The alarming rate at which pathogens are becoming resistant to conventional therapies
is a reason for the urgent need to develop alternative strategies to combat bacterial
infections. MGN-3 (biobran) was discovered and named after the three scientists:
Maeda, Ghoneum and Ninomiya. It is an enzymatically modified rice bran arabinoxylan,
which can enhance the host immune system by mediating macrophage function. The
aim of this study was to investigate the effect of MGN-3 on the clearance of methicillinresistant
Staphylococcus aureus (MRSA) by human U937 macrophages. The uptake of
MGN-3 by U937 macrophages was measured by a phloroglucinol colorimetric assay and
visualised by confocal microscopy. An in vitro host-pathogen assay (n=24) was
performed following exposure of macrophages to MGN-3 (0.5 to 2.0 mg/ml) and/or
lipopolysaccharide (LPS) at 1.0 μg/ml or 5.0 μg/ml for 24 hours. The assay was repeated
in the presence of receptor inhibitors, to identify potential molecular mechanisms of
action. Bacterial internalisation by U937 macrophages was visualised by scanning
electron microscopy (SEM).
The study demonstrated approximately 29% of total available MGN-3 was taken up by
U937 macrophages. There was a significant (P<0.05) dose-dependent increase in
clearance of MRSA by U937 macrophages in the presence of MGN-3 compared to the
negative control. SEM confirmed internalisation of MRSA by U937 macrophages
following MGN-3 treatment. However, MGN-3 inhibited LPS-induced phagocytosis,
suggesting both polysaccharides may compete as ligands for the same receptor(s) but
that LPS is more potent at inducing phagocytosis. TLR-4 and dectin-1 receptor inhibition
reversed the effects of MGN-3 or LPS treatment, suggesting both MGN-3 and LPS
mediate phagocytosis at least in part through these receptors.
In conclusion, this study established that MGN-3 significantly promotes phagocytosis of
MRSA by U937 macrophages in a dose-dependent manner via TLR-4 and dectin-1.
Moreover, MGN-3 mediated LPS-induced phagocytosis, suggesting competition for the
same receptor(s) and highlighting the potential of MGN-3 to modulate excessive LPSinduced
pro-inflammatory responses. Collectively, these findings may ultimately lead to
novel potential therapeutic strategies that can be used alongside antibiotic treatments
to combat MRSA infection, thereby reducing the over reliance on antibiotic usage
