Novel class of antibiotics discovered

Novel class of antibiotics discovered

- Candidate antibiotic inhibits bacterial enzyme needed for growth. - Novel class destroys MRSA. - New strategy developed for screenin

GALAPAGOS N.V. recently announced that it has discovered an entirely new class of antibiotics that shows strong activity against all tested drug-resistant strains of Staphylococcus aureus.

Bacterial infections that have become resistant to all existing antibiotics pose a pressing health care problem because treatment options for patients become very limited. Methicillin-resistant S. aureus (MRSA) is the best-known example, causing a potentially life-threatening infection that occurs most frequently among hospital patients.

This newly discovered Galapagos candidate antibiotic works by inhibiting the target DNA pol III-alpha, an enzyme present in all bacteria that is essential for their growth; this target is absent in people. The novel mode of action -- inhibition of DNA pol III-alpha -- may be used to explore a variety of novel antibiotics, targeting bacteria that have developed resistance to current antibiotics.

Using this novel target, Galapagos has selected a first candidate antibiotic, CAM-1, to enter drug development. CAM-1 was tested against more than 250 different bacterial strains and effectively killed 100% of all drug-resistant S. aureus, including MRSA, Galapagos said. CAM-1 shows better efficacy than standard antibiotics, as shown by in vivo bacterial infection models.

Galapagos aims to enter clinical trials in the first quarter of 2014, with a proof-of-concept study conducted thereafter. This novel antibiotic program, including all compounds targeting MRSA, is fully proprietary to Galapagos.

Galapagos is a midsize, clinical-stage biotechnology company that specializes in the discovery and development of small-molecule and antibody therapies with novel modes of action. Its headquarters are in Mechelen, Belgium.


New antibiotics

Researchers at the University of California-Santa Cruz (UCSC) have developed a new strategy for finding novel antibiotic compounds using a diagnostic panel of bacterial strains to screen chemical extracts from natural sources.

UCSC noted that most of the currently available antibiotics are derived from natural compounds produced by microorganisms such as bacteria and fungi, and new antibiotics that drug companies develop are often synthetically tailored variations of existing classes of antibiotics.

To combat the problem of antibiotic resistance, however, researchers want to find antibiotics with completely novel structures and modes of action.

The new screening procedure, called BioMAP (antibiotic mode-of-action profile), promises to streamline the discovery of new antibiotics from natural sources by providing a low-cost, high-throughput platform for identifying compounds with novel antibiotic properties, UCSC said.

"If you take a library of natural product extracts and screen them against a bacterial target, you will find a lot of antibacterial compounds, but almost all of them will be known structures," said Roger Linington, UCSC assistant professor of chemistry and biochemistry. "BioMAP is a new way to look at antibiotic activity so that you're not wasting time and energy chasing things that turn out to be well-studied compounds of little therapeutic value."

Linington's laboratory group focused on marine natural products -- mostly microorganisms isolated from marine sediments -- as a source of lead compounds for drug discovery. The BioMAP project was led by Weng Ruh Wong, who was first author of a paper presenting the BioMAP screening procedure published in the Nov. 21 issue of Chemistry & Biology.

It makes sense to look for antibiotics in environments where bacteria compete with one another, Linington said. About 80% of currently available antibiotics are derived from natural products, mostly from soil microorganisms. However, because natural products have been studied so extensively, the rate of return in terms of novel chemistry has decreased precipitously.

"Almost all of the new antibiotics are 'me too' drugs that work in the same way as an existing drug," Linington said. "The paucity of new therapeutic options for bacterial infections is a well-recognized and ongoing issue, and it is a major emerging threat to public health, both nationally and on a global scale," he said.

Volume:84 Issue:51

Hide comments


  • Allowed HTML tags: <em> <strong> <blockquote> <br> <p>

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.