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Rice Magazine | Rice University

Superbugs' Super Foe

Physician Barbara Murray '69

Superbugs' Super Foe
Physician Barbara Murray '69

Physician Barbara Murray '69 works to get new antibiotics in production before resistant strains make current antibiotic

These days, it doesn’t take much to be colonized by antibiotic-resistant bacteria. A day care scuffle, a meal on vacation abroad or a short hospital stay can be enough. 

Once germs like these latch on, they may jump to other people or bloom into an infection that standard antibiotics can’t treat. There aren’t enough new antibiotics on the horizon, and public health experts warn that we may see an end to the antibiotic era in our lifetime.

Murray works in the lab, at the bedside and on the national stage to try to ward off that calamity. 

As a global expert in antibiotic resistance, Murray, a professor of internalaa medicine and an infectious diseases researcher at the University of Texas Medical School at Houston, also brings a friendly and collaborative approach to the task of understanding “superbugs.” She was elected last fall to the presidency of the Infectious Diseases Society of America (IDSA), a group of more than 10,000 infectious-disease physicians and scientists that is engaged in efforts to steer the country away from a future without antibiotics. Dangers aside, she pursues her work in large part for the thrill of discovery. 

“New things are always being discovered about infectious disease,” Murray said. “Our ability to sequence everything, and to identify even things that we can’t culture, are now opening all sorts of new doors.”

New things are always being discovered about infectious disease,” Murray said. “Our ability to sequence everything, and to identify even things that we can’t culture, are now opening all sorts of new doors.

Murray is one of the last true classic academic physicians, according to Marcus Zervos, M.D., a Wayne State University School of Medicine researcher and another expert in the field. “What we look up to is somebody who is outstanding as a teacher, as a clinician and also as a researcher, and she’s been recognized as outstanding in all of those areas,” Zervos said. 

Murray studies the intestinal superbug VRE, or vancomycin-resistant enterococcus. This germ has shown up in hospitals around the world and has been caught colonizing even healthy Greek infants. Though a less prolific killer than the notorious methicillin-resistant Staphylococcus aureus, or MRSA, it can cause devastating heart-valve infections, meningitis and other diseases in critically ill people. VRE generally resists all but two antibiotics — some strains shrug off those two as well. 

A global expert in "superbugs," Dr. Barbara Murray '69 recently testified in front of the U.S. House of Representatives' Energy and Commerce Committee on combatting the public health crisis of antibiotic resistance.

Photo: Tommy LaVergne | Rice University

Bacterial resistance to antibiotics is an ancient fact of life. Microorganisms secrete antibiotics to ward off competition; tetracycline, for example, is a natural product of soil bacteria, and penicillin famously comes from a fungus. The natural response from other species is to evolve resistance and secrete antibiotics of their own. 

Humans joined this ancient arms race when they began using antibiotics to control human infections. What began as a miracle cure for diseases like pneumonia has grown into a group of drugs we take largely for granted. But we have done so at our peril. 

Children down antibiotics for colds (which are caused by viruses and thus not cured by antibiotics), while factory-farm animals eat feed laced with the drugs; many physicians fail to prescribe the ideal antibiotic for the problem at hand. Subjecting bacteria
to so much evolutionary pressure guarantees that some will evolve to survive it. Humans must dodge these changes by stewarding the antibiotics we have and finding new ones, but, at least for now, we are
losing this race. 

“We have strains that are resistant to everything, or almost all antibiotics, and we don’t have even investigational antibiotics to use for therapy,” Zervos said. “It’s really chilling to us.”

Murray is well aware of the stakes. She helped develop a 2010 initiative to get 10 new antibiotics into production by 2020 and helped pass last year’s Generating Antibiotic Incentives Now Act to stimulate pharmaceutical companies to develop new antibiotics. Market forces in the industry select in favor of developing blockbuster drugs like Viagra, not antibiotics, which must be used sparingly. Murray and the IDSA also are helping push for the establishment of an Office of Antimicrobial Resistance, as well as for changes to federal rules that would make it easier to test experimental antibiotics.

Murray grew up in Baton Rouge, where her father taught geology at Louisiana State University. From the age of 12, she planned on a medical career. At Rice, she decided to major in math in order to broaden her horizons and graduated cum laude. Her choice of major was extremely formative, she said, for the habits of mind it instilled. 

“What math taught me,” Murray said, “was how to sit down calmly for hours and focus on a problem. When you have to prove such-and-such, and that’s all you’ve got, you just have to keep working with it and trying to figure it out and trying different paths. In infectious diseases, we’re often problem-solving and doing detective work.” 

Murray attended medical school at the University of Texas Southwestern Medical Center, graduating first in her class in 1973. She did her residency in internal medicine at Harvard’s Massachusetts General Hospital. Training stints in Costa Rica, Guatemala and Colombia convinced her to specialize in infectious diseases, and she also completed a fellowship at Massachusetts General. After six months pursuing research with the Army in Thailand, she joined the University of Texas Medical School at Houston faculty in 1980 and has risen to become director of the Division of Infectious Diseases there. 

In the 1980s, Murray was among only a few researchers interested in enterococci. They once caused so little disease that she recalls transporting a batch from Thailand using an informal VIP — Vial In Pocket — transportation method. She had a front-row seat when some strains began to evolve from ordinary fecal flora to their current deadly incarnation. 

In a series of groundbreaking discoveries, Murray and her colleagues learned what enterococci are capable of. In 1983, they were surprised to see that a strain collected from a Houston hospital patient was producing penicillinase, a substance that defends bacteria against penicillin. Penicillinase hadn’t been observed in enterococci previously, and it appeared they had borrowed the genetic instructions from an unrelated species (Staphylococcus aureus), a transaction that did not bode well. “This was really scary,” Murray recalled.

In 1991, when the team examined resistant enterococci from a group of hospital outbreaks in five mid-Atlantic states, they made another unsettling discovery: the outbreaks were caused by a single strain that had spread far and wide. Given that the organism resides in human stool, this was an unexpected and unsavory prospect. 

Murray and her team went on to pry open the enterococcal arsenal, identifying many of the bacteria’s virulence weapons, like proteins, for sticking tightly to the host. They have made some progress sidestepping VRE’s resistance, successfully immunizing rats against some virulence factors. They are now searching for substances that could inhibit the bacterium so that it passes out of the gut without doing any harm. 

In recent months, Murray has been returning to her academic roots by linking up with Rice researcher Yousif Shamoo, professor of biochemistry and cell biology and vice provost for academic affairs. Recently, they have submitted a grant to characterize the protein in enterococci that causes high-level antibiotic resistance. That information would lead to future studies to design inhibitors against that protein, Murray said.

After Murray introduced Shamoo to her former mentee, Cesar Arias, Arias and Shamoo swiftly co-authored seven papers on enterococcal resistance to the last-ditch antibiotic daptomycin — three of them with Murray. Their technique involves exposing bacteria to antibiotics, then observing in real time how the organisms tweak their genes to evolve resistance, a technique Shamoo calls evolutionary reconnaissance. 

By joining forces with cancer drug pioneer K.C. Nicolaou, Rice’s Harry C. and Olga K. Wiess Chair of Chemistry, the group hopes to design drugs that would block those predictable evolutionary changes — thus, perhaps, circumventing the antibiotic resistance problem altogether.

The researchers’ ultimate goal is to create a larger center to study infectious disease, one that would combine Rice’s research strength with the Texas Medical Center’s top-flight clinicians. Funding and a location remain uncertain. But given the group’s expertise, Murray said, “It’s the logical thing to do.”

If Murray’s colleagues are any judge, any collaboration she’s involved with stands a good chance of success. Shamoo and other researchers laud not only Murray’s science, but also her easygoing personality. Murray is generous with her time, expertise and lab resources. Both her support of younger colleagues and a focus on what would benefit her field in general, Shamoo said, are unusual in academia. “That’s the kind of person you want at the top.”

—Jenny Blair

Read more about Rice©s work with antibiotic resistance:  ricemagazine.info/237