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Demonstration of the role of cell wall homeostasis in growth and the action of bactericidal antibiotics. | LitMetric

AI Article Synopsis

  • - The bacterial cell wall peptidoglycan is crucial for maintaining cell shape and integrity against internal pressure, and its synthesis is a target for antibiotics like methicillin and vancomycin.
  • - The research focused on how antibiotics affect peptidoglycan synthesis and breakdown, revealing that while antibiotics can kill bacteria by promoting hydrolase activity that breaks down the wall, they can also cause stasis by blocking hydrolase actions when essential regulatory systems are depleted.
  • - The study shows that the balance between peptidoglycan synthesis and hydrolysis determines bacterial fate—allowing growth, causing death, or inducing stasis—which could inform new treatment strategies against bacterial infections.

Article Abstract

Bacterial cell wall peptidoglycan is essential, maintaining both cellular integrity and morphology, in the face of internal turgor pressure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of due to depletion of the essential, two-component and positive regulatory system for peptidoglycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicillin and vancomycin treatment lead to the appearance of perforating holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and misshapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bactericidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of peptidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For , the independent regulation of cell wall synthesis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612353PMC
http://dx.doi.org/10.1073/pnas.2106022118DOI Listing

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