Glycoprotein Films: A Sweet Defense Against Infectious DiseaseMarch 2012
Topics: Disease Transmission, Epidemiology, Pharmacology, Health Innovation
The discovery of antibiotics was a huge leap forward in the battle against infectious diseases. But widespread and unwise use of antibiotics has led to an explosion in the number of drug-resistant pathogen strains. In search of a new tool against infectious diseases, researchers are studying how to take advantage of an age-old strategy employed by nature—using sugar decoys to prevent pathogens from attaching to our cells and infecting us.
Downside of a Miracle
Antibiotics were the miracle drugs of the 20th century. They tamed infectious bacterial diseases like dysentery, tuberculosis, and pneumonia that had been scourges of humanity since before the dawn of recorded history. Also, antibiotics have been one of the most important factors in the increase of human life expectancy by more than a decade since their invention and widespread use began in the middle of the 20th century.
However, overuse and misuse of antibiotics has led to the specter of new incurable diseases. These diseases result from the rapid emergence of strains of bacteria that are resistant to all known antibiotics. One reason for this is that antibiotics act by killing members of a pathogenic species that are vulnerable to the drug, but leaving behind resistant strains.
A Naturally Sweet Solution
Fortunately, a time-tested strategy exists that might solve this problem, a way to keep pathogens at bay without killing them and forcing them to evolve so rapidly. This strategy takes advantage of the fact that bacteria—and viruses as well—have evolved over millions of years to grab on to the naturally occurring human sugars that project densely from the surfaces of our cells.
Researchers at MITRE and other institutions believe we might employ these sugars, much as our bodies do, to "decoy" bacteria, without killing them and leaving the more robust survivors behind to attack human populations later. Thus, even though human sugars may not always taste sweet, we might be able to use them to achieve the "sweet" outcome of taming the microbial monsters we've created through the improper use of antibiotics.
The constantly evolving nature of pathogens requires pharmaceutical researchers to continually develop new antibiotics. But human cells decorate their surfaces with a limited number of unique sequences of about seven different sugars. To infect a cell, a pathogen must bind to at least one of those unique sugar chains. Once we've characterized all of the sugar chains that coat our cells, we can design a cocktail of decoys that will prevent most pathogens from latching on to a human cell surface.
During the past three decades, the pharmaceutical industry has used genetically modified organisms to mass-produce human proteins such as insulin. Someday this technology may make it possible to engineer genetically modified cells that will mass-produce inexpensive glycoproteins bearing anti-adhesive sugar decoys that could treat or prevent deadly diseases.
However, scientists don't yet know how many different sugar structures a pathogen binds to during the process of infecting human tissue. As sweet as a sugar solution may sound today, until we have more knowledge about the glycobiology of infectious disease, we won't be able to replace antibiotics with anti-adhesive drugs.
Caught on Films
Investigators at MITRE have developed ultra-thin glycoprotein films coated on one side with oil and on the other with closely packed, branching sugar chains. The films roll into balls or "micelles" that are coated with sugar chains facing outward in every direction, poised to bind tightly to a pathogen that passes by. Using a suite of micelles coated with different human sugar sequences, MITRE hopes to find out which ones a pathogen binds to during the process of infection. Once we know this, we can design micelle decoys that block all of a pathogen's hooks and thus prevent infection.
MITRE's glycoprotein films can also be used as disinfectants. For example, damp cloth wipes coated with a glycoprotein film will remove pathogens from solid surfaces without leaving behind an infectious trail. In a pilot study conducted in MITRE's Bio-Nanotechnology Lab, the author and her collaborators demonstrated the ability to remove a plant toxin from an enameled plate using a dampened cloth coated with a glycoprotein film. An untreated damp cloth couldn't wipe the toxin off the plate; however, a damp cloth coated with a glycoprotein film left no trace of toxin behind.
Those experimental results inspired hope that hospitals might someday use glycoprotein-treated wipes to remove bacteria that have become resistant to antiseptic cleansers. Disposable curtains coated with a glycoprotein film might remove infectious particles from the air in operating rooms and in wards where patients with highly contagious diseases have been isolated. Healthcare workers exposed to deadly diseases could rinse their eyes and throats with suspensions of sterile glycoprotein micelles coated with a suite of human sugar decoys.
Meanwhile, MITRE's glycoprotein films can be used as tools to discern which adhesive proteins a pathogen produces under certain environmental conditions. Once we know which strategies pathogens use to establish an infection, scientists can design decoys to block their binding to human tissue.
By pairing this 21st century innovation with the miracle drugs of the 20th century, we may be able to keep multidrug-resistant pathogens at bay while we enjoy a long and healthy life.
—by Elaine Mullen