Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a.

Abstract

BACKGROUND:

A major complication of using medical devices is the development of biofilm-associated infection caused by Staphylococcus epidermidis where polysaccharide intercellular adhesin (PIA) is a major mechanism of biofilm accumulation. PIA affects innate and humoral immunity in isolated cells and animal models. Few studies have examined these effects in prosthetic joint infection (PJI).

METHODS:

This study used ex vivo whole blood modelling in controls together with matched-serum and staphylococcal isolates from patients with PJI.

RESULTS:

Whole blood killing of PIA positive S. epidermidis and its isogenic negative mutant was identical. Differences were unmasked in immunosuppressed whole blood pre-treated with dexamethasone where PIA positive bacteria showed a more resistant phenotype. PIA expression was identified in three unique patterns associated with bacteria and leukocytes, implicating a soluble form of PIA. Purified PIA reduced whole blood killing while increasing C5a levels. In clinically relevant staphylococcal isolates and serum samples from PJI patients; firstly complement C5a was increased 3-fold compared to controls; secondly, the C5a levels were significantly higher in serum from PJI patients whose isolates preferentially formed PIA-associated biofilms.

CONCLUSIONS:

These data demonstrate for the first time that the biological effects of PIA are mediated through C5a in patients with PJI.

• Authors: Rand Al-Ishaq, Jayne Armstrong, Martin Gregory, Miriam O'Hara, Kudzai Phiri, Llinos G Harris, Holger Rohde, Nicolaus Siemssen, Lars Frommelt, Dietrich Mack, Thomas S Wilkinson
• Journal: International journal of medical microbiology : IJMM (Int J Med Microbiol) Vol. 305 Issue 8 Pg. 948-56 (Dec 2015) ISSN: 1618-0607 [Electronic] Germany
• PMID: 26365169 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical References

• Polysaccharides, Bacterial
• polysaccharide intercellular adhesin
• Complement C5a

Topics

• Arthritis (microbiology)
• Blood Bactericidal Activity
• Complement C5a (metabolism)
• Host-Pathogen Interactions
• Humans
• Polysaccharides, Bacterial (metabolism)
• Prosthesis-Related Infections (microbiology)
• Staphylococcus epidermidis (growth & development, isolation & purification, metabolism, physiology)