Biomedical scientists collaborating on translational research at two Buffalo institutions are reporting the discovery of a novel, and heretofore unrecognized, set of genes essential for the growth of potentially lethal, drug-resistant bacteria. The study not only reveals multiple, new drug targets for this human infection, it also suggests that the typical methods of studying bacteria in rich laboratory media may not be the best way to identify much-needed antimicrobial drug targets.
The paper (http://mbio.asm.org/content/3/4/e00113-12) focuses on a Gram-negative bacteria called A. baumannii. It is published in the current issue of mBio, as an 'editor's choice' paper. The findings may be relevant to other Gram-negative bacteria as well. (A graphic related to the research is at http://www.buffalo.edu/news/13673.)
A. baumannii is responsible for a growing number of hospital-acquired infections around the world. It can be fatal to patients with serious illnesses, the elderly and those who have had surgeries. Infections also have been seen in soldiers returning from Iraq and Afghanistan with battlefield injuries.
"Generally, healthy people don't get infected," explains lead author Timothy C. Umland, PhD, research scientist at Hauptman-Woodward Medical
Research Institute (HWI) and professor of structural biology in the University at Buffalo School of Medicine and Biomedical Sciences. "But 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 healthcare-associated infections."
Typically, the way that essential genes for microbial pathogens are found is by growing the bacteria under optimal conditions, says co-author Thomas A. Russo, MD, professor in the UB departments of medicine and microbiology and immunology. Genes found to be essential for growth are then entered into the Database of Essential Genes (DEG), which contains genes considered essential for the sustenance of each organism.
The researchers at HWI and UB decided to try to better understand what A. baumannii needs in order to grow when infecting patients.
"Laboratory conditions create a different type of environment from what happens in patients," Umland says, "where certain nutrients the bacteria need will be 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."