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
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,
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.