Bacteria have a variety of defense mechanisms against many catastrophic stresses, including heat shock, antibiotics, and ultraviolet. Antibiotics which inhibit the growth of microorganisms are widely used for treating infectious diseases. However, bacteria often acquired resistance mechanisms to antibiotics. Resistant bacteria have various defense mechanisms, such as decreased permeability due to outer membrane changes, degradation and modification by enzymes, mutation of target molecules, and elimination by transporters.  These drug-resistant bacteria have become a big global problem.

In this study we report the novel functional polypeptides, named “r-Peptides” which are encoded in the “latent” open reading frame of E. coli "ribosomal RNA". We have shown that E. coli expresses a number of r-Peptides induced in the presence of the antibiotics by using MS/MS analysis.

Among of them, we present here the r-Peptide, r-Pep(23S-1034), encoded in the latent ORF of 23S ribosomal RNA. Interestingly, it is shown that the r-Peptide inhibited the antibacterial activity to E. coli and the anti-antibiotic activity was specific to aminoglycoside antibiotics. Also, the r-Peptide restored the kanamycin-dependent arrest of E. coli cells at the separation stage. More interestingly, the addition of r-Peptide in the presence of kanamycin significantly enhanced the formation of inclusion bodies in E. coli cells. Further proteomic analysis revealed the presence of specific chaperone proteins and heat shock proteins in these inclusion bodies. Taken together, our study suggested that the r-Peptide functioned through the induction of the expression of a specific sigma factor.