Intracellular persistence of small colony variants

It has been suggested that small colony variants (SCVs) can persist intracellularly and are protected against antibiotics and host innate defense system which may contribute to chronic infections (von Eiff et al. 2001). They may produce low levels of alpha-toxins which may help in the intracellular persistence by preventing cell lysis or apoptosis.

Tuchscherr et al. (2010) investigated the infection of endothelial cells with highly virulent wild type isolates and isogenic SCVs of S. aureus. They found that wild type bacteria upregulated the expression of a number of endothelial genes and proteins whereas SCVs upregulated only a few of them. Similarly, the levels of chemokine release after 3 days of infection was much higher with wild type cells when compared to SCVs. The data from the above article indicates that SCVs are less virulent when compared to wild type. They may be better in avoiding the host innate defense system and hence may persist inside the cells. Since they divide slowly, they may produce fewer products that activate host cell responses.

However, whether SCVs are adapted phenotypes that can cause chronic infections is unproven. In fact, previous experiments with animal models have also shown that SCVs are less virulent than their wild type counterparts. But whether they can occasionally give rise to normal wild type bacteria through in vivo reversion has not been demonstrated even though such reversion has been shown in vitro.

von Eiff et al. (2001). Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with darier's disease. Clin Infect Dis 32(11), 1643-7.

Tuchscherr et al. (2010). Staphylococcus aureus small colony variants are adapted phenotypes for intracellular persistence. Journal of Infectious Diseases 202(7): 1031-1040