Today’s advance online publication of Nature includes a report showcasing a new kind of antibacterial agent that could be effective against a broad range of drug-resistant bacteria.

The agent belongs to a new class of drugs called novel bacterial topoisomerase inhibitors (NBTIs). They target certain enzymes used by the bacteria to regulate the replication of their DNA.

The paper describes how researchers target a topoisomerase called DNA gyrase using a specific NBTI called GSK299423. When the inhibitor binds to the enzyme, it forms a molecular complex with the bacterial DNA, effectively clamping down on the whole operation. Unable to continue with genetic replication, the bacteria are unable to reproduce or function properly, and die quickly — in test tubes, it’s a matter of hours.

The GlaxoSmithKline scientists who developed the agent tested it primarily against Staphylococcus aureus. In recent years S. aureus has developed resistance to a number of antibiotics, including quinolones, which are thought to also target topoisomerases (albeit at a completely different site).

David Payne, vice president of GSK’s antibacterial discovery unit, says there’s reason to believe NBTIs will be effective against many other kinds of bacteria, including the notoriously resistant S. aureus strain MRSA.

“The target is there, and it’s extremely well conserved among bacteria. We just have to make a molecule to penetrate all those different pathogens,” Payne says. He estimates GSK will have an NBTI candidate in human trials in about 12-18 months.

Below, we’ve got accompanying video from the authors showing a schematic representation of the NBTI mechanism in action. The antibacterial is shown in yellow, and the bacterial DNA is shown in green.

Video and image courtesy Ben Bax.