On January 10, 2015, the University of Chicago’s Institute for Molecular Engineering (IME) went to space. Specifically, a polymer synthesized in Founding Pritzker Director Matthew Tirrell’s lab traveled aboard the SpaceX Dragon Lab capsule, a resupply mission destined for the International Space Station. The polymer was part of an experiment by the Arizona State University Biodesign Institute to study bacteria in low gravity, and represented the culmination of several years of collaboration.
IME Fellow Dr. John Alverdy at the UChicago Pritzker School of Medicine previously discovered a polymer known as PEG 15-20 which, when modified, reduced the tendency for bacteria to cause deadly infections, a trait known as virulence. When the Tirrell Lab arrived at the IME, the Alverdy lab asked for their help in designing a more effective variant.
Dr. Alverdy, a specialist in gastrointestinal surgery, discovered that the polymer reduces virulence while searching for a solution to a common problem in his field.
During surgery, there is a high risk of infection through exposure to the bacteria in the gut, which can cause serious infections if the bacteria spread into the blood. Prescribing antibiotics, while decreasing the rate of overall infections, has greatly increased the prevalence of antibiotic-resistant infections during gastrointestinal surgery—infections like Clostridium difficile, commonly known as C. diff.
According to the Center for Disease Control, deaths from gastrointestinal infections more than doubled from 1999 to 2007, from 7,000 a year to more than 17,000.
The new polymer was a breakthrough because it suppresses virulence without affecting the lifespan of the bacteria. Using the polymer means surgery with less chance of infection and without the use of any antibiotics, greatly reducing the risk of the worst-case scenario—developing an antibiotic resistant infection.
Prior to surgery, the patient drinks a polymer-filled drink, coating the inside of the intestines and calming any infection-prone bacteria. Once the surgery is over, the polymer passes through their system, leaving behind a healthy biome inside of the gut.
The Tirrell group began working with Dr. Alverdy and improved upon the original polymer. The preliminary experiments included limited mouse trials, where mice were deliberately infected with antibiotic resistant bacteria and then treated with polymer or left to fight the infection on their own. Within three days, 80% of the control mice died, while every single mouse treated with polymer survived the infection.
Work since that time has resulted in a polymer that is as effective as the original polymer at 1,000 times lower concentrations. The researchers believe that it works through a combination of the polymer’s interactions with the cell membranes and bacterial signaling molecules as well as its supply of phosphates, which have been shown to reduce bacterial virulence.
The polymer traveled to space as a part of an experiment on bacterial virulence in microgravity. For more than 10 years, Professor Cheryl Nickerson at Arizona State University has been studying the strange phenomenon that bacteria become more infectious in microgravity.
By studying the changes of bacterial virulence in space, the Nickerson Lab hoped to gain understanding of what gene expressions cause changes in virulence and why the bacteria are more commonly antibiotic resistant.
Their next mission was PHOENIX, or the Pathogen HOst ENteric Interactions eXperiment. Aboard the ISS, Italian astronaut Samantha Christoforetti was expected to expose a common type of worm to infectious bacteria under varying conditions. One of those conditions was in the presence of the Tirrell/Alverdy group polymer, and was to help determine the polymer’s effect on virulence and gene expression.
PHOENIX was scheduled to launch on January 10 from Kennedy Space Center. Once it arrived on the ISS, Christoforetti operated the apparatus, carefully adding the infectious bacteria to the worm cultures without posing risk to the astronauts on board. Video monitoring was used to record the lifespan of the worms for 14 days when the capsule returned to Earth for genetic analysis.