The improper and excessive use of antibiotics has led to the rise of “superbugs,” treatment-resistant bacteria causing a public health crisis of global proportions. To help combat this problem, Ahmad “Mo” Khalil, an assistant professor of biomedical engineering at the Boston University College of Engineering (ENG), has been awarded a New Innovator Award under the High-Risk, High-Reward program sponsored by the National Institutes of Health (NIH). His proposed project will focus on developing new and rapid techniques for diagnosing antibiotic resistance to more effectively manage and treat gonococcal infections.
“The Centers for Disease Control and Prevention keep a running list of high-priority antibiotic-resistant bacteria, and N. gonorrhoeae is high on that list,” says Khalil. “It’s spreading very quickly and we are basically at the last line of defense in terms of options, so being able to prescribe the proper treatment quickly is critical.”
The current clinical methods for diagnosing and treating bacterial infections rely heavily on techniques that have been around since the discovery of penicillin. When a patient presents to a clinic with an infection, a sample is taken and sent to the laboratory, where the bacteria causing the infection are grown out. To determine an effective therapy, the bacteria are then grown in a panel of antibiotics to see which one inhibits bacterial growth, a process called antibiotic susceptibility testing, or AST. It’s a long process that can take days or weeks to elicit an appropriate answer to direct the targeted therapy, which is often a luxury that providers do not have. For certain infections, such as gonorrheal infections, AST is not even performed, making it difficult to know which antibiotic will be the most effective.
Because of these issues, doctors often treat with a broad-spectrum antibiotic instead of a targeted therapy, which has contributed to the rise of antibiotic resistance. Khalil’s proposed project will reengineer AST using synthetic biology, which is the engineering of molecular and cellular systems for useful applications. The resulting technology he aims to develop will allow providers to prescribe a targeted therapy tailored to the particular organism in a matter of hours instead of days.
“When you treat susceptible bacteria with an antibiotic, they express specific RNAs that act as biomarkers that tell you the antibiotic will be an effective treatment, while resistant bacteria do not,” says Khalil. “We are going to be looking at harnessing these molecular signatures as the basis of a new form of rapid AST for N. gonorrhoeae.”
Khalil and his team, collaborating with Tufts University and MIT, will engineer synthetic RNAs to act as biosensors that can detect these specific biomarker RNAs and subsequently express a readable output, such as a color change. Next, they will create a tool that will allow clinicians to prepare a patient sample and test it on a single chip that contains RNA sensors for a full panel of antibiotics, with the best treatment options lighting up. This will provide clinicians with rapid information to determine a targeted therapy for a particular strain of gonorrhea, including antibiotic resistant strains.
In addition to providing networking opportunities for young investigators, as well as initiating access to NIH funding, the New Innovators Award will provide a monetary grant of $1.5 million direct to Khalil’s research project. Recipients of this highly selective honor are chosen based on innovative, ambitious project ideas.
“It is a testament to our department, and to the young people we are hiring, that we currently have three active NIH New Innovator Awardees: Xue Han, Wilson Wong, and now Mo Khalil,” says John A. White, professor and chair of the ENG biomedical engineering department.
“I’m overwhelmed that I was chosen for this award, and it’s a testament to my entire lab and the hard work that they are doing here at BU,” says Khalil, echoing White’s sentiments. “It’s also exciting because synthetic biology is such a new field and this award recognizes its potential to solve real-world problems.”