Small colony variants of Staphylococci: a link to persistent infections

In prospective studies, Staphylococcus aureus small-colony variants (SCVs) have been linked to persistent and recurrent infections. SCVs are a naturally occurring subpopulation often defective in electron transport which may be identified in the microbiological laboratory as nonpigmented, nonhemolytic, slow-growing pinpoint colonies after incubation on rabbit blood agar. In addition, the often relatively unstable SCVs demonstrate a number of other characteristics that are atypical for S. aureus including reduced alpha-toxin production and delayed coagulase activity. A site-directed hemB mutant with a stable SCV phenotype provided strong evidence for the link between these electron transport defective strains and persistent infections. The hemB mutant was phagocytized by cultured endothelial cells, but did not lyse these cells, because the mutant produced very little alpha-toxin. Thus, SCVs can hide within the host cell, then revert to the highly virulent rapidly growing form and lyse the host cell, once the host immune response has abated and antibiotic therapy is completed. The intracellular position shields SCVs from host defenses and decreases exposure to antibiotics. This review discusses what is known of the biology of SCVs and describes the recovery and significance of Staphylococcus SCVs in clinical specimen.