Bacteria-derived toxin could provide design for new antibiotics

As resistance to currently available antibiotics swells, new drugs are sorely needed, especially as Big Pharma's pipeline of antibiotic candidates has gone dry.

Investigators at MIT may have found the key to designing the next generation of antibiotics--a toxin called SocAB that blocks DNA replication and inhibits bacterial growth. The findings were published Nov. 14 in the journal Molecular Cell.

Sets of genes known as toxin-antitoxin (TA) systems are responsible for regulating bacterial growth. Each of these TA systems typically encodes two proteins--the toxin and the antitoxin. Under normal conditions, these proteins form a nontoxic complex, but when stressed, the antitoxin breaks down and frees up the toxin--a process that stops invading bacterial from proliferating.

In the new study, MIT's Michael Laub and his team identified a novel TA system called SocAB. SocAB is different from all other known TA systems because it targets bacterial DNA replication machinery. When the toxin, SocB, interacts with a protein called DnaN, which is involved in multiple cellular processes, it blocks DNA replication and inhibits bacterial growth. Antibiotics currently on the market do not target this DNA replication machinery.

The research suggests that antibiotics that mimic this interaction could provide the basis for a new class of drugs to treat bacterial infections.

- see the journal abstract
- read the press release