GLOBAL: Combating multi-resistant bacteria

An international quest launched by the Infectious Diseases Society of America to produce 10 antibiotics to combat multi-resistant bacteria by 2020, has taken a step towards the goal with the recreation of the DNA of an ancestral wallaby gene from 60 million years year ago.

In a paper published in the journal PLoSONE, an Australian team reports that recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials.

"Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments.

"While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young," the team writes in the journal.

The researchers decided to take a new approach by exploring the 'lower reaches' of the tree of life to find a suitable candidate in the hope of developing a super-antibiotic - one that may be up to 10 times more potent against multi-drug-resistant bacteria than tetracycline and ampicillin, according to initial laboratory tests.

After searching the genome of the tammar wallaby, the scientists identified genes that code for 14 peptides, part of the animal's innate immune system. These help protect its extremely tiny and vulnerable newborn against infection while they are in the pouch.

Wallaby pouches harbour many bacteria similar to the superbugs that affect humans in hospitals. Then, using bio-computational modelling, they worked backwards to recreate the original ancestral marsupial gene that codes for these peptides.

"There's a possibility these ancient peptides could be developed as intravenous treatment for people who have infections that are resistant to available antibiotics," said Dr Ben Cocks, professor of animal genetics and genomics at Melbourne's La Trobe University.

Cocks said another application for which such a 'new' chemical showed promise was mastitis, a big problem for the global dairy industry where it costs billions of dollars in losses every year - including a staggering US$1.8 billion in America.

His team has also identified eight candidate genes in platypus. "Marsupial and monotreme young are protected by antimicrobial peptides that are potent, broad spectrum and salt resistant. Hence the genomes of our distant relatives may hold the key for the development of novel drugs to combat multidrug-resistant pathogens," he said.