The small colony variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild type (WT) S. aureus strain and its counterpart SCV phenotype both in vitro and in vivo, using the THP-1 cell line model and mouse peritonitis model respectively. Both phenotypes infected the mouse peritoneum intra- and extracellularly. The SCV phenotype was less virulent, showed distinct bacterial clearance, reduced multiplication capacity and reduced internalization ability. Some of the SCV infected mice were, however, still culture positive up to 96 h post infection and the phenotype could spread to the mouse kidney and furthermore revert to the more virulent WT phenotype in both the mouse- peritoneum and kidney. The SCV phenotype is therefore, despite reduced virulence, an important player in the S. aureus pathogenesis. In the THP-1 cell line model, both dicloxacillin (DCX) and linezolid (LZD) reduced the intracellular inoculum of both phenotypes by approximately 1-1.5 log10 in vitro, while DCX was considerably more effective against extracellular bacteria. In the mouse peritonitis model, DCX and LZD were also able to control both the intra- and extracellular infection caused by either phenotype. Treatment with a single dose of DCX and LZD was, however, insufficient to clear the SCVs in the kidneys and the risk of recurrent infection remained. This stresses the importance of optimal dosing of the antibiotic when SCVs are present.
2011. Vol. 55, no 4, 1443-1452 p.