Beating Superbugs

Humankind has made many medical advances in the last 75 years, but we are in danger of losing this progress. The culprit? Superbugs, also known as antibiotic-resistant bacteria.

If bacterial infections can’t effectively be treated, then even the simplest surgeries — as well as other medical procedures — become risky to perform. However, a collaboration among UW Medicine researchers and other organizations has reached a milestone in the fight against antibiotic-resistant bacteria and other organisms that cause infectious disease.

Protein Primer
To understand their work, however, it’s useful to receive a primer on proteins.

Proteins carry out the basic functions of life for all organisms, from shuttling oxygen around the body, to forming bones, to digesting food, among other activities. Each protein folds into a unique three-dimensional structure. The question is, how exactly do you figure out these structures?

First, scientists produce a protein in high-enough concentrations so that it forms a crystal, similar to how salt crystalizes. Then they blast that crystal with x-ray beams. The way the beams scatter across the crystal make it possible to decipher or “solve” the protein’s structure, which provides key information about its function.

The big news is that the collaboration, led by the Seattle Structural Genomics Center for Infectious Disease, has solved 1,000 protein structures for more than 70 parasites, bacteria and viruses that afflict humankind. It’s a huge step forward for science.

“As a result of this work, researchers around the world are pursuing novel therapeutics and vaccines for a host of diseases, including the Zika virus, tuberculosis and malaria,” says Wesley Van Voorhis, M.D., Ph.D., UW professor in the Division of Allergy and Infectious Diseases and director of UW Medicine’s Center for Emerging and Re-emerging Infectious Diseases.

Moving Into Drug Development
“Once you identify the proteins that carry out key aspects of a pathogen’s life, people can design drugs that disrupt those proteins, so the pathogen can’t infect other cells,” says David Baker, Ph.D., director of the UW Medicine-based Institute for Protein Design (IPD).

The IPD joined the collaborative because of their expertise in modeling how proteins fold and predicting their structures.

“There’s a critical need for this work in terms of drug development,” says Van Voorhis. “One of our focuses right now is addressing the superbug problem by identifying the protein structures of antibiotic resistant-bacteria.”

Proteins vs. Superbugs
Just how bad is this superbug problem? According to the Centers for Disease Control and Prevention, approximately 2 million people in the United States become infected with antibiotic-resistant bacteria each year, and 23,000 of those people die from their infections.

Vikram Mulligan, Ph.D., a senior fellow at the IPD, is on the front line of creating new drugs to combat these infections, designing peptides that inhibit antibiotic resistance. Like proteins, peptides are made of sequences of amino acids and also carry out many important biological activities for organisms.

“The idea is that these drugs would make bacteria sensitive again to conventional antibiotics,” says Mulligan. “You would take them along with penicillin, for example, to successfully treat an infection.”

So far, Mulligan has experienced success in the test tube — a peptide he designed was able to block a bacterial protein’s ability to break down penicillin. But there’s a long way to go from the test tube to the clinic.

“We have a number of steps ahead of us. One of those is ensuring our drug would not produce serious side effects. In five years, I would hope that we could move toward clinical trials,” he says.

Can you help defeat superbugs? Yes!
If your doctor prescribes antibiotics, says Van Voorhis, ask if you really need them. Antibiotics cannot fight viral infections, yet some doctors worry they’ll disappoint patients by not giving them antibiotics.

You could also make a gift to support research at UW Medicine. “We’ve solved all these wonderful structures, but we lack the funding to create a high volume of new drug candidates for antibiotic-resistant bacteria,” says Van Voorhis. “Gifts could help us address the superbug crisis in a meaningful way.”

Accelerate Research

Through a gift to the Center for Emerging and Re-emerging Infectious Diseases Advancement Fund.