JAC Advance Access published online on September 20, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf192
© 2002 by The British Society for Antimicrobial Chemotherapy
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Original Paper
1 University Department
of Bacteriology and Immunology, University of Glasgow, Royal Infirmary,
84-86 Castle Street, Glasgow G4 OSF, UK
* Corresponding author. E-mail: cgg1g{at}clinmed.gla.ac.uk.
Received 12 February 2002
; revised 7 June 2002
; accepted 23 July 2002
Linezolid is a new oxazolidinone with potent antibacterial
activity against Gram-positive cocci; it uniquely inhibits bacterial
translation through inhibition of 70S initiation complex formation. The
effects of sub-growth-inhibitory concentrations of linezolid on
the expression of various structural and soluble virulence factors
of Staphylococcus aureus and Streptococcus pyogenes were
examined. For S. aureus, strains Wood 46 and Cowan
1 (NCTC 8532) were used to measure protein A, coagulase,
Virulence factor expression by Gram-positive cocci
exposed to subinhibitory concentrations of linezolid
2 Pharmacia Corp., Kalamazoo, MI,
USA
-haemolysin
(hla) and 
-haemolysin (hld). For S. pyogenes, strain NCTC 9994 was used to measure
M protein, streptolysin O (SLO) and DNase. Coagulase was assayed
by clotting of citrated rabbit plasma, and hla, hld and SLO by lysis
of rabbit, human and horse erythrocytes, respectively. Protein A
and M protein were measured indirectly using bacterial susceptibility
to phagocytic ingestion of radiolabelled bacteria by human neutrophils. When S. aureus was grown in 1/2, 1/4 and 1/8 MIC, linezolid,
coagulase, hla and hld production were impaired. Susceptibility
to phagocytosis was changed by growth in the presence of 1/2 MIC linezolid
compared with that in its absence (50.8 ± 4.1% versus
38.9 ± 2.9%; P 
0.05). When
S. pyogenes was grown in 1/2, 1/4 and 1/8 MIC linezolid,
SLO and DNase production were impaired compared with that of bacteria
grown in the absence of the drug; its susceptibility to phagocytosis
was also increased (52.8% bacteria ingested versus 37.5%; P 0.05). A reduction in
virulence factor expression at sub-MIC linezolid concentrations
may be of benefit in the treatment of Gram-positive infections.
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