An Alternative to Antibiotics: Characterizing the Activation Mechanism for the Internal Late Operon Promoter in Staphylococcus aureus Phage 80⍺
Location
Access Type
Campus Access Only
Entry Number
71
Start Date
4-7-2021 2:45 PM
End Date
4-7-2021 3:00 PM
Department
Biomedical Science
Abstract
Antibiotic use in the treatment of bacterial infections is becoming more limited as resistance spreads among pathogens, including Staphylococcus aureus. An alternative to antibiotics includes a combination of bacteriophage therapies. Phages are viruses that have the potential to kill specific bacterial cells by causing them to lyse and not affecting other cells in the process. At the same time, the use of phage cocktails is highly specific, expensive, and time-consuming to develop, and phages can horizontally transfer antibiotic resistance genes among bacteria and spread the resistance further. A better approach would be activating dormant prophages already present inside the S. aureus cells leading to cell lysis. However, this approach still leads to the production of phage progeny that can spread resistance genes. Previous work has identified a unique mechanism of activating the expression of genes that prevent DNA from being packaged into the new phage particles, thus eliminating their ability to spread further and transfer resistance. However, little is known about the activating mechanisms for this late operon internal promoter. Therefore, the goal of this project is to construct a reporter plasmid with the potential promoter region fused to a bioluminescent tag to identify how it is activated. Overall, this research would help advance the use of prophage therapies when treating drug-resistant S. aureus. The broader impact of this research looks at exploiting phage pathways for targeted therapy development.
Faculty Mentor(s)
Dr. Brooks, Jamie
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An Alternative to Antibiotics: Characterizing the Activation Mechanism for the Internal Late Operon Promoter in Staphylococcus aureus Phage 80⍺
Antibiotic use in the treatment of bacterial infections is becoming more limited as resistance spreads among pathogens, including Staphylococcus aureus. An alternative to antibiotics includes a combination of bacteriophage therapies. Phages are viruses that have the potential to kill specific bacterial cells by causing them to lyse and not affecting other cells in the process. At the same time, the use of phage cocktails is highly specific, expensive, and time-consuming to develop, and phages can horizontally transfer antibiotic resistance genes among bacteria and spread the resistance further. A better approach would be activating dormant prophages already present inside the S. aureus cells leading to cell lysis. However, this approach still leads to the production of phage progeny that can spread resistance genes. Previous work has identified a unique mechanism of activating the expression of genes that prevent DNA from being packaged into the new phage particles, thus eliminating their ability to spread further and transfer resistance. However, little is known about the activating mechanisms for this late operon internal promoter. Therefore, the goal of this project is to construct a reporter plasmid with the potential promoter region fused to a bioluminescent tag to identify how it is activated. Overall, this research would help advance the use of prophage therapies when treating drug-resistant S. aureus. The broader impact of this research looks at exploiting phage pathways for targeted therapy development.