NIH awards $2.3 million grant to Umass Amherst microbiologist for TB research

The National Institutes of Health announced today that microbiologist Sloan Siegrist at the University of Massachusetts Amherst has received a five-year, $2.3 million National Institutes of Health (NIH) New Innovator Award, which supports "unusually innovative research from early career investigators," to study the bacterium that causes tuberculosis (TB).

NIH says that its "high risk, high reward" Director's Awards were created "to accelerate the pace of biomedical discoveries by supporting exceptionally creative scientists" and to "support unconventional approaches to major challenges in biomedical and behavioral research."

One such major challenge in biomedical research, Siegrist says, is the long-standing problem of TB treatment. Mycobacterium tuberculosis (Mtb) infects one-third of the world's population and kills an estimated 1.5 million people each year. While antibiotics can rapidly kill Mtb in a laboratory dish, it takes at least six months of treatment to cure a person. "Understanding this discrepancy is a vital step towards shortening TB therapy," she says.

Because antibiotics usually target growth-related processes, it has been suspected since the 1950s that a small population of Mtb cells can, by reducing their replication rate, in effect hide in a person's body during antibiotic treatment and "tolerate" it, which creates the need to prolong treatment.

Further, Siegrist adds, recent evidence suggests that mycobacterial growth rates may be variable and dynamic at different stages of the infection. Scientists widely accept that this growth question is important to better understanding and treating TB, but there has not been a way to directly test most hypotheses related to Mtb antibiotic tolerance during infection.

The microbiologist says, "It's surprisingly difficult to tell whether the cells are growing or not, and traditional methods take a very long time." To address this, she has developed fluorescent molecular probes that are taken up and incorporated only into actively dividing and growing cells. With the ability to distinguish replicating from non-replicating Mtb, physicians may be able to tailor antibiotic therapy and improve outcomes.

Over the next few years with the NIH grant support, Siegrist and colleagues will use an animal model and human samples to develop the probe further for use outside the laboratory, in clinics. "Since our approach detects Mtb growth at the single cell level, it is much faster than traditional, culture-based methods. We hope to be able to have a clear read-out within an hour."

She says of the NIH's early career grant, "It's hard to get a grant when you're first starting out, so I am very grateful to have this award. Translating things from lab to field is challenging, but this is an important problem that's worth tackling. If you have the opportunity to impact public health, you need to try it."