The Tuberculosis (tb) bacteria kill two people every three minutes. The bacteria uses iron from the human body to survive. But the mechanism by which they source the iron was not known. Researchers from the University of Hyderabad have recently cracked the mechanism. Their research paves the way for new medicines to treat the disease better.

The tb pathogen sources its iron through molecules called siderophores, which have high affinity for iron. First, the pathogens release these molecules, which extracts iron from human cells, leaving them iron-scarce. The molecules are then transported back to the pathogen, which synthesizes the iron to sustain and grow at the cost of the host. These actions are dependent on two proteins that help complete the transportation cycle of siderophores. Blocking this transportation through medicines can be a breakthrough to cure tb. First, it will stop the iron uptake and secretion. Since there will be no export pathway for siderophores, it will extract iron from the microbe itself.

“A proper pool of iron needs to be maintained because low or even high concentration of iron is harmful to the cell,”

says Aisha Farhana, the lead author of the study published in the May 7 issue of PLoS One. The other concern, she says, is that anaemia is often an offshoot of tb. This is because iron is a major component of blood.

According to K K Chopra of the New Delhi Tuberculosis Centre,

“Till now, the anti- tb drugs that we have been using target protein uptake, not iron uptake. If developed and compared with a placebo, the drug might be more effective than the currently available drugs.”

Treatment at present involves a combination of drugs introduced in India in 1997, according to who recommendations. Also, who surveys in 1997 and 2007 found that multi-drug resistance tb strains were present in 63 of the 72 countries surveyed.

The study noted that transferring, a protein that transports iron from the blood to the brain, may not be doing its job well. That may lead to exposure of other cells to iron, and their subsequent degeneration and the diseases. The protein binds iron on to its surface. It then curls around the iron and seals it. This prevents the iron from getting exposed to other cells till it reaches its destination organ—the brain.

In the experiment, transferring was placed on an open surface and observed over a period of time.

“We simulated conditions for ageing so that the existing molecules interacted with each other. We found the molecules self-assembled into fibres and iron that was earlier wrapped inside the protein started settling in bands along the length of the fibre,’

says Sandeep Verma of the Department of Chemistry, IIT, Kanpur. “Iron when exposed to molecular oxygen, leads to degeneration of cells,’ says Verma. The study was published in Angewandte Chemie (Vol 9999, No 2008). Although the researchers say exposure of brain cells to iron leads to the diseases, they say there is no clear reason for the exposure.

“Dehydration may be responsible for it. There are restricted membranes where water does not go easily or has been removed from the vicinity of the protein, resulting in the protein malfunction,’ says Verma.

However, their experiment is not foolproof because the biological environment is more complicated. Experiments need to be conducted in that medium. “Definitive proof will come only from clinicians who can slice out a part of the brain and test for iron deposition,’ he added.

The researchers, Michael Worobey and team from the University of Arizona, say the finding will help in the development of an efficient vaccine against aids. The researchers say they studied blood samples of five patients who were among the first recognized aids victims; all of whom had immigrated to the us. They compared the samples with those of another 117 aids patients from different parts of the world and traced back the family history of the virus. The study appeared online on October 30, 2007 in the journal Proceedings of the National Academy of Sciences.

But many experts say the results might not be useful in developing a vaccine against the deadly virus. So far, an effective vaccine has been elusive as the character of the virus changes frequently from place to place.

“There are eight major subtype of HIV-1 in addition to the existing recombinants within the subtype which are accumulating and these type of changes are increasingly occurring as days progress which poses a great challenge to vaccine development” says Smarajit Jana, member of the National Aids Council in Delhi.

He says, “When an epidemic spreads, it goes to 3-4 different directions, not just to one area. So, a lot more archival samples have to be tested to get the truth.’ In India, the major circulating stain is the subtype C and scientists say the vaccine developed on the strain collected from one country may not be effective in other countries because of the very nature of the virus which is not predictable and changes rapidly.

Meanwhile, the report has sparked off a controversy outside the us . Haitians see it as a ploy to vilify the country. “This report is just an extension of a larger campaign by the us to squash the people’s movement in Haiti,’ said Noluthando Williams, a Haitian activist.