The "comfort timing" strategy: a potential pathway for the cultivation of uncultured microorganisms and a possible adaptation for environmental colonisation.

Efforts to isolate uncultured microorganisms over the last century and a half, as well as the advanced 'omics' technologies developed over the last three decades, have greatly increased the knowledge and resources of microbiology. However, many cellular functions such as growth remain unknown in most of the microbial diversity identified through genomic sequences from environmental samples, as evidenced by the increasingly precise observations of the phenomenon known as the 'great plate count anomaly'. Faced with the many microbial cells recalcitrant to cultivation present in environmental samples, Epstein proposed the 'scout' model, characterised by a dominance of dormant cells whose awakening would be strictly stochastic. Unfortunately, this hypothesis leaves few exploitable possibilities for microbial cultivation. This review proposes that many microorganisms follow the 'comfort timing' strategy, characterised by an exit from dormancy responding to a set of environmental conditions close to optimal for growth. This 'comfort timing' strategy offers the possibility of designing culture processes that could isolate a larger proportion of uncultured microorganisms. Two methods are briefly proposed in this article. In addition, the advantages of dormancy, of the 'scout' model and of the 'comfort timing' strategy for survival under difficult conditions, but also for colonisation of environments, are discussed.