Why are many archaea difficult to grow in laboratory cultures?

Many archaea are difficult to grow in laboratory settings because they are often extremophiles that require highly specific, harsh environmental conditions to survive and reproduce. These conditions—such as extreme temperatures, high salinity, high hydrostatic pressure, or specific anaerobic (oxygen-free) environments—can be challenging and costly to replicate in a standard laboratory pure culture.21

Furthermore, some archaea have complex biological requirements that are not yet fully understood. For instance, certain lineages, such as the Nanoarchaeota, are known to be obligate symbionts that must grow and divide on the surface of another host archaeon, making them impossible to isolate in pure culture. Because of these difficulties, the vast majority of archaea remain uncultivated. Scientists have instead realized their widespread presence and ecological importance through culture-independent techniques, such as analyzing DNA and RNA directly from environmental samples.2