IN JUST over two weeks鈥 time, the inaugural crew of the International Space
Station moves in. But they won鈥檛 be alone. Long before the first modules of the
ISS were launched, tiny stowaways were already making themselves at home. It鈥檚 a
problem that has affected all kinds of spacecraft. Russian scientists looking at
shuttles and the ageing space station Mir discovered that they鈥檝e been playing
host to more than 250 species of microbes.
All manner of intrepid bugs could have hitched a ride to the ISS with one of
NASA鈥檚 preparation crews, or hidden away as the modules were being prepared on
the ground. Bacteria and tiny mould spores travel on flakes of dead skin and
beads of condensation, and easily float off into the station鈥檚 nooks and
crannies. And on a long-lived space station, as the ISS is intended to be, they
could happily breed in space for millions of generations.
These uninvited guests may turn out to be bad company. The descendants of
benign household moulds can wreak havoc when they set up camp inside delicate
equipment. And there鈥檚 also a more sinister possibility. Beyond the Earth鈥檚
protective ozone layer, UV radiation levels from the Sun are hundreds of times
greater, which means higher mutation rates in DNA. As the number of manned space
missions increases, so does the possibility that a returning crew will bring
back a nasty surprise in the form of a space-bred superbug. It may sound
far-fetched, but some scientists are already trying to quantify that risk.
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Russian scientists have been monitoring Mir for microscopic lodgers since the
station鈥檚 launch in 1986. Natalia Novikova of the Institute of Biomedical
Problems in Moscow says that hundreds of different species of bacteria and fungi
have been found there. 鈥淲e took swabs from the biofilms of condensation and
found lots of fungi, such as Penicillium and Aspergillus, and
bacteria, especially Staphylococcus and Bacillus,鈥 she
says.
When astronaut Michael Foale boarded Mir, one of the first things he noticed
was the all-pervasive musty smell. 快猫短视频s now know that the air was thick
with fungal spores. Where the spores settled, fungus grew, and quickly became
resistant to fungicidal wipes. It spread around every corner of the station,
under old equipment, in the wiring, anywhere that wasn鈥檛 constantly checked and
wiped.
Novikova analysed the DNA of fungus in swabs taken from Mir in 1995, and
compared it with samples collected back in 1988. The 1995 population was
certainly descended from the earlier one, but had undergone a great deal of
mutation, possibly more than would be expected on Earth in the same period of
time.
鈥淥f all microorganisms, fungus caused the worst problems because it鈥檚 not
fussy about what it gets its energy from,鈥 says Novikova. 鈥淚t can use polymers
of all kinds as a source of nutrition.鈥 What鈥檚 more, the waste products of
fungal and bacterial metabolism corrode metallic fixtures and degrade plastics.
On Mir, the rogue fungus caused all kinds of trouble, from permanently clouding
a window and eating the plastic insulation of wires, to blocking water pipes
with its sheer bulk. The main culprit was Penicillium chrysogenum, a
green powdery mould often found on old books and stale bread back on Earth.
Cleaning is a real headache on a space station. The limited ventilation makes
strong disinfectants a risk to the astronauts鈥 health. Flushing out a grimy
corner with clean water would be fine, except for the lack of gravity.
Astronauts on Mir had to gather every last rag, including balls of dirty
underwear, to scrape away the biofilms on the walls and remove every last scrap
of fungus.
This grimy environment doesn鈥檛 sound much like a holiday resort. But if the
Netherlands-based company MirCorp has its way, the first space tourist will
arrive on Mir early next year. Not surprisingly, the company is taking an
interest in the long-term ecology of the space station. It wouldn鈥檛 want its
visitors to be bugged by slimes and moulds. 鈥淲e鈥檙e spending millions of dollars
on scrubbing materials and new air filters,鈥 says Jeff Manber, president of
MirCorp.
Space sickness
Back at the ISS project, the NASA teams are concerned about the potential
risk to human health from bacteria. No one has ever got ill on a space mission,
primarily because of the introduction of pre-flight quarantine for astronauts.
But with hundreds of people鈥攁nd millions of bugs鈥攇oing into space
over the next year, it might pay to be cautious.
鈥淲e know radiation levels are high in space, we know the reaction of rapidly
growing organisms to radiation and that鈥檚 why we suspect things might happen,鈥
says Mark Ott at NASA鈥檚 Johnson Space Center in Houston, Texas. 鈥淲e鈥檙e setting
very high standards for the modules. We鈥檒l maintain fixed levels of bacteria in
the air and on surfaces by means of antiseptic wipes and detergents,鈥 Ott says.
But he admits that some bugs will survive. 鈥淪ome microbial niches are impossible
to eliminate.鈥
Colin Foale, who has written about his son Michael鈥檚 time on Mir, thinks it鈥檚
naive to expect the levels of hygiene to be much better on the ISS than they
were on Mir. 鈥淲hen a station never comes out of service for a clean, never goes
into dry dock, there鈥檚 only so much you can do,鈥 says Foale. Manber disagrees.
鈥淚 do believe it鈥檚 possible to create a more hygienic closed ecological system,鈥
he says, especially if you can build on the Russian experience.
The first experiments to monitor the growth of bacteria in space were carried
out in the early 1980s, on the Soviet Salyut stations. Soviet and French
scientists reported that the antibiotic resistance of bacteria increased during
the flight, and they noticed a change in the structure of the cell walls over
several days. The bacteria appeared to return to normal once they got back to
Earth. But the results raised the possibility that there might be something
about the space environment, perhaps the lack of gravity, which affected
bacteria. On long-term space missions, this effect, combined with a higher
mutation rate, could lead to the emergence of a new and dangerous strain.
To get a better idea of what happens to bacteria in space, Ott鈥檚 group teamed
up with Cheryl Nickerson, an expert on microbial virulence at Tulane University
in New Orleans. Nickerson exposed Salmonella typhimurium鈥攖he
bacterium that causes gastroenteritis鈥攖o microgravity. She grew her
cultures overnight in a specially designed rotating vessel, where the average
gravitational acceleration on a given bacterial cell is one-hundredth the
value of that on Earth. She hoped to get some idea of what happens to the bugs
in their first few hours on a space station.
To test the virulence of the rotated colony, Nickerson fed some of the
bacteria to mice. The results were chilling. After a few days, the liver and
spleen of mice infected with the microgravity-grown strain were simply teeming
with bacteria, between 10 and 27 times as many bugs as the controls. And the
dose of microgravity-grown Salmonella required to kill half the mice
was one-fifth that of normal gravity controls. In just ten hours, Nickerson had
grown a much more virulent bug.
So how come the microgravity-grown strain was so virulent? Surely ten hours
of growth couldn鈥檛 be long enough for random mutations to produce such a
dangerous form? Mindful of the short-term effects on bacteria from previous
space missions, Nickerson used gel electrophoresis to study the different
proteins produced by the different strains. It turned out that the microgravity
strain had much lower levels of at least 38 proteins than the normal-gravity
grown Salmonella, accounting for roughly half of all the proteins
Nickerson鈥檚 test could measure. Somehow, the genes encoding these proteins had
slowed production in the low-gravity conditions. 鈥淲e don鈥檛 know what they do,鈥
says Nickerson, 鈥渂ut with those genes partially deactivated, the organism鈥檚
capacity for virulence is greater.鈥
This sounds puzzling. It鈥檚 often by inheriting extra genes鈥攕ometimes a
whole collection on a small circular DNA structure called a plasmid鈥攖hat
previously benign bacteria become more virulent. But Nickerson points out that
virulence is a complicated genetic function. Some of the genes that were
downregulated in her low-gravity strain may normally produce proteins that
actually make the bacteria less dangerous. Antony Maurelli from the F. Edward
H茅bert School of Medicine in Bethesda, Maryland, has shown that there are
genes which seem to suppress virulence (Proceedings of the National Academy
of Sciences, vol 95, p 3943). For example, when Maurelli introduced a gene
coding for a protein called lysine decarboxylase from a non-pathogenic strain of
Escherichia coli into the dysentery bacterium Shigella, the
Shigella鈥檚 virulence was reduced.
It wasn鈥檛 clear which genes might influence the virulence of the
Salmonella bug, so Nickerson looked at the particular problems the bacteria
had to overcome as they invaded the host. Because bacteria are usually ingested,
the first thing they have to survive is the acidic environment of the stomach.
With Ott鈥檚 help, Nickerson subjected the microgravity-grown strain to acidic
conditions in a test tube. They survived the acid for several minutes longer
than the normal-gravity controls.
Nickerson also exposed the micro-gravity colony to mouse macrophages,
immune system cells whose job is to seek out and destroy foreign microorganisms
and debris. She found that in the first 20 minutes of exposure to macrophages,
nearly 100 times as many microgravity-grown bugs survived. 鈥淭hese are very
striking differences, which may be what gives the microgravity-grown culture a
head start in infection,鈥 she says. So although Nickerson can鈥檛 say for certain
what the missing proteins do, she can say that they may well inhibit virulent
activity like fighting acid and macrophages.
Other scientists are surprised by Nickerson鈥檚 result. 鈥淲hy should bacteria
like Salmonella be sensitive to microgravity?鈥 asks Maurelli. 鈥淭his is,
as far as we know, a bacterium which evolved here on Earth. It has no reason to
have a gravity sensor.鈥
Nickerson has a tentative response. She suggests that the increased virulence
in the microgravity-grown sample is reminiscent of Salmonella grown
somewhere very different鈥攊n a person. When the bacteria find themselves in
a human host, they gradually become more infectious as they adapt during the
struggle with our immune defences. Then when they pass to another person, they
are already raring to go.
Perhaps, suggests Nickerson, microgravity creates a similar pattern of
stresses on the cell walls of a bacterium as it experiences inside a person.
Once bacteria enter the stomach or bloodstream, for example, the added buoyancy
of being in a moving fluid might counter the effect of gravity on the cell
walls.
As the early space missions had suggested, Nickerson noticed that the longer
the microgravity-grown culture spent in normal gravity, the less resistant to
acid they became. 鈥淭hey seemed to revert to normal within a few hours,鈥 she
says. This sounds like good news for us Earthlings. Whatever evil things infect
astronauts on the space station, it seems that the bugs should revert to normal
fairly quickly once they touch down, making it unlikely there will be an
outbreak of space-bred infection on Earth.
But things are not that simple, says Nickerson. When a gene is inactive, it
can collect a whole series of potentially disabling mutations without any effect
on the bacterium鈥檚 survival. On a long-term space mission, a bacterium with
inactive virulence-suppressing genes might gather mutations that could leave
that strain in a permanently virulent state. But Maurelli points out that the
same argument slices both ways. 鈥淵ou could say that a bacterium that becomes
very virulent is likely to die out in the long term because it鈥檚 spending energy
fighting a host which simply isn鈥檛 there,鈥 he says. Maurelli thinks that more
work needs to be done to understand the function of the proteins that are
switched off by microgravity.
Nickerson鈥檚 next task is to try and carry out the acid and macrophage
virulence tests under microgravity conditions, to see whether the interaction
between host defences and bacteria changes. Many astronauts who return from Mir
after several months are immune-depressed, although it isn鈥檛 yet fully
understood why. 鈥淭hat combination of a deficient immune system and a more
virulent pathogen concerns me very much,鈥 says Nickerson.
So when the first starry-eyed sightseers return home from Mir, and the ISS
crews finish their shifts, could they have become the ultimate Trojan horse?
What goes up may not come down in the same form at all. Welcome home, space
bugs.
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Further Reading:
Microgravity as a novel environmental signal affecting
Salmonella enterica serovar Typhimurium virulence
by Cheryl A. Nickerson and others, in Infection and Immunity, vol 68, p 3147 (2000) -
Waystation to the Stars: the story of Mir, Michael and me
by Colin Foale (Headline, 2000)