Translation is a cellular process of protein biosynthesis according to the genetic information in mRNA. The level of incorporation of the incorrect amino acid, or mistranslation, can differ in different organisms and under different conditions. More recent research has shown that increased levels of mistranslation can have a positive effect on the cell's response to other stresses. Research on adaptation to oxidative stress is significant because oxidative stress is part of the host's immune system response to kill pathogenic bacteria. Previously, a strain of Escherichia coli bacteria was prepared with a nonfunctional isoleucyl-tRNA-synthetase editing domain, which enables increased specific mistranslation of isoleucine to structurally similar amino acids valine (Val) or norvaline (Nva). The growth of this strain was monitored and it was observed that, due to the previous mistranslation, pre-adaptation of the cells to oxidative stress occurs. Preadaptation can be related to the general response of the cell to stress, in which the protein RpoS, the sigma factor of RNA polymerase, plays a central role. In order to determine the importance of the RpoS protein in the pre-adaptation of cells due to mistranslation to oxidative stress, a mistranslating strain with an inactivated rpoS gene was prepared. The results suggest that RpoS plays an essential role in the defense of the cell against oxidative stress for bacteria precultured at lower concentrations of Val or Nva while it shows a supportive role for bacteria pre-cultured at higher concentrations of Val or Nva. It seems that under conditions of elevated mistranslation (higher concentration of Val or Nva), bacteria trigger additional mechanisms that do not depend only on the RpoS regulon, and which are sufficient for survival in oxidative stress.