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Pathway Description
Capreomycin Action Pathway
Homo sapiens
Drug Action Pathway
Capreomycin, also known as Capastat, is an antibiotic from the aminoglycoside class. It is used as an adjunct drug in drug-resistant tuberculosis (TB). Like many antibiotics, this drug is produced by a bacteria, Streptomyces capreolus. Capreomycin's exact mechanism of action is still unclear, but it is thought to bind the 70S ribosomal unit of bacteria. It binds to the 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA. With this binding, the 16S rRNA can't interact with the 23S rRNA, this inhibits the translocation during the peptide elongation. Also, this drug affects protein synthesis by stabilizing the peptidyl-tRNA complex in the pretranslocation complex. Capreomycin is not absorbed in significant quantities from the gastrointestinal tract and must be administered parenterally (intramuscular or intravenous). The side effects are tinnitus, hearing loss, proteinuria, and renal dysfunction. As Mycobacterium Tuberculosis enters several cell types (neutrophils, macrophages, and endothelial cells) by phagocytosis, the drug is given by injection (intramuscular or intravenous).
References
Capreomycin Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Fu LM, Shinnick TM: Genome-wide exploration of the drug action of capreomycin on Mycobacterium tuberculosis using Affymetrix oligonucleotide GeneChips. J Infect. 2007 Mar;54(3):277-84. doi: 10.1016/j.jinf.2006.05.012. Epub 2006 Jul 5.
Pubmed: 16822547
Johansen SK, Maus CE, Plikaytis BB, Douthwaite S: Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs. Mol Cell. 2006 Jul 21;23(2):173-82. doi: 10.1016/j.molcel.2006.05.044.
Pubmed: 16857584
Bussi C, Gutierrez MG: Mycobacterium tuberculosis infection of host cells in space and time. FEMS Microbiol Rev. 2019 Jul 1;43(4):341-361. doi: 10.1093/femsre/fuz006.
Pubmed: 30916769
Smith I: Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev. 2003 Jul;16(3):463-96. doi: 10.1128/CMR.16.3.463-496.2003.
Pubmed: 12857778
Kalscheuer R, Palacios A, Anso I, Cifuente J, Anguita J, Jacobs WR Jr, Guerin ME, Prados-Rosales R: The Mycobacterium tuberculosis capsule: a cell structure with key implications in pathogenesis. Biochem J. 2019 Jul 18;476(14):1995-2016. doi: 10.1042/BCJ20190324.
Pubmed: 31320388
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