JAC Advance Access originally published online on September 20, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 665-672
© 2002 The British Society for Antimicrobial Chemotherapy
Virulence factor expression by Gram-positive cocci exposed to subinhibitory concentrations of linezolid
1 University Department of Bacteriology and Immunology, University of Glasgow, Royal Infirmary, 84–86 Castle Street, Glasgow G4 OSF, UK; 2 Pharmacia Corp., Kalamazoo, MI, USA
Received 12 February 2002; returned 7 June 2002; revised 15 July 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, 
-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.
* Corresponding author. Tel: +44-141-211-4654; Fax: +44-141-552-1524; E-mail: cgg1g{at}clinmed.gla.ac.uk
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