Friday, March 6, 2009

U.S. researchers combat antibiotic resistance with engineered viruses

WASHINGTON, March 2 (Chinese media) -- A new approach to fight bacterial

infections, developed at the Massachusetts Institute of Technology (MIT) and the

Boston University (BU), could help prevent bacteria from developing antibiotic

resistance and kill those that have already become resistant.



Researchers from both schools have engineered a virus that knocks out

bacterial defense systems, enhances the effectiveness of antibiotics. The work

is reported Monday in the online issue of the Proceedings of the National

Academy of Sciences (PNAS).

Antibiotic-resistant bacteria poses a serious and growing health risk. The

U.S. Centers for Disease Control and Prevention estimated that the

antibiotic-resistant bacterium MRSA, or methicillin-resistant Staphylococcus

aureus, causes about 94,000 infections and contributes to 19,000 deaths annually

in the United States.

New drugs are needed to combat these super bugs, but very few new

antibiotics have been developed in the past few decades. "There are a lot of

targets to go after, but people haven't been able to find the drugs," said

Timothy Lu, lead author of the paper and an MD candidate in the Harvard-MIT

Division of Health Sciences and Technology.

Lu and James Collins, Howard Hughes Medical Institute investigator and

professor of biomedical engineering at BU, took anew approach: engineering

existing bacteriophages (viruses that infect bacteria) to attack specific

targets. "It's much easier to modify phages than to invent a new drug," said Lu.



The engineered viruses described in the PNAS paper attack the SOS system, a

bacterial DNA repair system enlisted when bacteria are exposed to antibiotics

that damage DNA, and other gene networks. Used in conjunction with traditional

antibiotics, the viruses undermine bacterial defense systems and prevent

resistance from developing.

The researchers tested their phages with three major classes of antibiotics

(quinolones, beta-lactams and aminoglyclosides) and had good results with all

three. In mice infected with bacteria, those treated with both engineered

bacteriophage and antibiotics had an 80 percent survival rate, compared with 50

percent for mice treated with natural bacteriophages and antibiotics, 20 percent

for mice treated only with antibiotics, and 10 percent for untreated mice.

"This work lays the groundwork for the development of a library of

bacteriophages, each designed to attack different bacterial targets," said Lu.

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