Creative Minds: Rapid Testing for Antibiotic Resistance

Ahmad Khalil

Ahmad (Mo) Khalil

The term “freeze-dried” may bring to mind those handy MREs (Meals Ready to Eat) consumed by legions of soldiers, astronauts, and outdoor adventurers. But if one young innovator has his way, a test that features freeze-dried biosensors may soon be a key ally in our nation’s ongoing campaign against the very serious threat of antibiotic-resistant bacterial infections.

Each year, antibiotic-resistant infections account for more than 23,000 deaths in the United States. To help tackle this challenge, Ahmad (Mo) Khalil, a researcher at Boston University, recently received an NIH Director’s New Innovator Award to develop a system that can more quickly determine whether a patient’s bacterial infection will respond best to antibiotic X or antibiotic Y—or, if the infection is actually viral rather than bacterial, no antibiotics are needed at all.

To build the foundation for his new diagnostic approach, Khalil is sequencing the transcriptomes of a variety of bacterial strains to analyze their genomic response to various antibiotics. He then uses that information to produce a panel of RNA sensors specific to each particular bacterial strain, and freeze-dries those sensors onto strips of testing paper, creating what he thinks will be a highly specific diagnostic test with a very long shelf life.

As Khalil envisions it, the clinical use of his test would involve obtaining a sample of infected material from a patient and exposing the sample to a certain antibiotic. After about 20 minutes, the sample’s cells would be lysed and the resulting solution placed on the test strip. That liquid would serve to reconstitute the freeze-dried RNA sensor reactions embedded on the paper, and those sensors would light up if the sample contains a bacterium that is a good candidate for the antibiotic. Clearly, to select the best antibiotic as quickly as possible, doctors may want to prepare several aliquots of a patient sample, expose each of them to a different antibiotic, and run several of the “freeze-dried” RNA sensor tests in parallel.

In theory, such tests could be made for virtually any combination of bacteria and antibiotic. Khalil has already succeeded in getting the sensors to identify RNA species with good sensitivity. The big challenge now is to get them to work on paper when reconstituted with liquid from lysed bacterial samples. Another major hurdle will be getting the accuracy of the tests up to the level of current antibiotic susceptibility tests, which usually take a couple of days to produce results because they involve growing bacteria from a patient’s sample in a lab dish and then exposing them to antibiotics.

As Khalil envisions it, doctors may be able to use one of his rapid paper tests to help to inform their initial recommendations regarding antibiotics and then confirm or modify those selections after they receive the results of more traditional, cell-culture tests. Currently, doctors often start by giving patients with serious infections a broad-spectrum antibiotic, which acts against a range of common bacteria. If the source of the infection proves to be one of those common bacteria that is highly sensitive, there’s a good chance the antibiotic will work. But if not, the bacterium may survive and grow more resistant to antibiotics. Not only might this make the patient’s own infection harder to treat, it could threaten the health of others by adding to our growing public health problem of antibiotic-resistant infections.

Links:

Antimicrobial (Drug) Resistance (National Institute of Allergy and Infectious Diseases/NIH)

Khalil Lab (Boston University, MA)

Khalil NIH Project Information (NIH RePORTER)

NIH Director’s New Innovator Award (Common Fund)

NIH Support:  Common Fund; National Institute of Allergy and Infectious Diseases