Slimy layers of bacterial growth, known as biofilms, pose a significant hazard in industrial

and medical settings. Once established, biofilms are very difficult to remove, and a great
deal of research has gone into figuring out how to prevent and eradicate them.

Results from a recent MIT study suggest a possible new source of protection against biofilm
formation: polymers found in mucus. The MIT biological engineers found that these
polymers, known as mucins, can trap bacteria and prevent them from clumping together on
a surface, rendering them harmless.

“Mucus is a material that has developed over millions of years of evolution to manage our
interactions with the microbial world. I’m sure we can find inspiration from it for new
strategies to help prevent infections and bacterial colonization,” says Katharina Ribbeck,
the Eugene Bell Career Development Assistant Professor of Biological Engineering and
senior author of the paper, which appears in the Nov. 8 online edition of the journal
Current Biology.

Mucin coatings may help prevent biofilm formation on medical devices and could also find
applications in personal hygiene: Incorporating them into products such as toothpaste or
mouthwash may supplement the body’s own defenses, especially in people whose natural
mucus has been depleted, Ribbeck says.

Lead authors of the Current Biology paper are former MIT postdoc Marina Caldara and
Ronn Friedlander, a graduate student in the Harvard-MIT Division of Health Sciences and
Technology. Other authors are Nicole Kavanaugh, an MIT graduate student in biology;
Joanna Aizenberg, a professor of materials science at Harvard University; and Kevin Foster,
a professor of evolutionary biology at the University of Oxford.

How to stop bacteria from teaming up

Mucus normally lines most of the wet surfaces of the body, including the respiratory and
digestive tracts. “The textbook view of mucus is that it forms a barrier to infection, but it’s
not at all clear how it does so,” Ribbeck says.

To investigate that question, Ribbeck and her colleagues observed the behavior of
Pseudomonas aeruginosa bacteria in a growth medium that contained soluble purified
mucins — long proteins with many sugar molecules attached.

For bacteria to effectively penetrate the mucus layer and infect the tissues below, they
need to form clusters that can adhere to the tissue surface. Clumps of bacteria are much
more difficult for the immune system to clear, because immune cells are specialized to
attack individual bacterial cells.

“In general, you want to have bacteria around, you just don’t want them to team up,”
Ribbeck says. “You want to them to be mixed with many other bacteria that are good for
you. You don’t want a single species to take over, because then they may overgrow the
system.”

In the new study, the researchers found that mucins block bacterial cluster formation by
preventing them from adhering, which is necessary for them to clump together. When
bacteria stay motile, they end up suspended in a gooey mix and can do less harm.

“The mucins have the ability to suppress virulence by keeping the cells separate. It’s like
keeping your kids in separate rooms, so they will stay out of trouble,” Ribbeck says.

However, bacteria are sometimes able to break through this defense system and cause
infections. This can be accelerated by reductions in mucus due to aging, dehydration or
chemotherapy, Ribbeck says. Or it may be that the mucus does not get replaced often
enough, as happens in the mucus-clogged lungs of cystic fibrosis patients.

The finding contradicts a long-held belief that mucus is merely a sticky substance that traps
more or less everything, says Gunnar C. Hansson, a professor of medical biochemistry at the
University of Gothenburg in Sweden. It also “opens a new window for studies of mucins and
their properties, which will help us to develop new medical therapies and biotechnological
applications,” says Hansson, who was not part of the research team.

‘Managing microbial behavior’

One advantage of using mucins as antimicrobial coatings is that the substance disarms
pathogenic bacteria without killing them. This makes it less likely that bacteria could evolve
resistance to mucins, as they do to antibiotic drugs. It would also spare the beneficial
bacteria that live on mucus membranes.

“This is a nice mechanism where you just suppress the virulence traits without killing the
bacteria,” Ribbeck says. “It’s nature’s way of managing microbial behavioral in a way that
could be useful to take advantage of.”

Her lab is now investigating exactly how mucins prevent bacteria from losing their motility,
and also how they block infection by nonmotile bacteria. Mucins seem to have wide-
ranging antimicrobial properties: Ribbeck has previously shown that they can trap viruses
and keep them from infecting cells, and she is now studying mucin interactions with other
pathogenic organisms, such as yeasts.

The research was funded by the Cystic Fibrosis Foundation, the European Research Council
and the National Science Foundation.
Mucus gets a bad rap. From fake snot toys and prank kits to Mucinex commercials
that portray mucus as obnoxious, grimy green men, the general consensus seems to
be that mucus is disgusting.

However, far from being a gross waste product, mucus plays an important role in the
immune system. And the slimy green stuff that runs out of your nose when you’re
sick is not the only mucus in your body. The average person generates more than a
liter of mucus a day, including snot, saliva, cervical mucus, as well as protective
coatings for the digestive system, urinary tract, lungs, nose, and eyes. Mucus covers
400 square meters of surface area in an adult body, roughly the same area as a
basketball court.

Mucus is over 90 percent water, but it also contains fat, salts, proteins, various
immune cells, and mucins. A mucin is a protein covered in chains of sugars that stick
out from the mucin molecule like legs on a centipede. Mucins give mucus its slippery
feel and are very effective at binding together to form gels, which enables mucus to
create a strong barrier against microbes and irritants.

Mucus performs a number of important functions to keep the body safe from
infection. New microbes constantly attempt to invade the human body, many of them
disease-causing pathogens. When fragile parts of the epithelium — the outer layer of
skin and the linings protecting organs — crack, microbes have an easy access point.
To prevent this, mucus keeps the epithelium well-lubricated. Mucus also coats the
existing entry points into the body, such as the nose, mouth and stomach, and
catches pathogens that try to get in that way. The mucins form a powerful sticky
mesh, like a glue trap that the invading microbes get stuck in, preventing them from
moving any farther into the body. Then antibodies, immune cells, antimicrobial
proteins, and bacteria-infecting viruses contained in mucus can kill the pathogens or
isolate them to prevent them from building up.

Some pathogens manage to break through the body’s defenses and cause sickness.
The body responds by ramping up mucus production, overproducing new mucus to
trap the invaders, which is then expelled. So that nose dripping like a leaky faucet is a
good thing: the constant flow of snot is like Drano working its way through a system
of pipes, taking the contaminants junking up the system with it as it goes. (And why
does snot turn green during a cold? That’s due to an enzyme released by the higher-
than-usual concentration of white blood cells in mucus during infection.)

Even when people are healthy, the body constantly produces mucus. Try swallowing,
and see how quickly the mouth refills with saliva. Mucus membranes — the surfaces
of the body lined with mucus — tend to cycle through coats of mucus in hours or even
minutes. The discarded mucus travels through the digestive system, where it helps to
lubricate human waste and move it through the intestines.
Mucus does more than trap and flush out pathogens. It lubricates the eyes so they
can blink and the throat so it can swallow. It lines the digestive system to prevent
stomach acid — which is strong enough to dissolve metal — from eating the walls of
the stomach. Cervical mucus operates as a lubricant to help sperm reach the egg
during ovulation, and then changes consistency to become a barrier, protecting the
fetus by preventing anything from getting into the uterus during pregnancy.

Even when it comes to microbes, mucus does more than it gets credit for. Most of the
body’s microbiome, the “good” microbes that live inside the body and help it
function, live in mucus. The microbes living in mucus produces vitamins that the
body uses. They also help to prevent inflammation in the digestive tract. They take up
space, so infectious microbes do not have any room to move in.

When potentially pathogenic bacteria do get into the body, mucus often does not kill
them — it tames them. One theory for how mucus does this is that, like most living
things, bacteria crave sugar, and mucins are covered in it. The bacteria feed on the
mucins’ sugar chains, and, like a tantrum-prone child, as long as they get their candy
they do not turn aggressive.

However, scientists are still learning how mucins operate. Mucins are too complex
and degradable to image or analyze accurately. Researchers are still trying to figure
out details of their structure, how they mesh, and why their properties change under
certain conditions. A better understanding of mucus could lead to new diagnostic
tools and treatments for medical problems like cystic fibrosis, which causes a thick
build up of mucus in the lungs. For something so ubiquitous and critical to human
health, mucus remains a tantalizing mystery.
 ‫كلوا التفاح على الريق؛ فإنه نضوح املعدة‬

‫صلى اهلل عليه وآله‪ :‬أربعة تزيد يف العمر‪ ...:‬وأكل التفاح باألسحار‪.‬‬

‫‪ . ١٥٩٤‬اإلمام الباقر (عليه السالم)‪ :‬إذا أردت أكل التفاح فشمه مث كله؛ فإنك إذا فعلت; ذلك أخرج من جسدك كل داء وغائلة‪،‬‬
‫ويسكن ما يوجد من قبل األرواح كلها‪.‬‬

‫‪ . ١٥٩٥‬رسول اهلل (صلى اهلل عليه وآله)‪ :‬امنع العروس يف أسبوعها من‪ :‬األلبان واخلل والكزبرة والتفاح احلامض‪...‬؛ الن الرحم تعقم‬
‫وتربد من هذه األربعة األشياء عن الولد‪ ،‬وحلصري يف ناحية البيت خري من امرأة ال تلد‪ ...‬والتفاح احلامض؛ يقطع حيضها فيصري داء‬
‫عليها‪٤ ( .‬‬

‫‪ :‬ثالثة ال تضر‪ :‬العنب الرازقي‪ ،‬وقصب السكر‪ ،‬والتفاح اللبناين‬