Mouse Study Could Help Fight TB in Humans

(CN) — A class of drugs developed to treat cancer and other diseases enhances antibiotic treatment of tuberculosis in mice, a new study finds.

The report published Thursday in PLOS Pathogens describes the effectiveness of matrix metalloproteinase (MMP) inhibitors when combined with antibiotics that attack Mycobacterium tuberculosis, the bacterium responsible for tuberculosis.

While there are effective anti-tuberculosis drugs, patients must take them for six to nine months, and the challenge of maintaining treatment during that period can lead to the emergence of drug-resistant strains of M. tuberculosis.

Shortening the treatment period could reduce drug resistance and save lives, and previous research has suggested that incorporating MMP inhibitors could enhance the power of standard tuberculosis antibiotics — though the results of doing so have been mixed.

To evaluate the potential of MMP inhibitors, researchers systematically tested them in mice infected with M. tuberculosis. The bacterium produces significant changes to host tissue at the site of infection — typically in the lungs. It also triggers the formation of protective structures in the immune system known as granulomas, and induces leaks in nearby blood vessels.

The team found that MMP inhibitors, which stop the actions of MMP enzymes that break down connective tissue, improved blood vessel health at the site of infection in mice. This led to better delivery and retention of the tuberculosis drugs rifampicin and isoniazid at granulomas, greatly enhancing the number of bacteria they killed.

The safety of MMP inhibitors has already been tested in humans. The drugs are also fairly cheap, making them an appealing option for limiting the duration of tuberculosis treatment.

More research is needed to learn whether the results seen in mice will occur in humans.

“The lung forms granulomas to contain the TB infection, but ironically the granulomas also provide TB bacteria shelters from immune surveillance and antibiotics treatment,” the team wrote. “The MMP inhibitors restore blood vessels in the infectious site, which provide a conduit for antibiotics to reach and kill the bacteria.

“This synergy will revitalize current TB treatment and reduce the risk of multi-drug resistant strains.”

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