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Immune evasion by staphylococci

Key Points

  • The first line of defence against Staphylococcus aureus is neutrophil phagocytosis. The bacterium thwarts neutrophils by several novel mechanisms. A capsule and surface protein reduce opsonization. Secreted proteins prevent complement activation and inhibit neutrophil chemotaxis and migration. There are several mechanisms to resist killing by reactive oxygen species and antibacterial defensin peptides.

  • Transcriptional microarray studies identified many genes that are differentially regulated after neutrophil uptake. Community-acquired meticillin-resistant S. aureus strains are more virulent, have increased resistance to neutrophils and a larger repertoire of differentially regulated genes.

  • Secreted and wall-associated superantigens stimulate proliferation of T cells and B cells and interfere with normal antibody responses, causing immunosuppression. Immunization with purified surface polysaccharide and protein stimulates protective immunity, offering the prospect of vaccines to protect against infections.

  • Staphylococcus epidermidis lacks the diverse mechanisms of avoiding immunity. It relies on surface polymers to resist neutrophil phagocytosis.

Abstract

Staphylococcus aureus can cause superficial skin infections and, occasionally, deep-seated infections that entail spread through the blood stream. The organism expresses several factors that compromise the effectiveness of neutrophils and macrophages, the first line of defence against infection. S. aureus secretes proteins that inhibit complement activation and neutrophil chemotaxis or that lyse neutrophils, neutralizes antimicrobial defensin peptides, and its cell surface is modified to reduce their effectiveness. The organism can survive in phagosomes, express polysaccharides and proteins that inhibit opsonization by antibody and complement, and its cell wall is resistant to lysozyme. Furthermore, S. aureus expresses several types of superantigen that corrupt the normal humoral immune response, resulting in anergy and immunosuppression. In contrast, Staphylococcus epidermidis must rely primarily on cell-surface polymers and the ability to form a biolfilm to survive in the host.

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Figure 1: Pathways for complement activation.
Figure 2: Inhibition of the neutrophil response to infection.
Figure 3: Mechanisms by which Staphylococcus aureus avoids opsonophagocytosis.
Figure 4: Mechanisms of immunosuppression mediated by Staphylococcus aureus.

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Acknowledgements

I would like to thank the Science Foundation Ireland, the Health Research Board, the Wellcome Trust, the European Commission Framework 5 and Inhibitex Inc. for funding.

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DATABASES

Entrez

Bacillus anthracis

Pseudomonas aeruginosa

Staphylococcus aureus

Staphylococcus epidermis

Streptococcus pyogenes

Swiss-Prot

Aap

aureolysin

AtlE

C5aR

CHIPS

ClfA

ClfB

Cna

Efb

exotoxin A

Fbe

FPR

ICAM-1

lactoferrin

LFA-1

lysozyme

MrpF

protein A

PVL

SarA

SdrG

staphylokinase

TSST-1

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Foster, T. Immune evasion by staphylococci. Nat Rev Microbiol 3, 948–958 (2005). https://doi.org/10.1038/nrmicro1289

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