e-space
Manchester Metropolitan University's Research Repository

The pentameric, but not the monomeric, isoform of C-reactive protein (CRP) enhances phagocytosis of methicillin-resistant Staphylococcus aureus (MRSA); potential implications for treatment strategies.

Hall, NR and Slevin, Mark and Gilmore, William and Ashworth, JJ (2017) The pentameric, but not the monomeric, isoform of C-reactive protein (CRP) enhances phagocytosis of methicillin-resistant Staphylococcus aureus (MRSA); potential implications for treatment strategies. In: Microbial Pathogenesis and Host Response, 12 September 2017 - 16 September 2017, Cold Spring Harbor Laboratory, New York. (Unpublished)

[img]
Preview

Download (34kB) | Preview

Abstract

Evidence indicates C-reactive protein (CRP) is not only a marker of infection but has a protective role, principally through the activation of complement and opsonisation of bacterial pathogens. However, of the two isoforms of CRP, native-CRP (nCRP) and monomeric-CRP (mCRP), it is unknown which isoform confers protection against bacterial infections. The aim of this study was to determine the effect CRP isoforms on macrophage-mediated clearance of methicillin-resistant Staphylococcus aureus (MRSA) in an in vitro phagocytosis assay using concentrations of mCRP (100µg/ml and 250µg/ml) or nCRP (500µg/ml and 1000µg/ml) that reflect acute human inflammatory responses. CRP-induced phagocytosis was explored further using wortmannin, SB203580 and PD98059 to inhibit phosphatidylinositol 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK) and MAPK/ extracellular signal-regulated kinase (MAPK/ERK) pathways respectively. Treatment with mCRP had no significant (P>0.05) effect on MRSA clearance compared to the untreated control, whereas nCRP significantly (P<0.01) increased phagocytosis of MRSA in a concentration-dependent manner. The nCRP-induced phagocytosis was significantly (P<0.01) reversed by inhibiting PI3K, p38 MAPK or MAPK/ERK (MEK). These findings suggest dissociation of nCRP to mCRP at sites of infection may lead to impaired bacterial clearance whereas local blockade of mCRP formation may be a viable therapeutic strategy for MRSA infections.

Impact and Reach

Statistics

Downloads
Activity Overview
7Downloads
123Hits

Additional statistics for this dataset are available via IRStats2.

Actions (login required)

Edit Item Edit Item