this question from a unique perspective by focusing on two key metabolic pathways:

• Polyprenyl phosphate lipid (Pren-P) recycling, universally required as lipid carriers for the biosynthesis of diverse bacterial envelope glycopolymers.
• The mycoloylation network, which orchestrates outer membrane formation and the assembly of the peptidoglycan–arabinogalactan–mycolic acid complex in Mycobacteriales.
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Pren-P lipid carriers play a central by enabling the translocation of glycopolymer precursors across the plasma membrane. These precursors are covalently attached to Pren-P and transported to the cell surface, where polymer assembly takes place. After transfer of the building blocks, the lipid carrier is released at the outer face of the membrane and must be recycled to sustain continuous cell wall synthesis. The BacSurf team identifies and characterizes the proteins involved in Pren-P recycling and investigates how this process is coordinated with cell growth and division. Through integrative approaches combining molecular biology, biochemistry, and cell biology, we aim to define how this essential recycling pathway supports bacterial envelope biogenesis.

The Mycoloylation network constitutes the central organizing pathway for the biogenesis of Mycobacteriales cell envelopes, allowing the assembly of their distinctive outer membrane and the biosynthesis of the peptidoglycan-arabinogalactan-mycolic acid complex.  Mycolic acids are synthetized and esterified on trehalose in the cytoplasm before being translocated towards the extracytoplasmic space, where they are distributed on various cell envelope acceptors by a family of Mycoloyltransferase enzymes. However, the functional significance of an enzymatic plurality remains unclear and likely plays a critical role in this pathway. Understanding how this network operates and is regulated constitutes a central objective of BacSurf.

In line with these pathways, and more generally with the bacterial cell surfaces, we also investigate mechanisms of antibiotic resistance related with cell envelope biogenesis and develop innovative antibacterial strategies targeting bacterial surfaces.