Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
San Francisco Chronicle - Thursday, August 13, 1992
In the near future, it should also lead to new tests to quickly identify cases of drug-resistant tuberculosis. Current tests take months, and in the meantime patients receive ineffective treatment and remain contagious.
The researchers reported in yesterday's issue of the journal Nature that strains of the tuberculosis bacterium that are resistant to the drug isoniazid, the mainstay of tuberculosis treatment, had lost a single large gene.
When the scientists reinserted the missing gene in the laboratory, the bacterium once again became vulnerable to the drug.
The research strongly suggests that resistance to the drug is related to a missing or defective copy of the gene.
The paper is the first fruit of a new wave of research on tuberculosis prompted by the disease's recent resurgence. Tuberculosis resistant to isoniazid -- and sometimes other drugs -- has become a major problem in many American cities, particularly in hospitals and among people who are infected with HIV, the virus that causes AIDS.
At some hospitals in New York, more than 30 percent of new tuberculosis cases have some drug resistance.
The discovery comes at a time when more and more strains of tuberculosis have become insensitive to isoniazid, leading to fatal outbreaks in this country and a rise in the death rate from tuberculosis abroad.
Although tuberculosis that responds to isoniazid is reliably cured, resistant strains must often be treated with four to seven drugs. Half the people who get active cases of drug-resistant tuberculosis die. Although there are other drugs to treat tuberculosis, they generally are less effective, more expensive and have more side effects than isoniazid.
By understanding how tuberculosis develops resistance to the drug, it might be possible to modify the drug to overcome it, said Dr. Stewart Cole of the Pasteur Institute in Paris, the main author of the Nature paper. He conducted the research in collaboration with Dr. Ying Zhang of Hammersmith Hospital in London.
Also, because the new advance identifies a gene whose absence makes the bacterium drug resistant, it should be relatively simple to develop biochemical probes to find the gene, which could determine in a matter of hours whether a patient's sputum contains drug-resistant tuberculosis.
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