Microbes have ruled the earth for more than a billion years; comparatively, we humans are just upstarts. Yet since the invention of penicillin in 1940, we have inflicted a crippling blow on many types of bacteria that make us ill or kill us.
But the bugs have struck back by activating DNA that is prone to errors when it replicates. This increases the chance that mutations will develop to fend off the mortal threat posed by antibiotics. In 2005, biochemist Floyd Romesberg of the Scripps Research Institute, near San Diego, announced that his lab had discovered a gene called LexA that switches on the error-prone DNA, enabling the microbe to mutate rapidly.
Shortly before this announcement, Romesberg presented some startling findings during a meeting at the institute I cofounded, the BioAgenda Institute. Romesberg, a short, intense man with a graying beard and an ability to explain complex ideas to nonscientists, told us that his lab had learned how to turn off LexA. Several major biotechnology figures at the meeting said to me, “This is huge.” At the time, several top-tier venture-capital firms were vying for Romesberg’s attention in hopes of starting a company. Ned David was one of the lucky cofounders who later named the company Achaogen–“achao” means “against chaos” in Latin.
Now Romesberg has announced the discovery of a molecule that inhibits LexA‘sability to cause mutations; it was found after the lab screened more than 100,000 possible compounds. The molecule also slips easily into a bacterial cell, which is critical to creating an effective tool to zap the bugs.
This new mutation killer does not prevent bacterial infections. Taken in combination with antibiotics, it would prevent the bugs from mutating in response to the antibiotics, thereby preventing resistant strains from developing. The drug could also be used to restore the effectiveness of older antibiotics that have been rendered almost useless by bacterial resistance.
Romesberg’s lab is also looking into ways to shut down mutations that cause cancer, as well as mutations in general. His interest lies in how evolution uses mutations to effect change and in how to influence and manipulate these evolutionary processes. Part of his lab focuses on using nucleotides and amino acids (beyond the 4 nucleotides and 20 amino acids found in nature) that he and others have created.
This is heady stuff, and I’ll write more about it in a future blog.
As the Borg used to say on Star Trek, “Resistance is futile!”–that is, until the bugs that have for so long ruled the earth figure out their next countermove. In the meantime, we can savor our victory.
Service, Robert F., “Resistance Is Futile,” ScienceNOW Daily News 28 March 2007