Tuberculosis bacteria live inside one-third of the human population, but are especially threatening to people who suffer from poverty, malnutrition and such infectious diseases as AIDS. To make matters worse, drug-resistant tuberculosis strains have now emerged, and no significant new drugs are in production.
Cornell microbiologist David Russell was recently given more than $600,000 in federal stimulus funds as he races to better understand how the bacterium, Mycobacterium tuberculosis, survives inside human cells and feeds off of lipids. By better understanding the bacterium's physiology, Russell -- professor and chair of the Department of Microbiology and Immunology in the College of Veterinary Medicine -- hopes to develop therapies that use biological pathways to kill the pernicious bug.
The funds to Russell from the American Recovery and Reinvestment Act (ARRA) are administered through the National Institutes of Health. They include $95,900, which Russell has already used to buy American-made equipment for specialized screening to identify new drugs for treating tuberculosis. Another two-year grant of $530,882 has allowed Russell to hire two postdoctoral researchers and a graduate student to research the cell biology of enclosed compartments or vacuoles that the bacterium forms inside white blood cells (called macrophages), which engulf M. tubercolosis as part of the body's immune response.
Russell is trying to determine whether conditions in these vacuoles are hostile or benign to the bug, and "how the bacterium exploits the vacuole to get its nutrients and how it manipulates the host cell to sustain the infection," he said.
Early findings suggest that the compartments contain enzymes that generate fatty acids, glycerol and cholesterol, "all excellent carbon sources" for M. tuberculosis , Russell said.
His lab researchers also have developed a range of real-time readouts from inside the vacuoles to measure such parameters as pH and 10 different enzymatic activities to test whether the bacterium is under stress by the bacterium.
"Once the bug has re-engineered the compartment, it is not under a great deal of stress," he said.
To date, Cornell has received 120 ARRA grants, totaling almost $99 million over two years.