Published October 15, 2012
Biomedical researchers have discovered a novel, previously
unrecognized set of genes essential for the growth of potentially
lethal drug-resistant bacteria.
Their study reveals multiple new drug targets for this infection and suggests that typical methods of studying bacteria in rich laboratory media may not be the best way to identify antimicrobial drug targets.
During the study, researchers tried to better understand what A. baumannii—a bacteria responsible for a rising number of hospital-acquired infections—needs in order to grow when infecting people.
Typically, scientists find the essential genes for microbial
pathogens by growing the bacteria under optimal conditions,
explains study co-author Thomas
A. Russo, MD, professor of medicine and
However, laboratory conditions create a different type of environment than the human body, where certain nutrients the bacteria need are present in very low amounts, and where the bacteria encounter immune and inflammatory responses.
“We were purposely trying to test for genes that are
important for growth in these more realistic environments,”
explains lead author Timothy C. Umland, PhD, professor of structural
biology and a research scientist at Hauptman-Woodward Medical
The team performed genetic screening to identify bacterial genes required for the growth and survival of A. baumannii in human ascites, a peritoneal fluid present under a variety of pathologic conditions.
“We found that nearly all of these 18 genes had not been
identified as essential in the Database of Essential
Genes”—the record of genes considered indispensable to
support cellular life—“because they weren't necessary
for growth in an ideal laboratory environment,” Russo
“This is a large set of genes that has been flying under the radar.”
A. baumannii doesn’t generally infect healthy people, but
it can be fatal to patients with serious illnesses, those who have
had surgeries and the elderly. Soldiers returning from Iraq and
Afghanistan with battlefield injuries also risk infection.
“What's challenging about A. baumannii is that it can survive in the hospital environment and is very hard to eradicate with common disinfectants, leading to health care-associated infections,” Umland says.
Many strains are resistant to nearly all anti-microbial drugs
and some strains are resistant to all of them, Russo notes.
Currently, there are no new agents being tested for human use that
are active against the bacteria, he adds.
The newly identified genes suggest new, high-value drug targets
for A. baumannii infections and may be relevant to other
“So far, our computational models show that these genes seem to be conserved across Gram-negative infections, meaning they may lead to new drugs that would be effective for other drug-resistant infections as well,” Umland explains.
The researchers are now pursuing antibacterial drug discovery efforts focused on the newly identified bacterial targets.
The research was funded by grants from the Telemedicine and Advance Technical Research Center of the U.S. Army Medical Research and Materiel Command, an interdisciplinary grant from UB and a VA Merit Review grant from the U.S. Department of Veterans Affairs.
Other co-authors on the paper are L. Wayne Schultz, PhD, of the Department of Structural Biology, and Ulrike MacDonald, Janet M. Beanan and Ruth Olson of the Departments of Medicine, Microbiology and Immunology, and UB’s Witebsky Center for Microbial Pathogenesis.