The small colony variant (SCV) concept -- the role of staphylococcal SCVs in persistent infections.
The recovery of small colony variants (SCVs) from clinical specimens was first described at the beginning of the last century. However, not until the past decade was an association of these variants with chronic, recurrent, and persistent infections such as chronic osteomyelitis and persistent skin and softtissue infection described. Since then, a number of reports and prospective studies have supported a pathogenic role for SCVs in disease. Biochemical and other characteristics of SCVs have suggested a link between electron-transport defective SCV strains and persistent infections, however, the strains examined were genetically undefined SCVs. Therefore, a stable mutant in electron transport was generated by interrupting one of the hemin biosynthetic genes, hemB, in Staphylococcus aureus. This mutant showed characteristics typical of clinical SCVs such as slow growth, decreased pigment formation, low coagulase activity, reduced hemolytic activity, and resistance to aminoglycosides. Furthermore, the mutant was able to persist within cultured endothelial cells due to decreased a-toxin production. It was suggested that the intracellular location of this subpopulation might shield the variants from host defenses and antibiotics, thus providing one explanation for the difficulty in removing SCVs from host tissues. Therefore, a defect in the electron-transport system allows S. aureus SCVs to resist aminoglycosides and persist intracellularly. Because of their fastidious growth characteristics, they are easily missed or misidentified in the clinical laboratory. Therefore, when an infection persists for weeks or months or fails to respond to antimicrobial therapy, clinicians as well as laboratory personnel should consider further efforts to search for this staphylococcal subpopulation.
von Eiff
Christof
C
Institut für Medizinische Mikrobiologie, Universitätsklinikum Münster, Münster, Germany. eiffc@uni-muenster.de
Peters
Georg
G
Becker
Karsten
K
D000818:Animals; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation; D010019:Osteomyelitis / Q000382:microbiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*