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New treatment discovered to cure MRSA infection

Date:
November 13, 2013
Source:
Northeastern University
Summary:
Recent work promises to overcome one of the leading public health threats of our time. In a groundbreaking study, the team presents a novel approach to treat and eliminate methicillin resistant Staphylococcus aureus, or MRSA, a potent bacterium whose resistance to antibiotics has kept it one step ahead of researchers. That is, until now.

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.
Credit: Mary Knox Merrill

Recent work from Uni­ver­sity Dis­tin­guished Pro­fessor of Biology Kim Lewis promises to over­come one of the leading public health threats of our time. In a ground­breaking study pub­lished today in the journal Nature, Lewis' team presents a novel approach to treat and elim­i­nate methi­cillin resis­tant staphy­lo­coccus aureus, or MRSA, a potent bac­terium whose resis­tance to antibi­otics has kept it one step ahead of researchers. That is, until now.

The so-​​called "superbug" infects 1 mil­lion Amer­i­cans each year. A major problem with MRSA is the devel­op­ment of deep-​​seated chronic infec­tions such as osteomyelitis (bone infec­tion), endo­carditis (heart infec­tion), or infec­tions of implanted med­ical devices. Once estab­lished, these infec­tions are often incur­able, even when appro­priate antibi­otics are used.

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 Northeastern's 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 said. "They don't do any­thing else."

Lewis and his research team posited that if they could kill these expert sur­vivors, per­haps they could cure chronic infections -- even those resis­tant to mul­tiple antibi­otics such as MRSA. Fur­ther­more, said Brian Conlon, a post­doc­toral researcher in Lewis' lab and first author on the paper, "if you can erad­i­cate the per­sis­ters, there's 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 aren't 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 said, "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 University's 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.


Story Source:

The above story is based on materials provided by Northeastern University. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. P. Conlon, E. S. Nakayasu, L. E. Fleck, M. D. Lafleur, V. M. Isabella, K. Coleman, S. N. Leonard, R. D. Smith, J. N. Adkins & K. Lewis. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature, November 2013

Cite This Page:

Northeastern University. "New treatment discovered to cure MRSA infection." ScienceDaily. ScienceDaily, 13 November 2013. <www.sciencedaily.com/releases/2013/11/131113144109.htm>.
Northeastern University. (2013, November 13). New treatment discovered to cure MRSA infection. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2013/11/131113144109.htm
Northeastern University. "New treatment discovered to cure MRSA infection." ScienceDaily. www.sciencedaily.com/releases/2013/11/131113144109.htm (accessed April 23, 2014).

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