17 March 2007

Bacteria are Shifty, But Humans have Brains and May Learn to Use Them Eventually

Drug resistant bacteria may kill over 100,000 North Americans each year. Particularly worrisome at this time are drug resistant staph and TB. The traditional pharmacological approach to the problem has been to develop new classes of antibiotic drugs, or to modify existing drugs to combat bacterial resistance. That approach is both expensive and not clever--more the brute force approach. Occasionally the rare innovative thinker comes up with an alternative, more lateral approach.
A new antimicrobial approach can kill bacteria in laboratory experiments and eliminate life-threatening infections in mice by interfering with a key bacterial nutrient, according to research led by a University of Washington scientist. The joint project, conducted at the UW, the University of Iowa, and the University of Cincinnati, will be featured in the April 2 issue of the Journal of Clinical Investigation.

Bacteria are increasingly resistant to antibiotics, and existing drugs work poorly against chronic infections like those that occur in wounds, on medical devices and in the lungs of people with cystic fibrosis. For these reasons, a great deal of research is focused on finding new antibiotic compounds.

In this study, researchers took a different approach. Rather than trying to find agents that best killed bacteria in test tubes, they sought to intensify the stress imposed on microbes by one of the body's own defense mechanisms.

"The competition for iron is critical in the struggle between bacteria and host," explained the study's senior author, Pradeep Singh, associate professor of medicine and microbiology at the UW. "The body has potent defense mechanisms to keep iron away from infecting organisms, and invaders must steal some if they are to survive."

Iron is critical for the growth of bacteria and for their ability to form biofilms, slime-encased colonies of microbes that cause many chronic infections. "Because iron is so important in infection, we thought infecting bacteria might be vulnerable to interventions that target iron," explained Yukihiro Kaneko, senior fellow in microbiology at the UW and the study's lead author.

To accomplish this, the researchers used gallium, a metal very similar to iron.

"Gallium acts as a Trojan horse to iron-seeking bacteria," said Singh. "Because gallium looks like iron, invading bacteria are tricked, in a way, into taking it up. Unfortunately for the bacteria, gallium can't function like iron once it's inside bacterial cells."

Other approaches include locating bacterial signaling proteins that are vital to the normal development of bacterial resistance--and paralysing them. Weakening the bacteria in this way should make otherwise virulent organisms more vulnerable to the body's immune attack, and conventional antibiotics. As one researcher put it: "Evolution is not an unstoppable force," says [Floyd] Romesberg. "There is a biochemistry underlying it and it is subject to intervention."

Other innovative approaches may yet free medical practice from the treadmill of bacterial resistance. Using viruses to fight bacteria would be one way to get evolution to work for us.

Then again, we might get lucky from time to time. Common drugs used to fight fungal infections are being looked at as potentially powerful weapons against multiple drug resistant TB--a modern scourge. Finding drugs that have already passed through the grueling testing process, which are effective against one of the worst infections known, would be fortuitous.

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