TB breakthrough
Two female scientists from Africa have made a significant breakthrough in
the treatment of the worldwide killer tuberculosis. Research done by South
Africa's Molecular Mycobacteriology Research Unit at the University of the
Witwatersrand in Johannesburg could save millions of lives worldwide.
Award-winning scientist Dr Valerie Mizrahi, who heads the research unit,
falling under the Medical Research Council, the National Health Laboratory
service and Wits University, together with her colleagues, have identified a
protein that may be involved in the survival of the organism that makes the
Tuberculosis bacilli resistant to drugs.
TB is a devastating, infectious disease that causes about two million
deaths annually. It is caused by the bacterium Mycobacterium tuberculosis. Drug resistant strains
of Mycobacterium tuberculosis have started to show up in areas where TB was no
longer considered a public health risk, spurring
research into how this organism is able to develop drug resistance.
Together with fellow South African Dr Helena Boshoff, now doing
post-doctoral work at the National Institutes of Health (NIH) laboratories
in the United States, and American Dr Clifton Barry from the NIH, the team's
work is a featured article in the prestigious journal Cell.
Mizrahi and her colleagues examined a protein called DnaE2 that is present
in some bacteria but has no known role. DnaE2 belongs to the class of
proteins known as DNA polymerases that copy DNA. At first glance, DnaE2
looks a lot like well-known polymerases that copy DNA with a high degree of
accuracy. But it is different, in very important ways.
If you expose the bacterium to DNA damaging stimuli, like hefty doses of
ultraviolet light, this results in two things happening as the bacterium
fights off the damage: it pumps out elevated levels of DnaE2 and this
stimulates the formation of bacterial mutants that are resistant to certain
drugs used to treat TB. The link between these two was confirmed by animal
tests: deleting the dnaE2 gene from M. tuberculosis not only eliminated the
drug-resistant mutants but also reduced the ability of M. tuberculosis to kill
infected mice.
By looking at the types of mutations induced by DnaE2 the
scientists realised that it copies DNA with surprisingly low accuracy and this
"sloppiness" allows for slightly new forms of the bacteria to emerge.
When exposed to drugs, mutants that are resistant survive better than other
forms of the bacteria and they proliferate, accounting for how resistance can
occur in a previously drug-sensitive infection.
The researchers concluded that DnaE2 plays a key role in the survival and
proliferation of M. tuberculosis, contributing to the ability of the
bacteria to take on forms that are resistant to previously effective drugs.
According to Dr. Mizrahi, "DnaE2 provides a new potential target for
reducing the rate of emergence of certain types of drug resistant strains of
M. tuberculosis."
For more information:
Contact Dr Valerie Mizrahi on 011 489 9370 or e-mail
mizrahiv@pathology.wits.ac.za
Information on TB in South Africa visit: http://www.sahealthinfo.org/
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