Demonstration of the role of cell wall homeostasis in <i>Staphylococcus aureus</i> growth and the action of bactericidal antibiotics
Bartłomiej Salamaga, Ling‐Yuan Kong, Laia Pasquina-Lemonche, Lucía Lafage, Milena L. von und zur Muhlen, Josie F. Gibson, Danyil Grybchuk, Amy K. Tooke, Viralkumar V. Panchal, Elizabeth Culp, Elizabeth Tatham, Mary E. O’Kane, Thomas E. Catley, Stephen A. Renshaw, Gerard D. Wright, Pavel Plevka, Per A. Bullough, Aidong Han, Jamie K. Hobbs, Simon J. Foster
Abstract
Significance The bacterial cell wall peptidoglycan is essential for maintenance of viability and yet is dynamic, permitting growth and division. Peptidoglycan synthesis is inhibited by important antibiotics, including β-lactams and vancomycin. Using the human pathogen Staphylococcus aureus , we have examined peptidoglycan homeostatic mechanisms and how their interruption leads to cell death. This has revealed two antibiotic-induced killing mechanisms mediated by specific peptidoglycan hydrolases, both involving the appearance of holes that span the entire thickness of the cell wall. One of the mechanisms is associated with growth and the other with cell division. This study supports a simple model for how cells grow via a combination of peptidoglycan synthesis and hydrolysis and how antibiotic intervention leads to cell death.