Researchers are interested in studying effects on the gut microbiome and antibiotic-resistant infections.
In September 2020, UW–Madison biochemists launched a small box containing viruses and bacteria into space to investigate the ways microbes such as those residing in our guts respond to space conditions. Now, the bacteria and phages (viruses that infect bacteria) have returned to Madison with hints about how space travel may impact the gut microbiome and clues about how to treat antibiotic-resistant bacterial infections on Earth.
“Our experiment was about more than learning what happens when bacteria and phages travel in outer space. We are asking questions about how mutations acquired in space might be relevant on Earth,” says biochemistry professor Vatsan Raman, who led the project. The researchers’ findings are reported in the journal PLOS Biology.
Bacteria-phage relationships are essential to maintaining a healthy balance in the human gut microbiome: Gut bacteria evolve to evade infection, and in response, phages mutate to find new ways to infect bacteria. Raman’s lab is harnessing this relationship to design phages that can compete with and combat bacterial infections.
“Space is such a unique environment,” says Philip Huss, a postdoctoral researcher in the Raman Lab and a lead author on paper. “It has the potential to reveal possibilities for how phages can evolve that are hidden on Earth.”
With scientists and astronauts spending extended periods of time in space — and the onset of recreational space travel — it’s become important to understand how environments with reduced gravity (microgravity) impact the evolutionary dance between bacteria and phages. Sustained microgravity is difficult to establish on Earth. But on the International Space Station, a space-based national laboratory, it’s possible to do research in the near-weightless conditions that are ideal for the Raman Lab’s study.
“On Earth, we know that phages move around their environment and find a bacterial host to infect. Then they enter and kill the bacteria,” explains Raman. “But in outer space, do these rules of engagement still apply? If there is no gravity, then the way that phages move around their environment will just be different. The ways they attack bacteria will be different.” The UW–Madison scientists engineered phages to exhibit thousands of different mutations and sent them to space. For 25 days, ISS scientists incubated different combinations of the phages and bacteria together and in isolation. Back in Madison, the same experiments were replicated under Earth’s gravity.
Designing an experiment for space
Designing a space-bound experiment required that the researchers stick to a prescribed set of materials that can fit in a confined space. To ensure that their study was feasible and met the safety standards of ISS research, the team partnered with Rhodium Scientific, a biotechnology company that works with researchers to facilitate scientific exploration in space.
Huss and Chutikarn Chitboonthavisuk (a former graduate student in the Raman Lab) found key differences when they compared the phages and bacteria grown in space with those grown on Earth. In space, the phages and bacteria acquired novel mutations: Proteins on the surfaces of bacteria changed and in turn, phages mutated to bind to these altered surfaces. As a result, the mutations that allowed phages to infect bacteria in space differed from those on Earth.
The Raman Lab then engineered phages with a variety of mutations that were successful in space to test their effectiveness against bacterial pathogens on Earth, putting the novel phages to work against bacteria responsible for urinary tract infections. Currently, more than 90% of the bacteria that cause UTIs are resistant to at least one antibiotic.
“We found that the novel combinations of phage mutations were really effective at killing UTI pathogens on Earth,” says Raman. “And that’s pretty surprising. Why would an experiment in space inform how to design phage therapies on Earth? We don’t exactly know, but one of our hypotheses is that the environmental factors stressing UTI bacteria somehow mimic the stress bacteria experience in microgravity, making their surface proteins similar.”
With the experience gained through their first experiment’s voyage, the researchers are now working on answering bigger questions — with experiments that must still fit in the same, small box — for a future space launch.
“First, we asked basic microbiology questions, just in space,” says Huss. “Now, we’re ready to study systems of multiple phages and bacteria that more closely represent the complexity of the human microbiome. What novel interactions occur in space, and what can we learn from them here on Earth?”
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This study was supported by funding from the Defense Threat Reduction Agency (Grant HDTRA1-16-1-0049.
The Rise of Phage Therapy: A New Frontier in Fighting Antibiotic Resistance
The escalating crisis of antibiotic resistance is arguably one of the most pressing global health challenges of our time. The World Health Organization estimates that antimicrobial resistance (AMR) causes nearly 5 million deaths annually. Traditional antibiotics are becoming increasingly ineffective against common infections, prompting a desperate search for alternative therapies. Enter phage therapy – the use of viruses that specifically target and kill bacteria.
From Space Station to Hospital Bed: The Potential of Space-Evolved Phages
The UW-Madison research highlights a fascinating avenue within phage therapy: leveraging the unique evolutionary pressures of space to create more potent phages. Microgravity, radiation, and altered immune responses in space can accelerate phage evolution, potentially yielding viruses with enhanced ability to overcome bacterial defenses. This isn’t just theoretical. Studies have shown that bacteria exposed to space conditions exhibit altered gene expression and increased mutation rates, making them more vulnerable to novel phage attacks.
Beyond UTIs: Expanding the Scope of Phage Applications
While the initial success with UTI pathogens is promising, the potential applications of space-evolved phages extend far beyond urinary tract infections. Researchers are exploring their use against a wide range of antibiotic-resistant bacteria, including Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Escherichia coli. The personalized nature of phage therapy – tailoring the viral cocktail to the specific bacterial strain infecting a patient – is a significant advantage over broad-spectrum antibiotics.
Challenges and Future Directions in Phage Therapy
Despite the excitement, several hurdles remain before phage therapy becomes mainstream. Regulatory pathways for phage-based treatments are still evolving, and large-scale clinical trials are needed to demonstrate efficacy and safety. Another challenge is the potential for bacteria to develop resistance to phages, necessitating ongoing phage engineering and the use of phage cocktails (combinations of different phages) to broaden the spectrum of activity.
Looking ahead, advancements in synthetic biology and genetic engineering will play a crucial role in optimizing phage therapy. Researchers are exploring ways to enhance phage infectivity, broaden their host range, and even engineer phages to deliver therapeutic payloads directly to bacterial cells. The convergence of space exploration and biomedical research, as exemplified by the UW-Madison study, promises to unlock new and innovative solutions to the antibiotic resistance crisis.
FAQ: Phage Therapy and the Future of Infection Control
Q: What are phages?
A: Phages are viruses that specifically infect and kill bacteria. They are naturally occurring and abundant in the environment.
Q: Is phage therapy safe?
A: Phage therapy is generally considered safe, as phages are highly specific to bacteria and do not harm human cells. However, rigorous clinical trials are necessary to confirm long-term safety.
Q: How does phage therapy differ from antibiotics?
A: Antibiotics are broad-spectrum drugs that kill a wide range of bacteria, while phages are highly specific to their bacterial targets. This specificity minimizes disruption to the gut microbiome and reduces the risk of antibiotic resistance.
Q: Will bacteria eventually become resistant to phages?
A: Yes, bacteria can develop resistance to phages, but this can be mitigated by using phage cocktails and continuously evolving new phages.
Q: What role does space research play in phage therapy?
A: Space provides a unique environment that accelerates phage evolution, potentially leading to the discovery of more potent and effective phages.
Did you know? Phages were actually discovered around the same time as antibiotics, in the early 20th century. However, their development was largely overshadowed by the success of penicillin and other antibiotics.
Pro Tip: Maintaining a healthy gut microbiome through diet and lifestyle choices can enhance your natural defenses against bacterial infections and potentially reduce the need for antibiotics.
Interested in learning more about the fight against antibiotic resistance? Explore resources from the World Health Organization and the Centers for Disease Control and Prevention.
What are your thoughts on the potential of phage therapy? Share your comments below!
