Researchers Discover New Treatment for MRSA Infection

Northeastern University professor Kim Lewis and his team developed a novel approach for treating chronic infections, which account for more than 20,000 deaths in the U.S. each year. Photo by Mary Knox Merrill.

Recent work from Northeastern University professor of biology Kim Lewis promises to over­come one of the leading public health threats of our time. In a ground­breaking study pub­lished Wednesday in the journal Nature, Lewis team presents a novel approach to treat and elim­i­nate methi­cillin-resis­tant Staphy­lo­coccus aureus (MRSA), a potent bac­terium whose resis­tance to antibi­otics has kept it one step ahead of researchers. That is, until now.
 
Bac­teria such as MRSA have evolved to actively resist cer­tain antibi­otics, a fact that has gen­er­ated sig­nif­i­cant interest among the sci­en­tific and med­ical com­mu­ni­ties. But Lewis, director of Northeasterns Antimi­cro­bial Dis­covery Center, sus­pected that a dif­ferent adap­tive func­tion of bac­teria might be the true cul­prit in making these infec­tions so devastating.

The new work rep­re­sents the cul­mi­na­tion of more than a decade of research on a spe­cial­ized class of cells pro­duced by all pathogens called per­sis­ters. According to Lewis, these cells evolved to sur­vive. Sur­vival is their only func­tion, he says. They dont do any­thing else.
 
Lewis and his research team posited that if they could kill these expert sur­vivors, per­haps they could cure chronic infectionseven those resis­tant to mul­tiple antibi­otics such as MRSA. Fur­ther­more, says Brian Conlon, a post­doc­toral researcher in Lewis lab and first author on the paper, if you can erad­i­cate the per­sis­ters, theres less of a chance that resis­tance will develop at all.
 
Lewis, who was elected to the Amer­ican Academy of Micro­bi­ology in 2011 for his schol­ar­ship in the field, has found that per­sis­ters achieve their sin­gular goal by entering a dor­mant state that makes them imper­vious to tra­di­tional antibi­otics. Since these drugs work by tar­geting active cel­lular func­tions, they are use­less against dor­mant per­sis­ters, which arent active at all. For this reason, per­sis­ters are crit­ical to the suc­cess of chronic infec­tions and biofilms, because as soon as a treat­ment runs its course, their reawak­ening allows for the infec­tion to estab­lish itself anew.
 
In the recent study, which also includes con­tri­bu­tions from assis­tant pro­fessor Steve Leonard of the Depart­ment of Phar­macy Prac­tice, Lewis team found that a drug called ADEP effec­tively wakes up the dor­mant cells and then ini­ti­ates a self-destruct mech­a­nism. The approach com­pletely eradicated MRSA cells in a variety of lab­o­ra­tory exper­i­ments and, impor­tantly, in a mouse model of chronic MRSA infection.
 
Cou­pling ADEP with a traditional antibiotic, Conlon noted, allowed the team to com­pletely destroy the bac­te­rial pop­u­la­tion without leaving any survivors.
 
As with all other antibi­otics, actively growing bac­te­rial cells will likely develop resis­tance to ADEP. How­ever, Lewis says, Cells that develop ADEP resis­tance become rather wimpy. That is, other tra­di­tional drugs such as rifampicin or line­zolid work well against ADEP-resistant cells, pro­viding a unique cock­tail that not only kills per­sis­ters but also elim­i­nates ADEP-resistant mutant bacteria.
 
Dr. Richard Novick of New York Universitys Lan­gone Med­ical Center and a leader in the field said the research is a bril­liant out­growth of Kim Lewis pio­neering work on bac­te­rial per­sis­ters and rep­re­sents a highly cre­ative ini­tia­tive in this era of dimin­ishing antibi­otic utility.
 
While ADEP tar­gets MRSA, Lewis team believes sim­ilar com­pounds will be useful for treating other infec­tions as well as any other dis­ease model that can only be over­come by elim­i­nating a pop­u­la­tion of rogue cells, including can­cerous tumors. They are pur­suing sev­eral already.

Source: Northeastern University