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 of 42 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.