Lynn Connolly, MD, PhD
For many decades, doctors have cured tuberculosis by prescribing powerful antibiotics. These medications interfere with the ability of the TB bacteria to grow and divide, and eliminate infections in most cases. But they take a long time to work, requiring patients to faithfully swallow multiple pills over six months or more.
Now a team of researchers led by Lalita Ramakrishnan, MBBS, PhD, of the University of Washington, and Lynn Connolly, UCSF assistant adjunct professor of medicine, MD, PhD, has discovered that one of the reasons TB treatments take so long is because the bacteria actively fight back against the antibiotics. Their work, published this week in the journal Cell, has the potential to dramatically reduce the time it takes to cure TB.
Tuberculosis (TB) is a disease caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine, and brain. If not treated properly, TB disease can be fatal.
Scientists have always assumed treatment was slow because some of the bacteria in a patient’s body were “resting” in a dormant state, explained Connolly, who was involved in the research as a postdoctoral fellow at the University of Washington. Because antibiotics are most effective at killing rapidly growing bacteria, these dormant bacteria were thought to be impervious to antibiotic therapy.
Instead, the researchers found, the bacteria are actively fighting back against the antibiotics using molecular machines called “efflux pumps,” which force the drugs out of the bacteria before they can do their work. The TB bacteria already use these pumps during the natural course of infection, perhaps to pump out antibacterial compounds produced as the immune system tries to fight off the illness.
Drugs already on the market are able to counter this defense mechanism, Connolly said. One is the calcium channel blocker verapamil, approved by the US Food and Drug Administration for treating conditions like high blood pressure and angina. The availability of this and similar inexpensive drugs should give scientists a way to quickly test whether they can be combined with traditional antibiotic regimens to speed up treatment for tuberculosis, she said.
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Read the article in Cell