Indiscriminate use of antibiotics has led to the development of many bacterial strains which show antibiotic resistance and are called ‘super bugs’. One such bacteria, the Methicillin-resistant Staphylococcus aureus, commonly known as MRSA, is a major cause of hospital-acquired infections, and the second biggest cause of death by drug-resistant bacteria in the US. These bacteria are resistant to the most widely used class of antibiotics, called beta-lactams, which include penicillin, methicillin and carbapenems.
These antibiotics work mainly by targeting essential components of the cell wall of the bacteria. But the MRSA protects itself by producing a type of molecule that can soak up the antibiotic and prevent it from working.
However, now a team of researchers from the Merck Research Laboratories in New Jersey lead by Christopher Tan have found a way to overcome the drug resistance of the superbug. They have identified two compounds that could work and make the bacteria susceptible to beta-lactam antibiotics again.
These two compounds called tarocin A and tarocin B cannot directly kill the bacteria but they act on part of the cell wall of the bacterial membrane known as techoic acid and make them more susceptible to the antibiotics. Thus either one of the compounds need to be administered along with the antibiotics. The combination has shown to kill MRSA in both clinical samples and in infected mice. The compounds haven’t yet been tested in humans.
“It’s like a two-prong attack,” says David Brown, of the charity Antibiotic Research UK. “They’re weakening the wall by a second mechanism, which makes it easier for the beta-lactams to have their effect as well.”
However, the researchers suspect that this combination alone would not be effective in the long run as the bacteria would become eventually resistant to it. To get around this, Tan suggests adding a third drug that targets another part of teichoic acid production. “We think by having a deep understanding of the biology of this particular pathway, it enables us to identify where the weak spots are in the bacterium to address resistance,” he says.
The global antibiotic resistance crisis can circumvented by using combination drugs to thwart antibiotic resistance.
Brown’s charity is funding a screening programme to see if any existing compounds also work as antibiotic resistance breakers.
“It will take 20 years minimum to come up with a reasonable number of new antibiotics,” says Brown. “So we’ve got to salvage our current antibiotics over the next 20 years or so with resistance breakers, which are really the only chance we’ve got.”
The original paper can be accessed here.