North­eastern Uni­ver­sity researchers have iden­ti­fied a pro­tein that enables bac­te­rial cells to sur­vive antibi­otic treatment.

This dis­covery by biology pro­fessor Kim Lewis and his team, pub­lished in the Feb­ruary 22 issue of the journal PloS (Public Library of Sci­ence) Biology, reveals for the first time the mech­a­nism by which bac­teria main­tain a chronic infec­tion in spite of aggres­sive therapy with antibiotics.

Lewis and his team pre­vi­ously dis­cov­ered that pathogens respon­sible for chronic infec­tions form small pop­u­la­tions of dor­mant cells, called per­sis­ters, which are not killed by antibi­otics. Antibi­otics func­tion only on active cells, so when treat­ment ceases, per­sis­ters grow and repop­u­late, causing a relapse. The pro­tein iden­ti­fied by the North­eastern researchers, known as TisB, trig­gers a cel­lular response that leads to the devel­op­ment of per­sister cells.

The paradox of chronic infec­tions is that, in many cases, pathogens aren’t resis­tant to antibi­otics, yet the antibi­otics don’t work,” said Lewis, director of Northeastern’s Antimi­cro­bial Dis­covery Center. “We now better under­stand what hap­pens inside the cell that enables pathogens to become inac­tive and cause relapsing infections.”

The research was con­ducted using E. coli, a common bac­terium found in food and water sup­plies, and a fre­quently pre­scribed antibi­otic, ciprofloxacin. Lewis and his team dis­cov­ered that while the antibi­otic was killing most bac­teria, it also induced pro­duc­tion of TisB in some bac­te­rial cells, which resulted in the for­ma­tion of persisters.

These find­ings rep­re­sent the first time sci­en­tists have been able to iden­tify — at the mol­e­c­ular level — how per­sister cells are formed, said Lewis.

This is the first step towards under­standing the com­plex work­ings of how cells evolve to pro­tect them­selves,” said Lewis. “The more we know, the better equipped we will be to develop counter mea­sures and effec­tive treat­ments against bac­te­rial infections.”