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The search for new antibiotics

Monday, August 18 08:27:07

Pampering leafcutter ants with fragrant rose petals and fresh oranges may seem an unlikely way to rescue modern medicine, but scientists at a lab in eastern England think it's well worth trying.

As the world cries out for new antibiotics, researchers at the John Innes Centre (JIC) in Norwich are also taking a bet on bacteria extracted from the stomachs of giant stick insects and cinnabar caterpillars with a taste for highly toxic plants.

Their work is part of a new way of thinking in the search for superbug-killing drugs - turning back to nature in the hope that places as extreme as insects' insides, the depths of the oceans, or the driest of deserts may throw up chemical novelties and lead to new drugs.

"Natural products fell out of favour in the pharmaceutical sphere, but now is the time to look again," says Mervyn Bibb, a professor of molecular microbiology at JIC who collaborates with many other geneticists and chemists. "We need to think ecologically, which traditionally people haven't been doing."

The quest is urgent. Africa provides a glimpse of what the world looks like when the drugs we rely on to fight disease and prevent infections after operations stop working.

In South Africa, patients with tuberculosis that has developed resistance to all known antibiotics are already simply sent home to die, while West Africa's Ebola outbreak shows what can happen when there are no medicines to fight a deadly infection - in this case due to a virus rather than bacteria.

Scant financial rewards and lack of progress with conventional drug discovery have prompted many Big Pharma companies to abandon the search for new bacteria-fighting medicines. Yet for academic microbiologists these are exciting times in antibiotic research - thanks to a push into extreme environments and advances in genomics.

"It's a good time to be researching antibiotics because there are a lot of new avenues to explore," said Christophe Corre, a Royal Society research fellow in the department of chemistry at the University of Warwick.

Marcel Jaspars, a professor of organic chemistry at Britain's University of Aberdeen, is leading a dive deep into the unknown to search for bacteria that have, quite literally, never before seen the light of day.

With 9.5 million euros of European Union funding, Jaspars launched a project called PharmaSea in which he and a team of international researchers will haul samples of mud and sediment from deep sea trenches in the Pacific Ocean, the Arctic waters around Norway, and then the Antarctic.

Like the guts of stick insects or the protective coats of leafcutter ants, such hard-to-reach places house endemic populations of microbes that have developed unique ways to deal with the stresses of life, including attacks from rival bugs.

"Essentially, we're looking for isolated populations of organisms. They will have evolved differently and therefore hopefully produce new chemistry," Jaspars explains.

Nature has historically served humankind well when it comes to new medicines. Even Hippocrates, known as the father of Western medicine, left historical records describing the use of powder made from willow bark to help relieve pain and fever.

Those same plant extracts were later developed to make aspirin - a wonder drug that has since been found also to prevent blood clots and protect against cancer.

Pfizer's Rapamune, used to prevent rejection in organ transplantation, came from a micro-organism isolated from soil collected in Easter Island in the Pacific Ocean, and penicillin, the first ever antibiotic, comes from a fungus.

Cubicin, an injectable antibiotic sold by U.S.-based Cubist , was first isolated from a microbe found in soil collected on Mount Ararat in eastern Turkey.

In all, more than half of all medicines used today were inspired by or derived from bacteria, animals or plants.

Yet as Jaspars says: "It's not just about going to extreme locations, it's now also about using smart techniques."

Modern gene-sequencing machines mean it is now possible to read microbial DNA quickly and cheaply, opening up a new era of "genome mining", which has reignited interest in seeking drug leads in the natural world.

It marks a significant change. In recent decades drug developers have focused on screening vast libraries of synthetic chemical compounds in the hope of finding ones capable of killing bad bugs. Such synthetic analogues are easier to make and control than chemicals from the wild, but they have yielded few effective new drugs. (Reuters)

For more visit: www.businessworld.ie