EMAIL: mishaal.dayo97@gmail.com Created with ScanWritr Online editor https://www.scanwritr.com/ IzAMINOGLYCOSIDE ANTIBIOTIC The aminoglycoside antibiotics are broad spectrum antibacterial compound that are used extensively for the treatment of many bacterial infections. Aminoglycoside antibiotics are the secondary metabolites that posses the ability to kill bacteria and Jungi to gain desired effect and lessens or cure the disease their ability against human pathogens has great affinity that allowed broad clinical application against microbial infection in humans. There are lot of species of aminoglycoside is developed to avoid the harmful effect of antimicrobial ‘metabolites the first aminoglycoside were isolated from bacteria species Streptomyces and ‘micromonospora . Streptomycin is the initial species of AGA that is isolated in 1943 from bacteria species Streptomyces griseus. It was the first drug used to treat the tuberculosis and then other species was discovered slowly and gradually. At the time of their discover they show good efficacy against gram negative and some selected gram positive pathogens As the use of AGA is increased the resistance of antibiotics are observed more frequently and its adverse effect are also observed like ototoxicity and nephrotoxicity that are most common. After then their semisynthetic derivatives are prepared DIBEKACIN(1971) AMIKACIN(1972) ARBEKACIN(1973) AND NETILMICIN (1976). AFTER that the new launching of other broad spectrum antibiotics having less side effect got importance over the AGA in market e.g. Flouroquinolone carbapenemes cephalosporins.. As resistance increased to all other antibiotics specially for nosocomial infection AGA got the focus one again in clinical area particularly their use in serious gram negative infections. On the basis of chemical structure and biosynthesis AGA is divided into different classes . Structure of AGA determines its susceptibility to various aminoglycoside modifying enzyme hence the development of resistance . The general structure consist of inositol derivative linked to at least one amino sugar the whole structure containing a number of free hydroxyl and at least 2 amino group The hydroxyl and amino group which can also contain substituents that interact with RNA of 30s subunit of ribosome where they interfere with protein translation First streptomycin which is made-up of disaccharide unit linked to 4portion of guanidinylated ‘streptomycin . A large no of AGA contain 2-hydroxy streptamine which are ingredient and are biosynthetically isolated from paromamide Created with ScanWritr Online editor https://www.scanwritr.com/AGA drug that are derived from paromamide include kanamycin neomycin and gentamycin. The kanamycin consist of 4- 5 substituted and 2-DOS derivatives with 3 aminoglucose as ring C. And 2 amino or 2-6 diamimoglucose as ring B. The other class that are not derivative of paromamine are hygromycin and apramycin contain the 2- DOS unit as central core with substitution in the 5 and 4 position. UPTAKE AND MODE OF ACTION OF AMINOGLYCOSIDE. UPTAKE; Aminoglycoside penetrate in the cytoplasm of bacteria to reach their target site . Gram negative bacteria remains elusive but the way of uptake in cell has been described in three different stages. ‘According to the way 1" stage through which AGA is uptaked is generation of electrostatic interaction between positive charged AGA and negative charge lipopolysaccharide of outer bacterial ‘membrane .there are two stages energy dependent phase1 and energy dependent phase 2 EDP1: having slow rate energy dependent uptake that is correlated with AGA concentration that can be inhibited by oxidative phosphorylation or electron transport inhibitors. EDP2: involves rapid energy dependent accumulation of AGA that is followed by (EDP1) that is consuming energy from electron transport and ATP hydrolysis MODE OF ACTION; AGA is basically protein synthesis biochemical inhibitor in the molecular basis of translation . The accuracy in which translation occurs give an indication that more the codon-anticodon between the ‘mRNA and stem loop of tRNA was at heart of protein translation the essential part in the 30s ribosomal subunit consist of an asymetric internal loop made of three adenines recent study shows allosteric binding sites within ribosomes that affect the movement of ribosomal subunits which leads to inhibition off translation factor and ribosome recycling is also reduced. MECHANISM OF RESISTANCE; 165 rRNA is the main target of All AGA there are three different types of aminoglycoside modifying enzymes (AME) that modify AGAs these ATP dependent aminoglycoside phosphotransferase . The acetyl CoA dependent aminoglycoside acetyl transferase and the ATP dependent aminoglycoside nucleotidyltransferase . Improving therapeutic drug monitoring have made the AGA( aminoglycoside antibiotic) much safer for empirical and directed therapy FORTIMICIN AS NEW AMINOGLYCOSIDE. Created with ScanWritr Online editor https://www.scanwritr.com/A culture broth of micromonospora MK-70 produced two new antibiotics . Fortimicin A and 8 that is obtained on antimicrobial and paper chromatographic data with 50 treatment of fermentation beers that indicated Fortimicin A and B are new antibiotics with broad spectrum basic and water soluble . Fortimicin A produce potent unique broad spectrum antibacterial activity against gram + ve and gram -ve bacteria. Fortimicin is unstable under alkaline condition losing glycine and changes into Fortimicin 81 it is weakly active as compare to Fortimicin A. AMINOGLYCOSIDE ANTIBIOTICS INDUCES BACTERIAL BIOFILM FORMATION Biofilms are adherent aggregates of bacterial cells that forms as biotic and abiotic surfaces including human tissue. biofilms resist antibiotic treatment contribute to bacterial persistence in chronic infection. Sub inhibitory concentration of aminoglycoside antibiotics include film formation in auroginosa and escherachia coli . Which aminoglycoside response regulator was essential for this induction and contributed to bispecific AGA resistance . Tobramycin is class of aminoglycoside so tobramycin inducible biofilms formation was inhibited by exogenous GTP. There is main observation that biofilm formation can be specific , defensive reaction to the presence of antibiotics and indicates the molecular basis of this response includes alteration in the level of c-di GMP Most antibiotics of clinical use are derivatives of naturally occurring microbial products that probably function in microbial competition within environment . SPECIFIC BINDING OF AMINOGLYCOSIDE ANTIBIOTICS TO RNA Aminoglycoside antibiotics interfere with ribosomal protein synthesis with intron splicing, many observation reveals That RNA is the main target for Created with ScanWritr Online editor https://www.scanwritr.com/aminoglycoside as it interfere with protein synthesis mostly bind with ribosomal RNA rather than ribosomal protein Resistance to many antibiotics mostly that involves methylation at specific site in rRNA The antibiotics thiotreptone binds very strongly to 60 nucleotide sequence from rRNA. Aminoglycosides inhibits group 1 intron splicing by binding to specific region of RNA. The EnD. EDUCATION IS THE KEY TO BRIGHT FUTURE... Created with ScanWritr Online editor https://www.scanwritr.com/