No one wants to risk a contagion in space. Returning home can be tricky, medical supplies are limited, crews cannot treat every complication that might arise, and a single infected astronaut could jeopardize an entire mission.

That’s especially true for any future human missions to Mars, in which an astronaut with the sniffles would be at least 33 million miles from the nearest commercial pharmacy. And while astronauts headed into space already take a ton of precautions to reduce the risk of illness, what happens if we get to the red planet and find a whole new source of infections?

Mars Season 2

No one knows whether Mars harbors microbial life today. But if the planet is inhabited by more than mere robots, those creatures could be very well be single-celled organisms tucked underground, where they’d be sheltered from harsh radiation and possibly thriving near buried geothermal systems that provide water, nutrients, and energy.

The problem is that people might also want to tap into the planet’s subterranean resources, which could expose them to potential Martian germs. And based on studies of earthly microbes, there are worrying signs that some bacteria behave especially weirdly in space. Understanding how these host-pathogen reactions change during spaceflight is crucial for long-duration voyages, like the months to years it would take to complete a human mission to Mars.

“We better figure out what the microbes are doing in response to the spaceflight environment before you just send humans up there for long-term flight,” says Cheryl Nickerson of Arizona State University.

Infection detection

In the 1960s and ‘70s, at least two Apollo missions were affected by sick crew members. In 1968, Apollo 7 commander Wally Schirra came down with a head cold 15 hours after launch. He promptly shared it with his increasingly cranky and irritated crewmates and fueled what’s been described as “a mini-mutiny.”

Later, before the infamous Apollo 13 mission launched in 1970, at least one scheduled crew member was replaced because of measles exposure. Then, during flight, a urinary tract infection bloomed in crew member Fred Haise, went painfully untreated, and progressed to a longer-term kidney infection.

To reduce the risk of off-world illnesses today, space agencies first quarantine their astronauts. Current NASA guidelines dictate that seven days before launch, astronauts enter a facility where contact is limited to approved family members and support personnel. In practice, that may still add up to between 40 and 50 people, says astronaut Samantha Cristoforetti, who has been quarantined at the Baikonur Cosmodrome in Kazakhstan.

“Many people are with us in quarantine,” she says. “We interact with other people occasionally—we should avoid physical contact, and they wear surgical masks.”

During that period, doctors routinely assess astronauts and their contacts for symptoms of infection, such as fever or a sore throat.

“While it may not sound very exciting, we’re concerned about everyday infectious diseases such as the common cold or influenza, because these are the most prevalent pathogens,” Robert Mulcahy, a physician at NASA’s Johnson Space Center, writes in an email. “We would not want something like a cold to impair the flight crew’s performance during critical operations such as launch and docking.”

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Similar procedures apply to astronauts headed into space via Russia’s Soyuz capsule, which launches from Kazakhstan. But Mulcahy and his colleagues are currently working on updating NASA’s quarantine requirements, which are presented in what’s known as the agency’s Health Stabilization Plan, to support commercial crew and future NASA missions launching from the United States.

Proposed edits include increasing the quarantine period from seven to 14 days, increasing the restrictions on direct contact between astronauts and guests, and requiring additional vaccinations for non-astronaut personnel working in the facility.

“We’ve seen a resurgence of vaccine-preventable diseases such as measles in the general U.S. population,” Mulcahy says, “so it is important to ensure a low risk of exposure to these conditions in the quarantine period.”

Feeling the strain

Protecting astronauts from preflight disease exposure is one thing, but what about the microorganisms that ultimately do hitch a ride into space, whether inside or outside of a human?

For decades, scientists have been studying how humans and microbes respond to microgravity, which might also be relevant to the lower gravity experienced on Mars. While the exact mechanisms governing those responses are not yet fully understood, observations suggest that spaceflight alters the ongoing arms race between infectious microbes and immune systems, potentially tipping the scales in favor of infection.

Being in lower gravity can weaken the human immune system and make us more susceptible to disease, according to this research. At the same time, microgravity also appears to change how microbes respond to stresses, in some cases boosting their disease-causing potential and their resistance to countermeasures. Dozens of studies, conducted both in space and in simulated microgravity on Earth, suggested that spaceflight affects how some bacteria respond to their environmental.

“It was actually quite surprising to see a change in virulence for a microorganism in spaceflight,” Nickerson says. Her lab has demonstrated that a particular strain of Salmonella Typhimurium, which is responsible for nasty food-borne illnesses in humans, becomes more virulent after spending time in microgravity.

In 2006, they sent Salmonella into orbit aboard the space shuttle Atlantis. While Nickerson and her team grew cultures on Earth, astronauts grew Salmonella in space. When the shuttle returned to Earth, Nickerson infected mice with Salmonella that had stayed on Earth and Salmonella that went into orbit.

The result? Spaceflight had increased Salmonella’s virulence, helping it kill mice faster and at lower doses. But, Nickerson is careful to note, the effect was transient.

“This was a short-duration experiment,” she says. “This was not a permanent, heritable change. The bacteria were simply adapting to their environment, and when you take them out of that environment, they change how they’re adapting. … That’s what bacteria do for a living, that’s what they do when they infect us anywhere.”

Further work revealed that microgravity mimics an environmental signal that Salmonella normally encounter—namely, a decrease in the amount of force generated by liquids moving over the cells’ surface, which signals to the cells that it is time to begin infection. On Earth, that relative calm might occur in a nice, protected pocket of lung or intestine, but in space, it’s basically everywhere.

“No one had shown that before,” Nickerson says. “No one had thought about a physical force changing the virulence or pathogenicity of an organism.”

All clogged up

But so far, Salmonella is the only microbe in which a spaceflight-induced increase in virulence has been demonstrated in a live animal. But numerous other studies have suggested that spaceflight changes microbial growth, size, metabolism, antimicrobial resistance, and other characteristics.

These experiments, done both in space and in simulated microgravity, tested well-known microbes such as E. coli, Yersinia pestis (the culprit behind plague), Streptococcus mutans, Staphylococcus aureus, Bacillus subtilis, and Candida albicans, the fungus responsible for yeast infections. Some of these studies suggest that other microbes might become virulent in microgravity, while others point to the opposite or no response.

“Multiple experiments over the past 50 years have indicated unique microbial responses when microorganisms are cultured during spaceflight, including changes in growth kinetics, antibiotic resistance, and biofilm formation,” reports NASA’s Mark Ott.

Biofilms, notably, can present major problems both for human health and environmental systems. These conglomerates of microbes latch onto surfaces and grow synergistically, forming complex layered structures that can boost the bugs’ resistance to immune defenses and environmental insults. As a result, they are notoriously difficult to treat inside humans and are responsible for clogging and degrading crucial space station infrastructure.

“The majority of bacteria in nature exist in surface-associated microbial communities,” Rensselaer Polytechnic Institute’s Cynthia Collins and colleagues wrote in a recent paper. “Abundant biofilms were found in the Russian Mir space station and were responsible for increased corrosion and a blocked water purification system.”

In 2011, Collins and her colleagues sent Pseudomonas aeruginosa—the microbe responsible for astronaut Fred Haise’s inflight discomfort—into space aboard the space shuttle Atlantis. There, Pseudomonas readily grew into biofilms that were thicker and more massive than their Earth-based counterparts and they exhibited what scientists described as “a column-and-canopy structure that has not been observed on Earth.”

Based on other studies, not only are bacteria growing in space, but changes in their growth and behavior might be making the microbes more difficult to kill. E.coli, in particular, has shown a pronounced increase in antibiotic resistance while in orbit, a result derived from an experiment performed in 1982 aboard the Soviet space station Salyut 7.

More recently, astronauts Terry Virts and Jeff Williams swabbed eight surfaces inside the International Space Station—including the dining table, crew quarters, and the waste and hygiene compartment—and sent the swabs back to Earth for culturing.

“The ISS is not a sterile environment,” Mulcahy says. “The astronauts perform regular cleaning, just like you would at home.”

When a group based at the Jet Propulsion Laboratory grew microorganisms from those cultures and sequenced their genes, they found that many of the cultures, including nine pathogenic organisms, exhibited resistance to multiple antibiotics, including penicillin. Sequencing also revealed the potential for resistance to additional antibiotics, although that has not yet been experimentally verified, nor has spaceflight been proven to be the culprit in boosting resistance.

Still, even if modern Mars is barren and lifeless after all, keeping any future human habitations clean will be key, as will understanding the best ways to battle earthly germs that might flourish in microgravity.