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

TY - JOUR

T1 - 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

AU - Al-Ishaq, Rand

AU - Armstrong, Jayne

AU - Gregory, Martin

AU - O'Hara, Miriam

AU - Phiri, Kudzai

AU - Harris, Llinos G

AU - Rohde, Holger

AU - Siemssen, Nicolaus

AU - Frommelt, Lars

AU - Mack, Dietrich

AU - Wilkinson, Thomas S

N1 - Copyright © 2015 Elsevier GmbH. All rights reserved.

PY - 2015/12

Y1 - 2015/12

N2 - 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.

AB - 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.

U2 - 10.1016/j.ijmm.2015.08.005

DO - 10.1016/j.ijmm.2015.08.005

M3 - SCORING: Journal article

C2 - 26365169

VL - 305

SP - 948

EP - 956

JO - INT J MED MICROBIOL

JF - INT J MED MICROBIOL

SN - 1438-4221

IS - 8

ER -