Article

Immune evasion by Staphylococci

Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
Nature Reviews Microbiology (Impact Factor: 23.32). 01/2006; 3(12):948-58. DOI: 10.1038/nrmicro1289
Source: PubMed

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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    • "SA can evade innate immunity by resisting phagocytosis and can survive inside neutrophils (Foster, 2005). SA can also evade induced immunity since SA can deplete potential antibody-secreting B cells and inhibit proliferation of antigen-specific T cells (Foster, 2005). GPA patients have an abnormal epithelial nasal barrier with an altered basal cytokine expression and a reduced secretion of interleukin-8 upon SA stimulation that could facilitate nasal carriage (Wohlers et al., 2012). "
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    ABSTRACT: Objective. Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods. Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75% of nasal swabs. Results. SA nasal carriage did not change during RTX (p = 0.297). However, the rate of positive nasal swabs in GPA patients with transient SA nasal carriage during RTX maintenance increased from 0 prior RTX to 0.42 during RTX (p = 0.017). Persistent SA nasal carriage did not increase the risk of relapses (p = 0.844), of hypogammaglobulinemia (p = 0.122) and of severe infections (p = 0.144), but reduced the risk of chronic infections (p = 0.044). Change in SA carriage status during RTX did not influence the risk of relapses (p = 0.756), hypogammaglobulinamia (p = 0.474) and infections, either severe (p = 0.913) or chronic (p = 0.121). Conclusion. Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not seem to increase the risk of relapses, but seemed to decrease the risk of hypogammaglobulinemia associated chronic infections.
    PeerJ 06/2015; 3(suppl. 57):e1051. DOI:10.7717/peerj.1051 · 2.10 Impact Factor
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    • "S. aureus has at its disposal several virulence factors, among them, surface proteins carry out an essential role in colonization and infection of the host. Indeed, surface proteins are involved in both adhesion to different structures of the host (cells and extracellular matrix) and immune defenses evasion (Foster et al., 2014; Rooijakkers et al., 2005; Speziale et al., 2009; Zecconi and Scali, 2013). Four different families of S. aureus surface proteins can be identified on a chemical structure basis. "
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    ABSTRACT: Staphylococcus aureus represents one of the leading causes of mastitis in dairy cows worldwide. S. aureus IMI have variable outcomes due to virulence of the strain involved, immune defenses of the host, and by antibiotic resistance. The difficulty in eradication and the increasing concerns on antibiotics usages underscore the interest in developing new tools to control S. aureus mastitis. Vaccination represents one of the most studied of these tools but, so far, no vaccine seems to provide reliable protection. This review summarizes current knowledge on the major vaccine targets, including surface proteins, capsular polysaccharides, biofilm, and toxins. Finally, the present status of vaccination against S. aureus and the future of vaccine design were discussed, including how differences among in vivo models may influence vaccines development. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Research in Veterinary Science 03/2015; 100. DOI:10.1016/j.rvsc.2015.03.019 · 1.51 Impact Factor
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    • "response to facilitate survival and establish infection. Anchored to the cell surface, Spa binds IgG Fc fragments, blocks their recognition by Fc receptors on neutrophils, and thereby prevents phagocytosis and classical pathway complement fixation (Atkins et al., 2008; Foster, 2005). Whether mutations within the repeat region of spa might explain the increased transcription rate of spa is not known. "
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    ABSTRACT: The lungs of Cystic fibrosis (CF) patients are often colonized and/or infected by Staphylococcus aureus for years, mostly by one predominant clone. For long-term survival in this environment, S. aureus needs to adapt during its interactions with host factors, antibiotics, and other pathogens. Here, we study long-term transcriptional as well as genomic adaptations of an isogenic pair of S. aureus isolates from a single patient using RNA sequencing (RNA-Seq) and whole genome sequencing (WGS). Mimicking in vivo conditions, we cultivated the S. aureus isolates using artificial sputum medium before harvesting RNA for subsequent analysis. We confirmed our RNA-Seq data using quantitative real-time (qRT)-PCR and additionally investigated intermediate isolates from the same patient representing in total 13.2 years of persistence in the CF airways. Comparative RNA-Seq analysis of the first and the last (“late”) isolate revealed significant differences in the late isolate after 13.2 years of persistence. Of the 2,545 genes expressed in both isolates that were cultivated aerobically, 256 genes were up- and 161 were down-regulated with a minimum 2-fold change (2f). Focusing on 25 highly (≥ 8f) up- (n = 9) or down- (n = 16) regulated genes, we identified several genes encoding for virulence factors involved in immune evasion, bacterial spread or secretion (e. g. spa, sak, and esxA). Moreover, these genes displayed similar expression trends under aerobic, microaerophilic and anaerobic conditions. Further qRT-PCR-experiments of highly up- or down-regulated genes within intermediate S. aureus isolates resulted in different gene expression patterns over the years. Using sequencing analysis of the differently expressed genes and their upstream regions in the late S. aureus isolate resulted in only few genomic alterations. Comparative transcriptomic analysis revealed adaptive changes affecting mainly genes involved in host-pathogen interaction. Although the underlying mechanisms were not known, our results suggest adaptive processes beyond genomic mutations triggered by local factors rather than by activation of global regulators.
    International Journal of Medical Microbiology 10/2014; 305(1). DOI:10.1016/j.ijmm.2014.10.005 · 3.42 Impact Factor
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