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.

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Creative Minds: The Human Gut Microbiome’s Top 100 Hits

Michael Fishbach

Michael Fishbach

Microbes that live in dirt often engage in their own deadly turf wars, producing a toxic mix of chemical compounds (also called “small molecules”) that can be a source of new antibiotics. When he started out in science more than a decade ago, Michael Fischbach studied these soil-dwelling microbes to look for genes involved in making these compounds.

Eventually, Fischbach, who is now at the University of California, San Francisco, came to a career-altering realization: maybe he didn’t need to dig in dirt! He hypothesized an even better way to improve human health might be found in the genes of the trillions of microorganisms that dwell in and on our bodies, known collectively as the human microbiome.

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Snapshots of Life: Portrait of a Bacterial Biofilm

Colony of Pseudomonas aeruginosa

Credit: Scott Chimileski and Roberto Kolter, Harvard Medical School, Boston

In nature, there is strength in numbers. Sometimes, those numbers also have their own unique beauty. That’s the story behind this image showing an intricate colony of millions of the single-celled bacterium Pseudomonas aeruginosa, a common culprit in the more than 700,000 hospital-acquired infections estimated to occur annually in the United States. [1]. The bacteria have self-organized into a sticky, mat-like colony called a biofilm, which allows them to cooperate with each other, adapt to changes in their environment, and ensure their survival.

In this image, the Pseudomonas biofilm has grown in a laboratory dish to about the size of a dime. Together, the millions of independent bacterial cells have created a tough extracellular matrix of secreted proteins, polysaccharide sugars, and even DNA that holds the biofilm together, stained in red. The darkened areas at the center come from the bacteria’s natural pigments.

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Portable System Uses Light to Diagnose Bacterial Infections Faster

PAD system

Caption: PAD system. Left, four optical testing cubes (blue and white) stacked on the electronic base station (white with initials); right, a smartphone with a special app to receive test results transmitted by the electronic base station.
Credit: Park et al. Sci. Adv. 2016

Every year, hundreds of thousands of Americans acquire potentially life-threatening bacterial infections while in the hospital, nursing home, or other health-care settings [1]. Such infections can be caused by a variety of bacteria, which may respond quite differently to different antibiotics. To match a patient with the most appropriate antibiotic therapy, it’s crucial to determine as quickly as possible what type of bacteria is causing his or her infection. In an effort to improve that process, an NIH-funded team is working to develop a point-of-care system and smartphone app aimed at diagnosing bacterial infections in a faster, more cost-effective manner.

The portable new system, described recently in the journal Science Advances, uses a novel light-based method for detecting telltale genetic sequences from bacteria in bodily fluids, such as blood, urine, or drainage from a skin abscess. Testing takes place within small, optical cubes that, when placed on an electronic base station, deliver test results within a couple of hours via a simple readout sent directly to a smartphone [2]. When the system was tested on clinical samples from a small number of hospitalized patients, researchers found that not only did it diagnose bacterial infections about as accurately and more swiftly than current methods, but it was also cheaper. This new system can potentially also be used to test for the presence of antibiotic-resistant bacteria and contamination of medical devices.

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Gene Expression Test Aims to Reduce Antibiotic Overuse

Doctor with ER patient

Caption: Duke physician-scientist Ephraim Tsalik assesses a patient for a respiratory infection.
Credit: Shawn Rocco/Duke Health

Without doubt, antibiotic drugs have saved hundreds of millions of lives from bacterial infections that would have otherwise been fatal. But their inappropriate use has led to the rise of antibiotic-resistant superbugs, which now infect at least 2 million Americans every year and are responsible for thousands of deaths [1]. I’ve just come from the World Economic Forum in Davos, Switzerland, where concerns about antibiotic resistance and overuse was a topic of conversation. In fact, some of the world’s biggest pharmaceutical companies issued a joint declaration at the forum, calling on governments and industry to work together to combat this growing public health threat [2].

Many people who go to the doctor suffering from respiratory symptoms expect to be given a prescription for antibiotics. Not only do such antibiotics often fail to help, they serve to fuel the development of antibiotic-resistant superbugs [3]. That’s because antibiotics are only useful in treating respiratory illnesses caused by bacteria, and have no impact on those caused by viruses (which are frequent in the wintertime). So, I’m pleased to report that a research team, partially supported by NIH, recently made progress toward a simple blood test that analyzes patterns of gene expression to determine if a patient’s respiratory symptoms likely stem from a bacterial infection, viral infection, or no infection at all.

In contrast to standard tests that look for signs of a specific infectious agent—respiratory syncytial virus (RSV) or the influenza virus, for instance—the new strategy casts a wide net that takes into account changes in the patterns of gene expression in the bloodstream, which differ depending on whether a person is fighting off a bacterial or a viral infection. As reported in Science Translational Medicine [4], Geoffrey Ginsburg, Christopher Woods, and Ephraim Tsalik of Duke University’s Center for Applied Genomics and Precision Medicine, Durham, NC, and their colleagues collected blood samples from 273 people who came to the emergency room (ER) with signs of acute respiratory illness. Standard diagnostic tests showed that 70 patients arrived in the ER with bacterial infections and 115 were battling viruses. Another 88 patients had no signs of infection, with symptoms traced instead to other health conditions.

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