MEDUSA: Pathogen-Induced Chromatin Trapping and the PDK-PDH Metabolic Lock - A hypothesis of failed occasion-responsive chromatin transition

Post-infectious cellular dysfunction can persist after the acute pathogen encounter resolves.MEDUSA proposes one mechanism by which a pathogen-induced defensive chromatinarrangement could become difficult to replace. If that programme recruits pyruvatedehydrogenase kinase (PDK) strongly enough, inhibition of the pyruvate dehydrogenase complex (PDH) may constrain metabolic support required for the next chromatin transition. The existing PDK-permissive arrangement is already built, whereas its successor still requires metabolic work to construct. Retained accessibility can therefore continue replenishing short-lived PDK while PDH constraint obstructs replacement of the regulatory arrangement producing it. The cell remains alive, but regulatory availability becomes insufficiently dynamic for changing biological occasions. MEDUSA predicts persistent successor transcriptotypes, cell- and tissue-specific consequences, and recovery defined not by restoration of an old chromatin state but by restored capacity to change again. The individual biological relationships are independently testable; their coupling into this self-maintaining transition failure remains a hypothesis.