Persisters, Biofilms, and the Problem of Cultivability

Abstract

The majority of bacterial species in the environment remain uncultured, and accumulating evidence suggests that this cannot be explained by inadequate nutrient supply. Good recovery of environmental bacteria can be obtained by cultivation in situ in diffusion chambers, and this produces “domesticated” variants that can subsequently grow on synthetic media on Petri dishes. In many cases, growth of otherwise unculturable bacteria is observed on rich media in the presence of a cultivable helper organism. In the marine sediment environment, a considerable part of these uncultivable bacteria are found to depend on siderophores produced by their neighbors. The absence of an ability to induce the synthesis of their own siderophores when iron levels drop is puzzling. It seems that these observations point to a signaling mechanism for uncultivability – most bacterial species evolved to grow only in a familiar environment. The default mode of most bacterial life is then dormancy, and growth factors are required for resuscitation. The adaptive advantage of such a strategy may stem from the fact that rapidly propagating bacteria are highly vulnerable to toxic factors such as unfamiliar antibiotics. By contrast, dormant cells are tolerant to antibiotics. This is exemplified by specialized dormant persister cells which are formed in all studied cultivable bacteria. In organisms such as E. coli or P. aeruginosa, persisters are formed stochastically and make up a small part of the population. It is possible that in the absence of a growth factor, unculturable species enter en mass into a persister state.