Reversing Antibiotic Tolerance

Reversing Antibiotic Tolerance

Antibiotic tolerance occurs when bacteria are able to survive in the presence of antibiotics. This is dangerous because tolerant bacteria can cause infections that persist even after treatment.

Some bacteria are tolerant to beta lactam antibiotics such as penicillin. Drugs in this class kill bacteria by breaking down their cell walls. Until now, how tolerant bacteria survive this process was poorly understood.

A recent study in mice showed that when tolerant bacteria were exposed to beta lactam antibiotics and the cell wall was destroyed, a damage repair response system called VxrAB was activated. This led researchers to develop a mutant bacterial strain that lacked VxrAB.

When the mutant bacterial cell walls were damaged by beta lactam antibiotics, the transfer of electrons was misdirected. This caused hydrogen peroxide to accumulate in the cell, changing the oxidation state of iron. As a result, the signals that allow a cell to gauge how much iron it has were disrupted. Without the ability to sense iron levels, the mutant bacteria behaved as if they were iron starved and continually acquired iron, leading to iron toxicity and cell death.

These findings suggest that new drugs could be developed to exploit oxidative damage and iron influx, reversing tolerance and making the bacteria susceptible to treatment with antibiotics.

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