STAPHYLOCOCCUS-AUREUS SMALL COLONY VARIANTS CAUSE PERSISTENT AND RESISTANT INFECTIONS

Staphylococcus aureus small colony variants (SCVs) have been found to cause persistent and antibiotic-resistant infections in humans. Persis tence seems to relate to the ability of SCVs to reside within host cel ls without lysing them. The lytic activity of S. aureus arises from th e production of a-toxin, and SCVs are non-a-toxin-producing. The bioch emical basis for the SCV phenotype has been linked to decreased electr on transport which leads to reduced a-toxin production. Electron trans port is diminished due to blocks in either haemin or menadione biosynt hesis, which results in the loss of the menaquinone or cytochrome comp onents of the electron transport chain, respectively. Reduction in ele ctron transport activity also causes reduced coagulase production, dec reased pigmentation, and reduced aminoglycoside uptake. The decreased uptake of aminoglycosides comes from the weaker electrochemical gradie nt across the cell membrane. The SCVs are not only more resistant to t he positively charged aminoglycosides, but they are also resistant to several other positively charged antistaphylococcal compounds: protami ne, some L-antibiotics, and platelet microbicidal proteins. The multip le phenotypic changes, such as decreased haemolytic activity (a-toxin) , decreased coagulase activity, reduced pigmentation, and slow growth, make the SCVs difficult to recognize as S. aureus. Finally, the intra cellular milieu of the mammalian cell enhances the production of SCVs. Of interest, a number of other genera (both Gram-positive and Gram-ne gative) also produce electron transport SCVs that are resistant to ami noglycosides, hence the observations with S. aureus may apply to other types of organisms. Thus, the SCV phenotype allows S. aureus to persi st within host cells and resist antimicrobial agents, and the atypical colonial morphology may lead to misidentification of these organisms. Because many of the SCVs are menadione auxotrophs, the addition of vi tamin EC to the medium increases the activity of antibiotics against t hese variants which might prove to be a valuable therapeutic adjunct.