“It has been my passion for more than 40 years,” says Wallace, Chair of the Department of Microbiology at UT Health Northeast. “When I began, we knew so little about the bacteria, including how to treat them and where they come from, and there was no funding for research or treatment. I did all of my own lab work. I wrote all my own papers, and then I went to clinic. That was what most of us involved in NTM did. We had another job, and then we worked our way into it.”

The microbiology department Wallace has helped build is now a globally renowned center for excellence in susceptibility testing, molecular identification and treatment of NTM-related disease. His lab is one of the premiere sites, nationally and internationally, for DNA fingerprinting of hospital NTM outbreaks. He has published more than 150 papers related to NTM, been cited by other scholars more than 18,000 times, won multiple awards in the field, and done life-saving work developing treatments for patients with severe infections. He has also worked tirelessly to raise awareness about the prevalence and dangers of NTM, which now cause as many as 90,000 infections in the United States annually.

“Basically anywhere that you have warm water, you have these bacteria,” says Wallace.

The larger family of mycobacteria—myco is Latin for fungus—includes over 190 separate species. Of the various species, there are two very well know members. Mycobacterium tuberculosis causes tuberculosis, one of the great killers of human history. Mycobacterium leprae causes Hansen’s disease, or leprosy, a disease that was once so frightening that people suffering from it were forced to live away from everyone else in their own colonies. Most of the rest of the mycobacteria are known, collectively, as nontuberculous mycobacteria, or NTM.

Although they are not as well-known as their cousins, they are in most of our homes, typically in areas through which warm water runs, and they now cause more infections in the United States than tuberculosis and leprosy combined. The most dangerous of them can cause chronic lung infection, post-traumatic skin infection, and various other infections in immune-suppressed individuals, especially those with HIV. Patients complain of symptoms like cough, fever, blood in coughed-up mucus and lack of energy, but because those symptoms can show up in other lung conditions, doctors often miss the NTM diagnosis.

Unlike TB, NTM is not contagious, and there is no evidence of human-to-human transmission. Although it is not certain why NTM flourish in certain areas and not others, NTM infections are higher than average in East Texas, possibly because of the region's warm weather and soil conditions. It was a happy accident that Wallace ended up in Tyler, where the disease is more common than average. The growth of his research and clinical program, however, has been deliberate.

“When I started here, I was only the second lab researcher at the institution,” says Wallace, who arrived at UT Health Northeast in 1982. “Our lab was a barracks building left over from Camp Fannin and WWII.”

Over the years Wallace helped transform the clinical and research programs at UT Health Northeast. At a time when few, if any, labs did antibiotic susceptibility testing for NTM, to see if a given antibiotic would work on an infection, UT Health Northeast started offering free tests to physicians to help them decide the best course of treatment for their patients. Their accumulated collection of  distinct NTM samples, which includes almost 50,000 distinct organisms, is one of the largest in the world,  and is an invaluable resource for researchers around the world. Wallace and collaborators helped identify and name ten new species of NTM, including M. neworleansense, M. houstonense, and M. mucogenicum. They developed the standard of care treatment for Mycobacterium avium complex infection (MAC), a disease that can cause serious damage in immunosuppressed people, such as those with HIV.

The tools of his research have shifted as the technology has advanced. Where once he and his collaborators had to work with how NTM grew in a culture, new technologies like gene sequencing and high-performance liquid chromatography have allowed them to do much finer grained analysis.  This in turn has opened up new possibilities for treatment and prevention.

“Using whole genome sequencing, we found that one of these species causing MAC is acquired from the slime layers—called biofilms—of household hot water systems,” says Wallace. “They appear to grow to large numbers in the hot water tanks in the house and then spread all over the house.  Heating of the hot water tank to higher temperatures may decrease or even eliminate the MAC-causing bacteria.”

NTM remains a hard disease to treat. Most pulmonologists have limited knowledge of the disease, and symptoms often mimic those of other diseases, so some patients are never diagnosed. Others may have had the disease for years without knowing. Today, NTM is treated using harsh drugs, some of which have unpredictable side effects. NTM can also be resistant to some drug treatments. 

Wallace compares the lack of knowledge, and the challenges surrounding treatment, to where  Lyme disease was a few decades ago. 

“We forget this now, but for a long time there was no interest in Lyme disease, and very little funding,” he says. “It took a special kind of circumstance to do the work. Now everybody knows Lyme disease. Maybe someday everyone will know NTM disease.”
   
In the meantime, says Wallace, patients need to be their own best advocates when seeking help from medical professionals for NTM infections. He suggests using hospitals and treatment centers affiliated with universities, since they usually conduct research along with patient services, and often have more sophisticated knowledge of rare diseases, and possibly better treatment options. Wallace says UT Health Northeast is an example of this. 

“We may be the smallest hospital in Tyler, Texas, but we give exceptional care," he says.