Citas bibligráficas
Vargas, M., (2019). Nuevo mecanismo de inhibición de la Oxitetraciclina durante la iniciación de la síntesis de proteínas en bacterias [Tesis, Universidad Peruana de Ciencias Aplicadas (UPC)]. http://hdl.handle.net/10757/628114
Vargas, M., Nuevo mecanismo de inhibición de la Oxitetraciclina durante la iniciación de la síntesis de proteínas en bacterias [Tesis]. PE: Universidad Peruana de Ciencias Aplicadas (UPC); 2019. http://hdl.handle.net/10757/628114
@misc{sunedu/4381904,
title = "Nuevo mecanismo de inhibición de la Oxitetraciclina durante la iniciación de la síntesis de proteínas en bacterias",
author = "Vargas Reyes, Maryhory Fiorella",
publisher = "Universidad Peruana de Ciencias Aplicadas (UPC)",
year = "2019"
}
Antibiotics have stablished an important milestone since their discovery, allowing the treatment of infectious diseases and surgical procedures otherwise considered lethal. However, recent studies show that the use of antibiotics can alter the microbiota, causing dysbiosis and leading to the development of diverse pathologies. In particular, broad- spectrum antibiotics such as Oxytetracycline (OTC) are widely used in agricultural and food industries. The relationship between the molecular mechanism of OTC and microbiota modifications is still unknown. The current model suggests that OTC inhibits the elongation phase of protein synthesis inhibitor. This phase of protein synthesis is highly conserved among bacteria and cannot explain the differentiated effect of OTC among bacterial genus. OTC could act in other phases of protein synthesis since the drug binds to 30S small ribosomal subunit. Among these, mRNA translation initiation stands out since it is represented by at least two alternative mechanisms in bacteria. The first mechanism uses initiation factors IF1, IF2 and IF3, while the second uses mainly IF1 and IF2. In the present study, OTC has been evaluated as a potential protein synthesis inhibitor acting at initiation of translation. Particularly, the study focuses in the mechanism that uses all three initiation factors employing biochemical methods and computer analysis of structural modelling. The results indicate that IF1 is susceptible to OTC, probably due to the near positioning with respect to the antibiotic in the ribosome. Consequently, OTC increases the stabilization of IF1 in the ribosome up to 40% along all intermediate initiation complexes. IF1 stabilization would inhibit of 70S initiation complex formation, suggesting a new mechanism of action for OTC during translation initiation. This finding would explain how OTC causes dysbiosis and provides further basis for future research of new antibiotics with a similar molecular mechanism.
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