Ironing out new details of tuberculosis infection

Scientists in India, led by a Howard Hughes Medical Institute (HHMI) international research scholar, have identified five key genes that enable Mycobacterium tuberculosis to acquire the iron it needs to sustain growth and promote infection.

"Targeting genes within this cluster represents a good strategy for preventing tuberculosis and other mycobacterial infections," said Rajesh S. Gokhale, an HHMI international research scholar at the National Institute of Immunology in New Delhi, India, and lead investigator on the study. "Because some of these genes are conserved across a number of related bacterial families, they are promising targets for drugs to treat TB and other bacterial diseases."

The tuberculosis bacterium, which infects more than one third of the world's inhabitants, is a leading cause of death and disease worldwide.

Gokhale and colleagues report their findings in early online publication January 30, 2006, in the Proceedings of the National Academy of Sciences.

When M. tuberculosis infects humans, it takes up residence in immune cells called macrophages. To survive in this harsh environment, mycobacteria, like many other types of bacteria, need iron to carry out life-sustaining functions, such as creating proteins and synthesizing nucleotides to form DNA. However, free iron is not easily found in an intracellular environment. To obtain this rare element, most bacteria manufacture and secrete chemical compounds called siderophores that scavenge iron from the environment.

Researchers discovered siderophores--chemical compounds used by bacteria to scavenge iron from their cellular environment--well over 50 years ago, but the genes involved in adding the long-chain lipid anchor that enables M. tuberculosis to do so more efficiently, remained a mystery until now.

Mycobacteria have evolved siderophores with lipid-chain tails that enable them to exploit the macrophage's lipid-trafficking system to capture iro

Contact: Cindy Fox Aisen
Howard Hughes Medical Institute

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