Streptomycin

Streptomycin is an effective antibiotic against Mycobacterium tuberculosis and is used in the study of tuberculosis (TB)^[1]. Streptomycin acts as a protein synthesis inhibitor, binding irreversibly to the small 16S rRNA of the 30S ribosomal subunit, interfering with protein synthesis ^[2]. Streptomycin originally had broad Gram-negative and Gram-positive coverage, but its spectrum of activity has been significantly narrowed due to antibiotic resistance ^[3]. Streptomycin is an aminoglycoside antibacterial drug with poor oral absorption and can be administered intramuscularly or intravenously ^[4].

In vitro, treatment of guinea pig ventricular myocytes with streptomycin (40 μM) for 2 min significantly inhibited the stretch-induced increase in Ca²⁺. The decrease in Ca²⁺ occurred 18 seconds after the application of streptomycin (n=13 cells). In all cells, the decrease in Ca²⁺ occurred in less than 60 seconds, indicating that streptomycin has a calcium homeostatic effect on cardiomyocytes ^[5]. Streptomycin (5, 50μg/ml) can effectively inhibit the survival and proliferation of Mycobacterium tuberculosis in human macrophages infected with Mycobacterium tuberculosis^[6].

In vivo, Streptomycin (50-100 mg/kg) was used to treat mice infected with Mycobacterium avium complex (MAC) by intramuscular injection for 4 weeks, which significantly reduced the MAC bacterial load in the spleen and liver, and showed partial protection in histopathological examination, but did not completely eliminate the infection. The liposome encapsulation effect of Streptomycin was better than that of the free form^[7].

References:
[1] Cohen K A, Stott K E, Munsamy V, et al. Evidence for expanding the role of streptomycin in the management of drug-resistant Mycobacterium tuberculosis[J]. Antimicrobial agents and chemotherapy, 2020, 64(9): 10.1128/aac. 00860-20.
[2] Weisblum B, Davies J. Antibiotic inhibitors of the bacterial ribosome[J]. Bacteriological reviews, 1968, 32(4_pt_2): 493-528.
[3] Guardabassi L, Courvalin P. Modes of antimicrobial action and mechanisms of bacterial resistance[J]. Antimicrobial resistance in bacteria of animal origin, 2005: 1-18.
[4] EDSON R S, TERRELL C L. The aminoglycosides: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, and sisomicin[C]//Mayo Clinic Proceedings. Elsevier, 1987, 62(10): 916-920.
[5] Gannier F, White E, Lacampagne A, et al. Streptomycin reverses a large stretch induced increase in [Ca2+] i in isolated guinea pig ventricular myocytes[J]. Cardiovascular research, 1994, 28(8): 1193-1198.
[6] Crowle A J, Sbarbaro J A, Judson F N, et al. Inhibition by streptomycin of tubercle bacilli within cultured human macrophages[J]. American Review of Respiratory Disease, 1984, 130(5): 839-844.
[7] Gangadharam P R J, Ashtekar D A, Ghori N, et al. Chemotherapeutic potential of free and liposome encapsulated streptomycin against experimental Mycobacterium avium complex infections in beige mice[J]. Journal of Antimicrobial Chemotherapy, 1991, 28(3): 425-435.