Becoming Archaea: Septic Shock, Warburg effect and loss of endosymbiotic relation-Billion year war of two genomes

Becoming Archaea: Septic Shock, Warburg effect and loss of endosymbiotic relation-Billion year war of two genomes.ABSTRACT : Septic shock is a major problem in medicine and carries high mortality rate. Irrespective of the advances in this field the underlying mechanism behind septic shock still remains a mystery. To understand septic shock we need to understand the evolution of eukaryotic cell and the billion year war between archaeal/nuclear genome and the bacterial/mitochondrial genome. The ancient infection of archaeal host by the bacteria (α-proteobacteria) resulted in the formation of eukaryotes and mitochondrial endosymbiont occurred >1.5 billion years ago and this extraordinary event is occurring from then on all the time till now resulted in formation of complex life forms. In this article I propose ‘Warburg common pathogenesis evolutionary model’, which has the potential to explain septic shock and most of the pathophysiological processes. I hypothesize that the bacterial/mitochondrial invasion of the eukaryote cell is supported by the mitochondrial system of the host eukaryotic cell and resisted by the innate immune system which is the archaeal part of the host eukaryotic cell, as archaea is the real host before it became eukaryote.Three major outcomes may result because of the bacterial /mitochondrial invasion related event,1) PAMP/DAMP via PRR eg.TLR4 over activates innate immune system which in turn inhibits the mitochondrial respiration and decreases the mitochondrial genome. Nuclear genome overpowers mitochondrial genome which results in the loss of the endosymbiotic relation between them, produces Warburg effect and the bacterial /mitochondrial invasion is successfully defeated. By Warburg effect, the eukaryotic host cell now returned to its original billion year old primitive form i.e. it became archaea like. This dedifferentiated state switching can be seen as the cells local survival strategy in response to injuries as the cells are now archaea like which has the ability to live in harsh environments. But returning to their primitive forms leads to disorder and ends in global collapse of the organ systems and organism which requires order in terms of differentiation which is maintained by the mitochondrial system in the eukaryotic cell and across the cells by intercellular mitochondrial transfer. Death of the organism may be due to the immortality pathway chosen by the cells locally. 2) Successful bacterial /mitochondrial invasion of the eukaryotic host will increase the mitochondrial genome and overpower the nuclear genome which may trigger apoptosis by degrading the nuclear genome and expelling it. 3) Partially successful invasion may result in the formation of cellular memory by increase in both OXPHOS and glycolysis. I propose that the treatment in septic shock should aim at activation of mitochondrial respiration thereby decreasing the aerobic glycolysis and changing the cell to its normal adult dynamic differentiation phenotype i.e all the drugs should be used as differentiation therapy. Adrenergic blockers and ascorbic acid may be the main treatment options, which are already used by some research groups. Abbrevations :, Oxidative phosphorylation (OXPHOS),Pathogen associated molecular pattern (PAMP), Danger associated molecular pattern(DAMP),Pattern recognition receptor(PRR),Toll like receptor (TLR).