Metabolic regulation of bacterial cell growth Grant uri icon

abstract

  • Tight regulation of cell envelope synthesis is essential to bacterial fitness, as envelope integrity is crucial to its roles in mediating molecular transport, defining cell shape and size, and protecting the cell from osmotic stress. Unsurprisingly, the envelope is also the target of the most prescribed class of antibiotics (beta-lactams), which effectively inhibit growth and/or cause cell lysis by perturbing the envelope's peptidoglycan (PG) component. Pathogens also evolve resistance mechanisms to these drugs, so there is a continuous need to develop new antibiotic arsenals. Effectively tackling this challenge requires a thorough understanding of the molecular mechanisms governing cell envelope synthesis, and many important players have been identified. However, the regulation of cell envelope synthesis during growth remains poorly understood. Many bacteria utilize actin-like proteins to direct synthesis of the peptidoglycan component of the cell envelope. MreB and MreB-like proteins are thought to act as scaffolds, guiding the localization and activity of key PG synthesizing proteins during cell elongation. Despite their critical role in viability and cell-shape maintenance, very little is known about how the activity of MreB family proteins is regulated. We have identified a novel factor that interfaces with Mbl, an MreB paralog in Bacillus subtilis, and in in this proposal we will investigate the molecular basis for the observed interaction. The proposed studies will inform a more complete picture of the mechanisms underlying cell envelope synthesis by providing important missing information regarding the regulation of MreB and MreB-like proteins.

date/time interval

  • 2019 - 2024