Hopes that new antibiotic will fight drug-resistant bacteria

A new antibiotic weapon could help win the war against drug-resistant bacteria responsible for a host of diseases, scientists hope.

The bug destroyer targets an enzyme, LpxC, that is vital to the structure of gram-negative bacteria, a huge microbial family posing one of the biggest threats to human health.

Gram-negative bacteria, characterised by a toxic outer membrane, cause a large number of infections ranging from bubonic plague to peritonitis, cholera, and E.coli food poisoning.

The new drug, code-named LPC-069, is the first shown to suppress the gram-negative enzyme at safe doses. Its development could pave the way to novel treatments for a wide range of multi-drug resistant infections.

Lead scientist Dr Pei Zhou, from Duke University in North Carolina, US, said: "Our study shows that LpxC is a viable target, and we can dose the compound at very high levels without noticeable toxicity."

Biologists first suggested targeting LpxC more than 20 years ago, but it proved impossible to find a drug compound that was safe at effective dosage levels.

The new antibiotic was tested on mice infected with the plague bug Yersinia pestis.

Five days after being injected with the bacteria, the animals remained alive and apparently healthy. A comparison group of untreated infected mice all died within the same time period.

After two weeks there was no sign of plague bacteria invading the organs of the treated mice, indicating that the infection had been cleared away.

Laboratory tests showed that the drug was active against more than a dozen types of harmful bacteria cultured from human patients, including multi-drug resistant strains.

Experiments with another LpxC inhibitor proved less successful because it produced side effects including white blood cell accumulation in the lungs and intestines, and liver toxicity.

LPC-069 caused no serious side effects even at the highest tested doses, said the researchers writing in the journal mBio.

The enzyme is one of six proteins that are vital for the formation of the outer membranes of gram-negative bacteria.

Other members of the enzyme group may also offer valuable targets for new antibiotic treatments, the researchers believe.

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