Northeastern biologist Kim Lewis has received a $5.5 million grant from the National Institutes of Health (NIH) to investigate why antibiotics are not effective for certain infectious diseases. The five-year project, part of the NIH Director’s Transformative Program (T-R01), will focus on three types of disease-producing bacteria to determine how dormant subpopulations of these microorganisms survive, re-emerge and re-infect after antibiotic treatments.

 
Lewis is one of42 recipients of the T-R01 grants, a set of NIH Common Fund grants that allow scientists to propose bold, new research ideas whose pursuit may require significant resources. The grants do not have budget caps and do not require applicants to submit preliminary results.

 
“The appeal of the …T-R01 program is that investigators are encouraged to challenge the status quo with innovative ideas, while being given the necessary resources to test them,” said NIH Director Francis S. Collins.

 
Lewis and his team have discovered that pathogens responsible for chronic infections form small populations of dormant cells, known as persister cells, that are not killed by antibiotics. When antibiotic treatment ceases, persister cells grow and repopulate, causing relapse.

 
“We are investigating the molecular mechanism responsible for the formation of dormant cells that lead to antibiotic tolerance,” said Lewis, who heads the Antimicrobial Discovery Center at Northeastern. “The goal of this research is to inform the future of drug discovery, so that these currently untreatable infections can be cured.”
The research will focus on what Lewis calls the super persister phenomenon, where mutant forms of the pathogen produce more persister cells. Currently, clinical microbiology laboratories measure only the presence of active bacteria, not dormant persister cells.

 
“I hope that our work will change clinical lab practices to include tests that can detect dormant cells,” said Lewis. “These tests are available for use now and hold significant potential for better treating bacterial infections.”

 
The planned research will help identify therapies for infections that are often untreatable, such as cystic fibrosis, tuberculosis and wounds that do not heal.
The NIH awarded 115 grants, totaling $348 million, through the three innovative research programs supported by the NIH Common Fund’s Roadmap for Medical Research: the NIH Director’s Transformative R01 (T-R01) Awards, Pioneer Awards, and New Innovator Awards. The Common Fund, enacted into law by Congress through the 2006 NIH Reform Act, supports cross-cutting, trans-NIH programs with a particular emphasis on innovation and risk taking.