A bacterium’s cell wall—a mesh-like peptidoglycan layer—must expand and split in perfect coordination for the cell to grow and divide, yet the molecular machinery that drives this process remains largely unknown. This matters because the cell wall is the frontline target of many antibiotics and immune defences like lysozyme. As resistance spreads, pathogens such as *Pseudomonas aeruginosa* and *Helicobacter pylori* cause increasingly hard-to-treat infections. Without a clear picture of how the wall is built and broken down, designing new drugs that outflank resistance is guesswork. The researchers will map the multi-enzyme complexes that synthesise and remodel the wall in *Escherichia coli*, then extend the work to three major Gram-negative pathogens. They aim to reveal how the cytoskeleton regulates wall growth and how that growth is synchronised with the construction of the inner and outer membranes. This is fundamental science. It will not produce a new antibiotic tomorrow. But it will establish the molecular assays and structural targets needed to screen for compounds that block wall assembly in resistant bacteria—a prerequisite for any future drug. Past work on cell-wall enzymes, for instance, directly enabled the development of carbapenem antibiotics.
View original technical description
The essential cell wall peptidoglycan layer protects the bacterial cell from rupture due to its turgor and maintains its cell shape. Human cells sense peptidoglycan fragments released by growing or lysing bacteria triggering an immune response. Peptidoglycan and its biosynthesis are targeted by components of the innate immune system, including lysozyme, and important antibiotics. However, many pathogens have become resistant to antimicrobial compounds and enzymes and cause serious infections in humans and animals. How the cell wall grows when a bacterial cell elongates and divides is a fundamental but poorly understood process. Hypothetical multi-enzyme complexes catalyse the growth of the stress-bearing peptidoglycan layer, regulated by the cytoskeleton and coordinated with the growth of the other cell envelope layers, but the underlying molecular details are largely unknown. The proposed research will focus on cell wall growth in Gram-negative bacteria and has the following ke y goals: in the model bacterium Escherichia coli we aim to (i) determine the molecular mechanisms of peptidoglycan growth and its regulation by cytoskeletal elements and (ii) find out how peptidoglycan growth is coordinated with the synthesis of the inner and outer membranes. Further, in Pseudomonas aeruginosa, Burkholderia spp. and Helicobacter pylori we will (iii) investigate important aspects of peptidoglycan growth specific to other Gram-negative pathogens. Together, these studies should not only provide fundamental insights into bacterial cell wall growth but they should establish novel assays and targets for antimicrobial drug discovery.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know