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Drug-resistant tuberculosis reversed in lab

Christian Fernsby ▼ | June 5, 2019
Researchers at Washington University School of Medicine in St. Louis and Umea University in Sweden have found a compound that prevents and even reverses resistance to isoniazid, the most widely used antibiotic for treating tuberculosis.
Medicine   Tuberculosis
The research was conducted in bacteria growing in the lab, setting the stage for future studies in animals and people.

Using the compound in conjunction with isoniazid potentially could restore the antibiotic's effectiveness in people with drug-resistant tuberculosis.

The compound also may bolster the antibiotic's power to kill TB bacteria even those sensitive to drugs.

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis.

Once inside the body, the bacteria morph into a tougher form that can withstand more stress and is harder to kill.

Rather than look for new and better antibiotics, Stallings and co-first authors Kelly Flentie, PhD, a former postdoctoral researcher at Washington University, and Gregory Harrison, a graduate student, decided to look for compounds that prevent the bacteria from toughening up.

When put in a low-oxygen environment to mimic the stressful conditions TB bacteria encounter inside the body, the bacteria come together and form a thin film called a biofilm that is resilient to not only low-oxygen conditions but also to antibiotics and other stressors.

With the help of co-senior author Fredrik Almqvist, PhD, a professor of chemistry at Umea University, they screened 91 compounds that share a core chemical structure that inhibits biofilms in other bacterial species.

The researchers found one compound, called C10, that did not kill the TB bacteria but prevented them from forming a biofilm.

Further experiments showed that blocking biofilm formation with C10 made the bacteria easier to kill with antibiotics and even curbed the development of antibiotic resistance.

The researchers needed only a fraction of the amount of isoniazid to kill the TB bacteria when C10 was included than with isoniazid alone.

In addition, one out of 1 million TB bacteria spontaneously become resistant to isoniazid when grown under typical laboratory conditions.

But when the researchers grew TB bacteria with isoniazid and the compound, the drug-resistant mutant bacteria never arose.