Are small colony variants responsible for chronic infections?

Researchers propose that during unfavorable conditions, especially antibiotic therapy, small colony variants (SCVs) are selected due to their ability to tolerate antibiotics. This is considered to be a survival strategy of bacteria to overcome adverse conditions. Upon the removal of unfavorable conditions, the SCVs revert to normal growth and cause re-infection. Moreover, they have enhanced capacity to persist intracellularly which may protect them from antibodies and complements. In many chronic infections, SCVs are isolated in large numbers. Isolation of SCVs from osteomyelitis and cystic fibrosis supports a pathogenic role for SCVs in such chronic diseases. In these cases, both large colonies and SCVs are isolated and researchers have shown that both colony types are clonal indicating a common origin. Thus, it is proposed that the normal large colonies are the revertants of SCVs.

Even though both the colony types might have originated from the common ancestor, however, there is no indication that the large colonies are truly the revertants of SCVs. In fact, there are no clear data that have proven the reversion of SCVs to large colony types in vivo. The isolation of both large and small colony types from such infections only indicates that, antibiotics are unable to kill all bacteria. Since some of the normal bacteria also survive, they may result in re-infection later. Thus, researchers have given undue importance to SCVs assuming that normal colonies are reverted from SCVs.

The fundamental flaw here- the assumption that antibiotics are capable of killing all normal bacteria under such chronic infections. (It is well established that antibiotics may not be able to kill all bacteria in biofilms or in other pathological conditions resulting in cystic fibrosis or chronic osteomyelitis). However, the reversion of SCVs to normal types in vitro made researchers to assume that the normal colonies found in vivo are also the revertants of SCVs.

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