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Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus

Nature Reviews Microbiology volume 12, pages 49–62 (2014)Cite this article

Subjects

Key Points

  • Staphylococcus aureus is a commensal bacterium that can cause both superficial and invasive, potentially life-threatening, infections such as sepsis, endocarditis and pneumonia.

  • S. aureus can express a range of virulence factors, which include surface proteins that are covalently attached to peptidoglycan, known as cell wall-anchored (CWA) proteins.

  • On the basis of structural and functional data, CWA proteins can be grouped into four families: microbial surface component recognizing adhesive matrix molecule (MSCRAMM), near iron transporter (NEAT), three-helical bundle and G5–E repeat proteins.

  • MSCRAMM proteins, which are characterized by at least two adjacent IgG-folded domains in their amino-terminal A region, are the largest family. MSCRAMM proteins can bind to their ligands by a mechanism known as 'dock, lock and latch', or in a variation of this process, known as the 'collagen hug'.

  • S. aureus CWA proteins are important virulence factors that mediate iron acquisition, adhesion, biofilm formation, invasion, inflammation and evasion of innate and adaptive immunity. CWA proteins can be both multifunctional and functionally redundant.

  • CWA protein variation might have a role in defining the virulence of clinical isolates — for example, by increasing adhesion to biomaterial surfaces and indwelling medical devices. Furthermore, recombinant CWA proteins are potential vaccine candidates.

Abstract

Staphylococcus aureus is an important opportunistic pathogen and persistently colonizes about 20% of the human population. Its surface is 'decorated' with proteins that are covalently anchored to the cell wall peptidoglycan. Structural and functional analysis has identified four distinct classes of surface proteins, of which microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) are the largest class. These surface proteins have numerous functions, including adhesion to and invasion of host cells and tissues, evasion of immune responses and biofilm formation. Thus, cell wall-anchored proteins are essential virulence factors for the survival of S. aureus in the commensal state and during invasive infections, and targeting them with vaccines could combat S. aureus infections.

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Figure 1: Functions of CWA proteins of S. aureus.
Figure 2: Classification of CWA proteins on the basis of structural motifs.
Figure 3: Mechanisms of ligand binding by MSCRAMM proteins.
Figure 4: Roles of CWA proteins in biofilm formation.

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Acknowledgements

T.J.F. would like to acknowledge Science Foundation Ireland Programme Investigator grant 08/IN1/B1845. M.H. would like to acknowledge NIH grant AI 20624. The authors would like to thank D. Ravirajan for help with the on-line movie.

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Authors and Affiliations

  1. Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin, 2, Ireland

    Timothy J. Foster & Joan A. Geoghegan

  2. Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A & M University Health Science Center, Houston, 77030, Texas, USA

    Vannakambadi K. Ganesh & Magnus Höök

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  1. Timothy J. Foster
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  2. Joan A. Geoghegan
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  3. Vannakambadi K. Ganesh
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  4. Magnus Höök
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Correspondence to Timothy J. Foster.

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Glossary

Coagulase-negative staphylococci

Staphylococcus spp. (other than Staphylococcus aureus) that do not express coagulase and are less virulent.

Extracellular matrix

The extracellular components of tissue that often provide structural support for cells.

Fibronectin

A high-molecular-weight dimeric glycoprotein that is found in serum and in the extracellular matrix (ECM). It binds to integrins and to other components of the ECM.

Oxidative burst

A respiratory burst that is produced by phagocytic cells. NADPH oxidase causes the rapid release of reactive oxygen species (superoxide and hydrogen peroxide).

Complement

Proteins in serum that are activated by the presence of foreign antigens; a proteolytic cascade leads to the formation of the neutrophil opsosin C3b and the chemoattractant peptides C3a and C5a.

Apo form

The form of a protein without bound ligand.

Elastin

An elastic protein in connective tissue. It allows tissue to regain shape by stretching or contracting.

Isogenic

A term used to describe strains that are characterized by identical genes.

Squamous epithelium

The most superficial layer of stratified epithelium; it consists of flat, scale-like squamous epithelial cells (known as squames) that have a cornified envelope composed of proteins.

Ω loops

Strings of glycine and serine residues in keratin 10 and loricrin, flanked by hydrophobic amino acids. Modelling suggests the formation of structures that are shaped like the Greek capital letter Ω.

Fc regions

Fragment crystallizable regions at the tail of antibodies; they react with specific receptors on neutrophils and with the complement protein C1q to trigger the classical pathway of complement fixation.

Classical pathway

One of three pathways for activating complement fixation. Requires clustered IgG molecules with their Fc regions pointing outwards to attract the hexameric complement protein C1q.

Opsonin

A protein (antibody or complement protein) that enhances phagocytosis by neutrophils.

α-toxin

A β-barrel pore-forming cytolysin that is secreted as a monomer and forms a heptamer in the membranes of susceptible cells; it is an important virulence factor.

Tight junctions

Areas of close contact between the membranes of epithelial and endothelial cells; they are connected to the actin cytoskeleton.

Phage-display technology

Bacteriophages that display libraries of peptides that are incorporated into capsid proteins. Individual particles that bind to ligands are enriched by 'panning'. The peptide sequences are identified by DNA sequencing.

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Foster, T., Geoghegan, J., Ganesh, V. et al. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 12, 49–62 (2014). https://doi.org/10.1038/nrmicro3161

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