A possible explanation of the germicide effect of carbon dioxide in supercritical state based on molecular-biological evidence.
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.
András
Csaba D
CD
Department of Food Science, Sapientia Hungarian University of Transylvania from Cluj-Napoca, Faculty of Science, Miercurea Ciuc, Libertăţii Sq., Romania. csandras@mail.bme.hu
Csajági
Csaba
C
Orbán
Csongor K
CK
Albert
Csilla
C
Abrahám
Beáta
B
Miklóssy
Ildikó
I
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D001426:Bacterial Proteins / Q000378:metabolism*; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002470:Cell Survival / Q000187:drug effects; D008954:Models, Biological; D011312:Pressure; D015398:Signal Transduction / Q000187:drug effects*; D013242:Sterilization / Q000379:methods*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002245:Carbon Dioxide