A possible explanation of the germicide effect of carbon dioxide in supercritical state based on molecular-biological evidence

Abstract

Supercritical carbon dioxide (CO 2) possesses germicide (bactericide and sporicide) effect. Despite of the fact, that this effect is used in industrial sterilization processes, the sterilization mechanism at molecular level is unclear. Our hypotheses can provide a molecular-biological explanation for the phenomenon. We believe that in supercritical state CO 2 reacts competitively with Met-tRNA fMet, the formation rate and the amount of formyl-methionyl-tRNA (fMet-tRNA fMet) will be diminished by irreversible substrate consumption. The fMet-tRNA fMet possesses a key role in prokaryotic protein synthesis, being almost exclusively the initiator aminoacyl-tRNA. The formed carbamoyl-methionyl-tRNA (cMet-tRNA fMet), probably stable only under pressure and high CO 2 concentration, is stabilized by forming a ternary molecular complex with the GTP-form of the translational initiation factor 2 (GTP-IF2). This complex is unable to dissociate from preinitiation 70S ribosomal complex because of strong polar binding between the protein C-2 domain and the modified initiator aminoacyl-tRNA. The IF2-fMet-tRNA fMet-blocked 70S ribosomal preinitiation complex does not decompose following the GTP hydrolysis, becoming unable to synthesize proteins. The death of the microbial cell is caused by inhibition of the protein synthesis and energetic depletion. Moreover, we propose a possible mechanism for the accumulation of cMet-tRNA fMet in the bacterial cell. Since the translational process is an important target for antibiotics, the proposed mechanism could be a work hypothesis for discovery of new antibiotics. Made by high conservative character of prokaryotic translation initiation, the proposed IF2 pathway deterioration strategy may conduct to obtaining selective (with low mammalian toxicity) antimicrobials and at the same time, with reduced possibility of the drug resistance development.