Reduction of the Peptidoglycan Crosslinking Causes a Decrease in Stiffness of the Staphylococcus aureus Cell Envelope

Loskill, Peter; Pereira, Pedro M.; Jung, Philipp; Bischoff, Markus; Herrmann, Mathias; Pinho, Mariana G.; Jacobs, Karin

doi:10.1016/j.bpj.2014.07.029

Cited by 81 publications

(86 citation statements)

References 53 publications

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“…Cross-linking in Lactococcus lactis involves the synthesis of an interpeptide bridge made of one D-amino acid (D-Asp or D-Asn), and in this species the PG cross-linking index was estimated to be 35.5% (2). Studies of Staphylococcus aureus have revealed that this PG cross-linking correlates with CW rigidity (3).…”

Section: Peptidoglycan (Pg)mentioning

confidence: 99%

Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis

Solopova

Formosa-Dague

Courtin

et al. 2016

Journal of Biological Chemistry

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To ensure optimal cell growth and separation and to adapt to environmental parameters, bacteria have to maintain a balance between cell wall (CW) rigidity and flexibility. This can be achieved by a concerted action of peptidoglycan (PG) hydrolases and PG-synthesizing/modifying enzymes. In a search for new regulatory mechanisms responsible for the maintenance of this equilibrium in Lactococcus lactis, we isolated mutants that are resistant to the PG hydrolase lysozyme. We found that 14% of the causative mutations were mapped in the guaA gene, the product of which is involved in purine metabolism. Genetic and transcriptional analyses combined with PG structure determination of the guaA mutant enabled us to reveal the pivotal role of the pyrB gene in the regulation of CW rigidity. Our results indicate that conversion of L-aspartate (L-Asp) to N-carbamoyl-L-aspartate by PyrB may reduce the amount of L-Asp available for PG synthesis and thus cause the appearance of Asp/Asn-less stem peptides in PG. Such stem peptides do not form PG cross-bridges, resulting in a decrease in PG cross-linking and, consequently, reduced PG thickness and rigidity. We hypothesize that the concurrent utilization of L-Asp for pyrimidine and PG synthesis may be part of the regulatory scheme, ensuring CW flexibility during exponential growth and rigidity in stationary phase. The fact that L-Asp availability is dependent on nucleotide metabolism, which is tightly regulated in accordance with the growth rate, provides L. lactis cells the means to ensure optimal CW plasticity without the need to control the expression of PG synthesis genes.Peptidoglycan (PG) 8 is the major component of the Grampositive bacterial cell wall (CW), which envelops the cell as a multilayer sacculus. PG consists of a basic unit made up of N-acetylglucosamine-N-acetylmuramic acid (GlcNAc-MurNAc) disaccharides bound to stem pentapeptides. Disaccharide pentapeptide units are synthesized intracellularly and transported through the cytoplasmic membrane as lipid-disaccharide pentapeptides called lipid II. These blocks are covalently linked to the pre-existing PG polymers by high molecular weight penicillin-binding proteins (PBPs) (1). Class A PBPs contain both transglycosylation and transpeptidation domains, whereas class B PBPs are involved only in transpeptidation. Transglycosylation links the disaccharide pentapeptide to the pre-existing PG chain, whereas transpeptidation connects the stem pentapeptides to neighboring chains, which ensures PG cross-linking through the formation of an interpeptide bridge. Cross-linking in Lactococcus lactis involves the synthesis of an interpeptide bridge made of one D-amino acid (D-Asp or D-Asn), and in this species the PG cross-linking index was estimated to be 35.5% (2). Studies of Staphylococcus aureus have revealed that this PG cross-linking correlates with CW rigidity (3).The basic PG structure is often modified as PG glycan chains can undergo N-deacetylation or O-acetylation, and free carboxyl groups of amino acids of peptide chains ...

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Section: Peptidoglycan (Pg)mentioning

confidence: 99%

Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis

Solopova

Formosa-Dague

Courtin

et al. 2016

Journal of Biological Chemistry

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“…Amongst others, Staphylococcus aureus has shown an increased likelihood to colonise and infect implants in humans and its presence is related to negative clinical prognosis [10][11][12] . Furthermore, in recent years S. aureus has demonstrated increased antibiotic resistance and as a result, novel antibacterial and anti-adhesive approaches are currently being explored in hopes of developing new strategies against biomaterial surface infection [13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Influence of biomaterial nanotopography on the adhesive and elastic properties of Staphylococcus aureus cells

et al. 2016

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Abstract:Despite the well-known beneficial effects of biomaterial nanopatterning on host tissue integration, the influence of controlled nanoscale topography on bacterial colonisation and infection remains unknown. Therefore, the aim of the present study was to determine the nanoscale effect of surface nanopatterning on biomaterial colonisation by S. aureus, utilising AFM nanomechanics and single-cell force spectroscopy (SCFS). Nanoindentation of S. aureus bound to planar (PL) and nanopatterned (SQ) polycarbonate (PC) surfaces suggested two distinct areas of mechanical properties, consistent with a central bacterial cell surrounded by a capsullar component. Nevertheless, no differences in elastic moduli were found between bacteria bound to PL and SQ, suggesting a minor role of nanopatterning in bacterial cell elasticity. Furthermore, SCFS demonstrated increased adhesion forces and work between S. aureus and SQ surfaces at 0s and 1s contact times. Although WLC modelling showed similarities in contour lengths for attachment to both surfaces, Poisson analysis suggests increased short-range forces for the S. aureus-SQ interactions. In the case of S. aureus-PL, long-range forces were found to not only be dominant but also repulsive in nature, which may help explain the reduced adhesion forces observed during AFM probing. In conclusion, although surface nanopatterning does not significantly influence the elasticity of attached bacterial cells, it was found to promote the early-adhesion of S. aureus cells to the biomaterial surface.

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“…As such, its composition and structure are linked to cell wall stiffness and susceptibility to binding partners, features that have important implications in drug resistance to cell wall antibiotics and host immunity. Recently, it has been demonstrated that changes to levels of cross-linking of the stem peptide chains by PBP TP correlate with methicillin resistance in Staphylococcus aureus (11). In another example, the replacement of the fifth-position D-alanine with D-lactic acid in the stem peptide of Enterococcus faecium and Enterococcus faecalis directly renders these pathogens resistant to the antibiotic vancomycin (12).…”

mentioning

confidence: 99%

d-Amino Acid Probes for Penicillin Binding Protein-based Bacterial Surface Labeling

Fura

Kearns

Pires

2015

Journal of Biological Chemistry

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Reduction of the Peptidoglycan Crosslinking Causes a Decrease in Stiffness of the Staphylococcus aureus Cell Envelope

Cited by 81 publications

References 53 publications

Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis

Regulation of Cell Wall Plasticity by Nucleotide Metabolism in Lactococcus lactis

Influence of biomaterial nanotopography on the adhesive and elastic properties of Staphylococcus aureus cells

d-Amino Acid Probes for Penicillin Binding Protein-based Bacterial Surface Labeling

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