## 1 Introduction  
Despite the development and widespread use of antibiotics, bacteria have the upper hand against humans. Currently, many sectors worldwide, including healthcare and commercial, face a serious crisis in the effective treatment of bacterial infection, reaching the point where cocktails of different antibiotics are needed against infectious bacteria. Because of the inherently enormous selective pressure of antibiotics, bacteria readily acquire antibiotic resistance, which can be attributed to antibiotic uptake inhibition, a change in the target or mechanism of action, or direct degradation, particularly of ribosome-targeting antibiotics [1; 2; 3]. The bacterial ribosome is a major target of antibiotics, as its inhibition results in the cessation of protein synthesis. Ribosome-targeting antibiotics, such as the aminoglycos-antibiotic streptomycin, which was the first discovered, block protein synthesis by binding to functionally important regions of bacterial rRNA of the small 305 ribosomal subunit [4; 5]. The streptomycin-binding sites comprise 165 rRNA helices 11, 18, 27, and 44 and ribosomal protein S12. Streptomycin induces significant local distortion of 165 rRNA, including the crucial bases A1492 and A1493 of helix 44, which directly participate in codon recognition, thereby disrupting protein synthesis [5]. Streptomycin was first used in 1943, and the first streptomycin-resistant strain appeared in 1946 [6]. Since the initial discovery, streptomycin (Sm) resistance mechanisms have been constantly elucidated. Before 1950, [PERSON] and Finland reported Sm-pseudo-dependent (SmP), Sm-dependent (SmD), and Sm-resistant (SmR) phenotypes with streptomycin in a concentration range of 0-50,000 \(\upmu\)g/mL in four bacteria [7; 8]. SmD mutants grow at a specific threshold concentration of streptomycin, for example, 50 and 12.5 \(\upmu\)g/mL for _Staphylococcus aureus_ and _Escherichia coli_, respectively. Further, [PERSON] and [PERSON] reported three classes of streptomycin-resistant bacteria depending on the concentration, termed very low resistance, low resistance, and high resistance, that occurred spontaneously and induced _Streptococci_ and _Pneumococci_ mutants [9]. In the 1970s, [PERSON] and [PERSON] reported physiological studies of SmD mutants using transcription and translation rates and mRNA degradation [10]. According to modern research, SmR mutant strains have two phenotypic differences: (1) a low-level resistant phenotype derived from mutations in two genes, _rsmG_ and _mthA_, which encode a methyltransferase of 16S rRNA and a methylthioadenosine nucleosidase in the S-adenosylmethionine (SAM) recycling pathway, respectively; and (2) a high-level resistant phenotype caused by the mutation of _rpsL_, which encodes a ribosomal S12 component [11; 12]. Antibiotic resistance is often conferred by the addition of a methyl group at the antibiotic-binding site in the rRNA region through its own specific methyltransferase enzyme. RsmG is an AdoMet-dependent methyltransferase responsible for the synthesis of m\({}^{2}\)G527 in the 530 loop of bacterial 16S rRNA [13]. The 530 loop region is universally conserved and plays a key role in ribosomal accuracy; it is also a target of streptomycin binding, especially at nucleotides G526 and G527 [14]. Thus, when conserved _rsmG_ is mutated, bacteria such as _Escherichia coli_, _Mycobacterium tuberculosis_, _Bacillus subtilis_, and _Streptomyces coelicolor_ exhibit low-level resistance to 100 \(\upmu\)g/mL streptomycin as well as either an increase or decrease in mRNA misreading [13; 15; 16; 17]. In contrast to the low-level resistant phenotype, the high-level SmR phenotype, which is caused by a mutation in the ribosomal component RpsL, a ribosomal S12 protein of _B. subtilis_ mutant strains, revealed a resistance phenotype exceeding a streptomycin concentration of 10,000 \(\upmu\)g/mL [16]. Further, the accumulation of mutations in _rpsL_, _mthA_, and _rpoB_ confers a greater SmR phenotype and increases antibiotic production in _Bacillus_[12; 16].