Timothy Lu, a graduate student at MIT, was awarded the $30,000 Lemelson-MIT Prize for developing a bacteriophage, which, in conjunction with antibiotics, can become a potent weapon against drug resistant bacteria.
Lu has engineered bacteriophage to boost antibiotic effectiveness. The bacteriophage carries DNA that codes for factors that target bacterial gene networks, which former treatments failed to reach, and destroys bacterial antibiotic resistance mechanisms. The weakened bacterial defenses enable antibiotics to perform better. Administered together, Lu’s bacteriophage and antibiotics have the potential to eliminate nearly 30,000 times more bacteria than antibiotics alone, including cells that survive antibiotic-only treatment. This combination treatment also thwarts development of stronger antibiotic resistance, which can extend the lifetime of existing and future antibiotic drugs.
Lu also applied his work with bacteriophage to create a new technique for reducing harmful biofilms, which are slimy layers of bacteria that develop on the surfaces of medical, industrial and food processing equipment and are difficult to penetrate and remove. Current treatment methods to penetrate biofilms can involve peptides or enzymes, which must be administered systemically and are costly. Medical devices infected by biofilms, such as replacement hip joints or pacemakers, often have to be removed surgically.
Lu invented enzymatically-active bacteriophage that directly target the infection site, where they can simultaneously penetrate the biofilm’s protective slime layer and kill the bacteria underneath. “Think of it as a Trojan Horse,” he explained. “First you sneak into the bacteria and use it to overproduce enzymes precisely where they are needed most in order to overwhelm and break up the biofilm slime. Once the slime is disrupted, the bacteriophage then move in and kill the bacteria.”
“As a physician who has treated patients with resistant bacterial infections, I am well aware of the devastating effect they have on morbidity and mortality,” added Collin M. Stultz, associate professor of biomedical engineering in the Harvard-MIT Division of Health Sciences and Technology, and one of Lu’s recommenders for the award. “Tim has developed a series of methods that can be used to treat such problematic infections.”
In tests, Lu’s platform proved greater than 99.997 percent effective at destroying biofilms – a significant improvement over current treatment options. “The ultimate goal is to develop a sustainable source of antibacterial therapies that are effective and easy to produce at low cost, and will last us through the 21st century,” said Lu.
According to Lu, his engineered enzymatically-active bacteriophage could be initially applied in food processing settings to kill food-borne bacteria, such as Escherichia coli (E. coli) that contaminate spinach and cause severe illness when ingested. In line with these hopes, there is evidence that U.S. regulatory authorities are warming up to the therapeutic use of bacteriophage. For example, in 2006, the U.S. Food and Drug Administration approved the first U.S. treatment for Listeria contamination of processed meats using natural bacteriophage.