If ATP and macromolecular synthesis are needed for dormant spores of Bacillota species to trigger spore germination, where do the energy and precursors come from?

ATP is one of the signature molecules of life. As the primary energy currency of cells, the debate concerning its involvement, if any, in driving the earliest biophysical events associated with germination of dormant Bacillota spores has continued without resolution for several decades. With a view to framing the debate, this article presents a synopsis of fundamental aspects of spore physiology coupled with key experimental observations in the context of bioenergetics and macromolecular synthesis. Evidently, neither the spore core nor the inner membrane present sub-cellular environments conducive to significant oxidative- or substrate-level phosphorylation, gene transcription, or protein translation activities. Additionally, neither the precursors of numerous critical macromolecules, nor the cellular apparatus required to synthesize these precursors, are present in dormant spores. Even if these might somehow be generated within localized micro-environments, the phosphorylation potential associated with the negligible quantities of ATP present in spores is severely reduced relative to actively metabolizing cells as a result of spores' sub-optimal adenylate energy charge. Thus, the scope for significant macromolecular synthesis is thermodynamically improbable. Looking ahead, clarity in the field of spore bioenergetics and metabolism will only be achieved by studies that unambiguously encompass the physiological constraints imposed by these most resolute cells.