INVESTIGATION OF THE MOLECULAR TARGETING MECHANISMS OF TRANS-TRANSLATION INHIBITORS AND DETERMINING THE ESSENTIAL NATURE OF TRANS-TRANSLATION IN STAPHYLOCOCCUS AUREUS
Open Access
Author:
Victor, Samjeris
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Kenneth Charles Keiler, Thesis Supervisor Dr. Wendy Hanna-Rose, Thesis Honors Advisor
Keywords:
antibiotics trans-translation Biochemistry and Molecular Biology S. aureus
Abstract:
Antibiotic-resistant bacteria have become a worldwide epidemic. Bacteria such as methicillin resistant Staphylococcus aureus and Mycobacterium tuberculosis have caused serious infectious diseases that are difficult to treat due to their antibiotic resistance. One pathway that has been identified as a potential target for antibiotics is trans-translation. This mechanism removes nonstop translation complexes where the ribosome does not terminate at a stop codon when it has reached the 3’ end of the mRNA strand. The Keiler lab has shown 46 different molecules are effective in the disruption of trans-translation, however the molecular targets for these inhibitors are unknown. The first part of this project focuses on determining the molecular target for an inhibitor molecule known as KKL-10 by using resistant mutants and genome sequencing to compare the wild-type and mutant strains. The second part of this project focuses on whether or not trans-translation is essential for the survival of S. aureus. In order to determine this, the gene that encodes for the SmpB protein (smpB), an essential protein in trans-translation, was intentionally deleted. The resulting growth of S. aureus was observed to determine whether or not the smpB gene, and thus trans-translation, is essential for bacterial survival. Demonstrating that trans-translation is essential in S. aureus will have tremendous implications in a clinical setting where MRSA infections are extremely common.