Proton-Binding Capacity of Staphylococcus aureus Wall Teichoic Acid and Its Role in Controlling Autolysin Activity

PLOS ONE, Dec 2019

Wall teichoic acid (WTA) or related polyanionic cell wall glycopolymers are produced by most Gram-positive bacterial species and have been implicated in various cellular functions. WTA and the proton gradient across bacterial membranes are known to control the activity of autolysins but the molecular details of these interactions are poorly understood. We demonstrate that WTA contributes substantially to the proton-binding capacity of Staphylococcus aureus cell walls and controls autolysis largely via the major autolysin AtlA whose activity is known to decline at acidic pH values. Compounds that increase or decrease the activity of the respiratory chain, a main source of protons in the cell wall, modulated autolysis rates in WTA-producing cells but did not affect the augmented autolytic activity observed in a WTA-deficient mutant. We propose that WTA represents a cation-exchanger like mesh in the Gram-positive cell envelopes that is required for creating a locally acidified milieu to govern the pH-dependent activity of autolysins.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0041415&type=printable

Proton-Binding Capacity of Staphylococcus aureus Wall Teichoic Acid and Its Role in Controlling Autolysin Activity

et al. (2012) Proton-Binding Capacity of Staphylococcus aureus Wall Teichoic Acid and Its Role in Controlling Autolysin Activity. PLoS ONE 7(7): e41415. doi:10.1371/journal.pone.0041415 Proton-Binding Capacity of Staphylococcus aureus Wall Teichoic Acid and Its Role in Controlling Autolysin Activity Raja Biswas 0 Raul E. Martinez 0 Nadine Go hring 0 Martin Schlag 0 Michaele Josten 0 Guoqing Xia 0 Florian Hegler 0 Cordula Gekeler 0 Anne-Kathrin Gleske 0 Friedrich Go tz 0 Hans-Georg Sahl 0 Andreas Kappler 0 Andreas Peschel 0 Vance G. Fowler, Duke University Medical Center, United States of America 0 1 Interfaculty Institute of Microbiology and Infection Medicine , Cellular and Molecular Microbiology , University of Tu bingen , Tu bingen, Germany, 2 Center for Applied Geoscience, Geomicrobiology , University of Tu bingen , Tu bingen, Germany , 3 Interfaculty Institute of Microbiology and Infection Medicine , Microbial Genetics , University of Tu bingen , Tu bingen, Germany , 4 Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn , Bonn , Germany Wall teichoic acid (WTA) or related polyanionic cell wall glycopolymers are produced by most Gram-positive bacterial species and have been implicated in various cellular functions. WTA and the proton gradient across bacterial membranes are known to control the activity of autolysins but the molecular details of these interactions are poorly understood. We demonstrate that WTA contributes substantially to the proton-binding capacity of Staphylococcus aureus cell walls and controls autolysis largely via the major autolysin AtlA whose activity is known to decline at acidic pH values. Compounds that increase or decrease the activity of the respiratory chain, a main source of protons in the cell wall, modulated autolysis rates in WTA-producing cells but did not affect the augmented autolytic activity observed in a WTA-deficient mutant. We propose that WTA represents a cation-exchanger like mesh in the Gram-positive cell envelopes that is required for creating a locally acidified milieu to govern the pH-dependent activity of autolysins. - Funding: This work was supported by the German Research Foundation grants TRR34 to A.P. and F.G. and SFB766 to A.P., G.X., and F.G.; by the Bacteria Materials Interaction graduate programme of the University of Tu bingen to A.P. and A.K.; and by a fellowship from the Humboldt Foundation to R.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. The bacterial cell envelope governs vital processes including maintenance of cell shape, cell division, and protection against environmental challenges. In addition, it has a crucial role in the respiratory energy metabolism because the cytoplasmic membrane harbors the electron transport chain components, which generate a proton gradient across the membrane that is used to generate ATP or energize transport processes [1,2]. The majority of Gram-positive bacteria contain polyanionic cell wall glycopolymers (CWGs) in their cell envelopes, which are covalently linked to either peptidoglycan (e.g. wall teichoic acid [WTA] or teichuronic acid) or membrane glycolipids (e.g. lipoteichoic acid [LTA] or succinylated lipoglycans) [3]. Several roles in the protection and maintenance of Gram-positive cell envelopes and in bacteria-host interaction have been assigned to CWGs after WTA or LTA-deficient mutants became available in Staphylococcus aureus and Bacillus subtilis [46]. Moreover, the cell envelope of B. subtilis cells has been shown to be protonated during respiratory metabolism [7,8] and the polyanionic CWGs have been implicated in cation binding [9,10]. However, it has remained unclear if the proton-binding capacity of WTA may impact on the pH-sensitive activity of cell wall-associated enzymes such as autolysins. Peptidoglycan is built from long glycan strands that are crosslinked by peptide side chains. Peptidoglycan must be continuously synthesized to maintain cell integrity and viability and to allow for cell division. Peptidoglycan hydrolytic autolysins are critical for separating daughter cells after cell division [11,12]. The maintenance of the peptidoglycan network requires a fine-tuned spatial and temporal control of autolysins to prevent suicidal cell death [13]. Yet, surprisingly little is known about the control of autolysins and the underlying regulatory principles are only superficially understood. Inactivation of AtlA, the major autolysin in S. aureus, or of the corresponding AtlE of Staphylococcus epidermidis is not lethal but the mutants form huge cell clusters as a result of incomplete cell separation [14]. While studying the role AtlA in S. aureus we observed that a WTA-deficient DtagO mutant (DtagO) [15] is much more susceptible to autolysis tha (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0041415&type=printable

Raja Biswas, Raul E. Martinez, Nadine Göhring, Martin Schlag, Michaele Josten, Guoqing Xia, Florian Hegler, Cordula Gekeler, Anne-Kathrin Gleske, Friedrich Götz, Hans-Georg Sahl, Andreas Kappler, Andreas Peschel. Proton-Binding Capacity of Staphylococcus aureus Wall Teichoic Acid and Its Role in Controlling Autolysin Activity, PLOS ONE, 2012, Volume 7, Issue 7, DOI: 10.1371/journal.pone.0041415