链霉素主要用于治疗细菌感染,包括布鲁氏菌病,瘟疫,和肺结核。通过抑制抗生素的转移,在许多细菌中容易产生链霉素耐药性,氨基糖苷修饰酶的生产,或临床剂量的链霉素治疗核糖体成分的突变。(1)背景:可转座插入序列是氧化应激下细菌基因组中的突变因子之一。(2)方法:在20mM过氧化氢诱导的抗辐射细菌地热异常球菌中,插入序列元件的主动转座和三个链霉素抗性(SmR)相关基因中的几个点突变(rsmG,rpsL,和mthA)被识别。(3)结果:IS5家族的ISDge6整合到rsmG基因(dgeo_2335)中,叫做SrsmG,编码核糖体鸟苷甲基转移酶,导致链霉素抗性。在dgeo_2840破坏的突变菌株(S1和S2)的情况下,由于链霉素依赖性(SmD)突变,在50µg/mL链霉素存在下,无抗生素条件下的生长抑制作用得以恢复,生长产量增加。这些突变体在解码中心的核糖体蛋白S12的第91个残基处具有预测的脯氨酸到亮氨酸的置换。(4)结论:我们的发现表明,在氧化应激条件下,独特的IS元件的主动转座通过rsmG的破坏赋予了抗生素抗性。此外,过氧化氢诱导的慢性氧化应激还诱导了链霉素抗性,该抗性是由链霉素相互作用残基如RpsL中的K43,K88和P91的点和移码突变引起的,以及链霉素抗性的4个基因.
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 Deinococcus geothermalis 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 (rsmG, rpsL, and mthA) were identified. (3) Results: ISDge6 of the IS5 family integrated into the rsmG gene (dgeo_2335), called SrsmG, encodes a ribosomal guanosine methyltransferase resulting in streptomycin resistance. In the case of dgeo_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 rsmG. 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.