"
Team:Carnegie Mellon/Project/Abstract
From 2013.igem.org
Abstract
Due to the widespread misuse and overuse of antibiotics, drug resistant bacteria now pose significant risks to health, agriculture and the environment. An alternative to conventional antibiotics is phage therapy. However, many temperate phage also form prophage. Our approach to antibiotic resistance is to engineer a temperate phage, Lambda, with light-activated production of superoxide. The fluorescent protein KillerRed was cloned into a plasmid vector and lambda gt11 with the IPTG inducible lac promoter. Lysogens were isolated and these strains were characterized and compared to E. coli with KillerRed from high-copy plasmids. Light activation of KillerRed resulted in decreased cell numbers. In addition, we modeled our system at multiple scales, including populations of phage and bacteria, KillerRed gene expression, ROS production, and effects of light. Having two methods of killing, lysis and superoxide, decreases the probability of developing resistance and our system overcomes the prior limitations of using wild-type temperate phages.
Impact
The Center for Disease Control (CDC) released a threat report on September 16th, 2013 on the subject of antibiotic resistant bacteria. Figure 1 shows the timeline for antibiotic discovery and antibiotic resistant strain discovery since 1940. The report identifies 3 types of resistances as "Threat Level: Urgent", 12 types of resistances as "Threat Level: Serious" and 3 types of resistances as "Threat Level: Concerning". The CDC reports 4 major steps to tackle the problem including:
- Preventing Infections, Preventing the Spread of Resistance
- Tracking
- Improving Antibiotic Prescribing/Stewardship
- Developing New Drugs and Diagnostic Tests
Unfortunately, antibiotic development have been on the decline for quite some time. There is a demand for new technologies to help effectively treat infections. Figure 2 shows the drug pipeline since 1980.
References
Antibiotic resistance threats in the United States, 2013. The Center for Disease Control. 9/16/2013.
