Acquisition of Streptomycin Resistance by Oxidative Stress Induced by Hydrogen Peroxide in Radiation-Resistant Bacterium .

Streptomycin is used primarily to treat bacterial infections, including brucellosis, plague, and tuberculosis. Streptomycin resistance easily develops in numerous bacteria through the inhibition of antibiotic transfer, the production of aminoglycoside-modifying enzymes, or mutations in ribosomal components with clinical doses of streptomycin treatment. (1) Background: A transposable insertion sequence is one of the mutation agents in bacterial genomes under oxidative stress. (2) Methods: In the radiation-resistant bacterium subjected to chronic oxidative stress induced by 20 mM hydrogen peroxide, active transposition of an insertion sequence element and several point mutations in three streptomycin resistance (SmR)-related genes (, , and ) were identified. (3) Results: IS of the IS family integrated into the gene (_2335), called S, encodes a ribosomal guanosine methyltransferase resulting in streptomycin resistance. In the case of _2840-disrupted mutant strains (S1 and S2), growth inhibition under antibiotic-free conditions was recovered with increased growth yields in the presence of 50 µg/mL streptomycin due to a streptomycin-dependent (SmD) mutation. These mutants have a predicted proline-to-leucine substitution at the 91st residue of ribosomal protein S12 in the decoding center. (4) Conclusions: Our findings show that the active transposition of a unique IS element under oxidative stress conditions conferred antibiotic resistance through the disruption of . Furthermore, chronic oxidative stress induced by hydrogen peroxide also induced streptomycin resistance caused by point and frameshift mutations of streptomycin-interacting residues such as K43, K88, and P91 in RpsL and four genes for streptomycin resistance.