A New Weapon Against Bacterial Disease

Bacteria that are resistant to antibiotics are one of the biggest problems facing public health today. About 800,000 children worldwide die before their fifth birthday from diarrheal diseases that evade treatment. The concentration of those diseases is highest in parts of Africa and Asia.

To address the problem, CALS biochemist Srivatsan (“Vatsan”) Raman hopes to harness the power of phages—viruses that infect bacteria but leave humans unscathed. With help from a grant from the Bill and Melinda Gates Foundation, Raman’s team is designing phages to specifically target bacteria that are causing diseases in infants.

Raman describes antibiotics—how doctors usually fight infections—as hammers that take out many bacteria, both harmful and beneficial. This means they can affect the entire human microbiome, which is the community of microbes on, inside and around the human body.

“We do not yet have the tools to selectively edit the composition of a microbiome,” Raman explains. But that is one of the goals of his lab’s work with phages. Unlike antibiotics, phages are very specific. A phage only infects one type of bacterial host. It is this specificity that presents Raman and his researchers with opportunities—but also some challenges.

Phages, which resemble lunar landers, locate bacterial hosts by attaching to specific receptors on the cell’s surface. Once they have found their host, some phages, called obligate lytic phages, quickly infect the cell and replicate. Once replication is complete, the new phage progeny burst out of the cell, ready to infect and kill the next available host.

Raman’s goal is to be able to control many steps in this process. He is investigating a way to engineer a phage that can be programmed to target specific bacteria. By changing just the “legs” of the lunar lander, the designer phage can target and eliminate any bacteria the researchers wish.

However, while destruction of bacteria is the ultimate goal, the process also creates problems. Many bacteria contain toxins that are released if the bacteria die in large numbers. So Raman’s team is also trying to control the rate at which phages infect and kill cells inside the body. “We can keep the phage on a leash and determine when and where it can infect,” describes Kelly Schwartz, a postdoctoral fellow in Raman’s laboratory.

Raman believes “designer phages” have great promise for human health.

“I was drawn to this research because designer phages can provide a potential solution to the antibiotic resistance problem,” notes Raman. “These bacteria are resistant to anything you throw at them and are killers in developing countries.

“And the next question, if we are successful, is ‘How can we turn these phages into actual medications that can be delivered to these areas?’ That challenge awaits us further down the road,” Raman says.

Vatsan Raman in his lab: The biochemist is engineering viruses that can vanquish harmful bacteria. Photo by Robin Davies/UW–Madison MediaLab at Biochemistry

Ecuador: Better Health through Messaging

Some communities in Ecuador face high incidences of water-borne illness because of contaminated water or poor hygiene and sanitation. It’s a multipronged problem calling for an interdisciplinary approach combining natural, medical and social sciences. Bret Shaw, a CALS professor of life sciences communication, last year helped implement a social science approach with funding from the UW–Madison Global Health Institute.

“I used a social marketing perspective, which utilizes psychological and communication tools, to try to help villagers make lasting behavior changes in how they interact with water and sanitation,” explains Shaw.

Shaw worked with two undergraduates, Lauren Feierstein and Brenna O’Halloran, to create health behavioral prompts—small signs in Spanish left in important areas where a reminder to wash hands is vital, such as in bathrooms, near sinks and on bottles of water. Since many people in the community have limited literacy, it was important for the prompts to use images and very few words.

While the concept can seem intuitive, years of research show that the most effective prompts focus on self-efficacy—showing individuals how easy a behavior is—and making sure that the people in the graphic are relatable to the target population. The images and words Shaw’s team used were as specific as possible, showing an individual washing his or her hands with just a simple phrase underneath.

“Understanding the perspectives on why someone wouldn’t do something such as boil their water or wash their hands was very important,” says Feierstein, who also worked with residents on making and distributing organic soap. “Knowing those barriers was crucial to addressing the issue from all angles.”

The project was an extension of a course called “Water for Life Sustainability and Health,” a partnership between the Madison-based Ceiba Foundation for Tropical Conservation and the Global Health Institute. The course is led by Catherine Woodward, a faculty associate with UW–Madison’s Institute for Biology Education and president of the Ceiba Foundation. Shaw was brought in to offer guidance about how social marketing strategies can encourage healthy behavior.

“I’m a biologist and most of the people we work with are biologists, so having a communications person on board was a critical part of getting the message out,” says Woodward. “And not just about the message and having people understand why it’s a good idea to conserve natural resources—but also to actually get them to change their behavior.”