title: Reduction of the peptidoglycan crosslinking causes a decrease in stiffness of the Staphylococcus aureus cell envelope.
abstract: We have used atomic-force microscopy (AFM) to probe the effect of peptidoglycan crosslinking reduction on the elasticity of the Staphylococcus aureus cell wall, which is of particular interest as a target for antimicrobial chemotherapy. Penicillin-binding protein 4 (PBP4) is a nonessential transpeptidase, required for the high levels of peptidoglycan crosslinking characteristic of S. aureus. Importantly, this protein is essential for β-lactam resistance in community-acquired, methicillin-resistant S. aureus (MRSA) strains but not in hospital-acquired MRSA strains. Using AFM in a new mode for recording force/distance curves, we observed that the absence of PBP4, and the concomitant reduction of the peptidoglycan crosslinking, resulted in a reduction in stiffness of the S. aureus cell wall. Importantly, the reduction in cell wall stiffness in the absence of PBP4 was observed both in community-acquired and hospital-acquired MRSA strains, indicating that high levels of peptidoglycan crosslinking modulate the overall structure and mechanical properties of the S. aureus cell envelope in both types of clinically relevant strains. Additionally, we were able to show that the applied method enables the separation of cell wall properties and turgor pressure.
authors.affiliation: Experimental Physics, Saarland University, Saarbrücken, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Loskill
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Pereira
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jung
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal. Electronic address: mgpinho@itqb.unl.pt.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Pinho
authors.affiliation: Experimental Physics, Saarland University, Saarbrücken, Germany. Electronic address: k.jacobs@physik.uni-saarland.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Jacobs
mesh_terms: D002473:Cell Wall / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D055119:Elastic Modulus; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D046915:Penicillin-Binding Proteins / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000737:chemistry*
chemical_list: D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan