Trojan horse strategy defeats drug-resistant bacteria

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."

The researchers showed that gallium killed microbes, and prevented the formation of biofilms. Importantly, gallium's action was intensified in low iron condition, like those that exist in the human body. Gallium was even effective against strains of Pseudomonas aeruginosa from cystic fibrosis patients that were resistant to multiple antibiotics. In mice, gallium treatment blocked both chronic and acute infections caused by this bacterium.

The idea of using gallium as a substitute for iron was developed by a group led by Bradley Britigan, a researcher at the University of Cincinnati and a co-author on this study. The general approach of targeting stresses already applied by natural defense mechanisms could be a promising new way to treat infections.

"We badly need new approaches to fight bacteria," said Singh. "The gallium strategy isn't ready for clinical use yet," he added. "However, we think this approach is promising, and we can't afford to leave any stone unturned."

Source: University of Washington

Related stories:

Gallium: A new antibacterial agent?
New antibacterial strategies are needed because more and more bacteria are antibiotic resistant and because antibiotics are not effective at eradicating chronic bacterial infections. One approach to developing new antibacterial strategies, taken by researchers from the University of Washington, Seattle, is to limit the amount of iron (Fe), which is critical for bacterial growth, to which bacteria have access.
CDC: Salmonella outbreak appears to be over
(AP) -- The government said Thursday that the salmonella outbreak that sickened at least 1,440 people appears to be over, but its ultimate source may never be known, partly because of shortcomings in the nation's food safety system.
Key site in iron metabolism aids in diagnosing anemia of chronic disease
University of Utah School of Medicine researchers have developed a new tool that facilitates diagnosis of anemia related to chronic illness, as well as diseases of iron overload. The results of a study detailing the new tool are published in the August 2008 issue of the journal Cell Metabolism, a publication of Cell Press.
Just dive in: Natural product hybrid provides antimicrobial and cell-resistant surfaces
(PhysOrg.com) -- Infections following treatment in clinics, retirement homes, and long-term care facilities are a grave problem for patients, and resistant germs can be particularly devastating.
Scientists discover how some bacteria may steal iron from their human hosts
Like their human hosts, bacteria need iron to survive and they must obtain that iron from the environment. While humans obtain iron primarily through the food they eat, bacteria have evolved complex and diverse mechanisms to allow them access to iron. A Syracuse University research team led by Robert Doyle, assistant professor of chemistry in The College of Arts and Sciences, discovered that some bacteria are equipped with a gene that enables them to harvest iron from their environment or human host in a unique and energy efficient manner. Doyle's discovery could provide researchers with new ways to target such diseases as tuberculosis. The research will be published in the August issue (volume 190, issue 16) of the prestigious Journal of Bacteriology, published by the American Society for Microbiology.
New research challenges notion that dinosaur soft tissues still survive
Paleontologists in 2005 hailed research that apparently showed that soft, pliable tissues had been recovered from dissolved dinosaur bones, a major finding that would substantially widen the known range of preserved biomolecules.
Scientists break record by finding northernmost hydrothermal vent field
Well inside the Arctic Circle, scientists have found black smoker vents farther north than anyone has ever seen before. The cluster of five vents – one towering nearly four stories in height – are venting water as hot as 570 F.
New protein that repairs DNA under extreme conditions
Mild environmental conditions are a prerequisite for life. Strong acids or dissolved metallic salts in high concentrations are detrimental to both humans and to simpler life forms, such as bacteria. Such conditions destroy proteins, ensuring that all biological functions in the cells come to a standstill. So what do we find at the limits of hostile conditions where we still find life? Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig (Germany) have joined up with colleagues from Spain and Great Britain to identify an enzyme that requires acids and dissolved metals in order to function. The team describes its findings regarding the extreme protein of the archaebacterium Ferroplasma acidiphilum in the latest online edition of the renowned US research journal PNAS.

News discussion:

Medicine & Health news