Research Highlights
Probing the genes of a 'bad bug'
March 9, 2009
Acinetobacter baumannii has won a reputation as a"bad bug"—so dubbed by the Infectious Diseases Society of America for its ever-increasing ability to escape the effect of antibiotics that once thrashed the bacteria. With more than a third of A. baumannii infections considered resistant to multiple drug classes, doctors have few options for treating the defiant bug, which tends to infect severely sick, hospitalized patients and can lead to pneumonia, bloodstream infections and other dangerous conditions.
Robert Bonomo, MD, with the Louis Stokes Cleveland VA Medical Center and Case Western Reserve University (CWRU), is investigating the elaborate genetic makeup of A. baumannii—known to some as"Iraqibacter" because of the toll it has taken on wounded U.S. troops. The germ has emerged in more than 30 percent of combat-related injuries in Iraq and Afghanistan, according to a recent article in the Journal of Orthopedic Research, and has complicated the recovery of hundreds of troops. It is the threat to American forces, Bonomo says, that largely drives his research interest in the germ.
"This is a world-class challenge that is very important to our troops, and to the VA system that takes care of these men and women when they come back," he says. Why the focus on the bacteria’s genetic machinery, in particular? Further understanding these genes may make them eventual targets for antibiotics or vaccines, Bonomo explains.
In a study published in the December 2008 issue of the Journal of Bacteriology, Bonomo and lead author Mark D. Adams, PhD, associate professor of genetics at the CWRU School of Medicine, compared the genome sequences of three multidrugresistant A. baumannii isolates from infected patients at Walter Reed Army Medical Center with three drug-susceptible isolates. The study, which involved collaborators at the VA Western New York Health Care System and State University of New York at Buffalo, grew out of earlier work in which Bonomo’s lab analyzed the genetic make-up of drugresistant A. baumannii isolated from patients at the Army hospital. That study was published in 2006.
Among the researchers' questions in the latest study: What features do all isolates of A. baumannii share, and which features distinguish the genomes that cause difficult-to-treat infections?
Even very closely related isolates can carry very different set of genes, Bonomo’s team found. This can make some strains responsive to antibiotics and others resistant. The researchers determined that A. baumannii can evolve quickly, sometimes changing within a single hospital outbreak or even within an individual. They found that sharing of resistance genes between bacteria—a concept known as"horizontal gene transfer"—occurs frequently.
"We used to think, 'you treat this bacteria with this drug,' but now we know that you have to look more carefully not just at the bacteria but at each one’s genetic characteristics," says Adams.
"Our study painted a very unique picture of A. baumannii and its various strategies for acquiring resistance," Bonomo points out."The genetic elements were arranged in such a way that the organism became uniquely adaptable to life in a hospital and also to life in patients." While describing the completed study as the"tip of the iceberg" in understanding A. baumannii resistance genes, Bonomo says the research points the way to screening tools that could identify DNA sequences linked with drug resistance, and ultimately to therapies that could circumvent them. Building on the completed study, Bonomo looks forward to garnering a bigger picture with Acinetobacter strains gathered from hospitals around the world.
For now, the medical community must rely on infection control procedures to stem the spread A. baumannii—an exceptionally hardy bug that can survive for days on hospital curtains, door handles, medical equipment, and other surfaces. Steps to block its spread are similar to prevention methods for other infections—for example, hand-washing, the use of gowns and gloves, and isolation of infected patients.
This article originally appeared in the March 2009 issue of VA Research Currents.