Discovery of compound that renders the MRSA superbug vulnerable to antibiotics

Oct 13 2004

A UK company claims to have discovered a compound that renders the MRSA superbug vulnerable to the antibiotic it normally resists.

MRSA- methicillin-resistant Staphylococcus aureus- is defined by its ability to resist the antibiotic methicillin. Like penicillin, methicillin works by blocking bacterial enzymes called PBPs, which normally strengthen cell walls by forming cross links.

The first MRSA strains appeared in 1961, just two years after methicillin was launched. These bacteria got their resistance by picking up the gene for another PBP enzyme, PBP2a, to which methicillin cannot bind. MRSA strains now cause up to 60 per cent of all staph infections in some hospitals. Some MRSA strains are also becoming resistant to other antibiotics- including vancomycin, the antibiotic doctors resort to when nothing else works. But Michael Levey's team at Pharmaceutica in Worcestershire, UK, may have discovered a way to restore methicillin's killing power. Following on from work done in the 1990s, his team found that certain compounds containing the amino acid glycine greatly increased 20 different MRSA strains' susceptibility to methicillin. The dose needed to kill them dropped from 256 milligrams per litre to just 4 mg/l.

The problem was that the concentrations of these glycine compounds had to be very high. "You cannot drown yourself in glycine to treat infection," points out Brigitte Berger-Bachi at the University of Zurich, Switzerland. Then Levey got lucky. He learned of another glycine compound that has already been approved for human use in diagnostic tests. Lab tests show that the compound, which Levey calls BTA19976a, makes MRSA susceptible to methicillin at concentrations regarded as safe.

How it works remains mysterious, but it is thought that the glycine alters the composition of the cell wall's building blocks, preventing PBP2a reinforcing it. Pharmaceutica has now begun testing the compound in mice infected with MRSA. If it proves effective, BTA19976a could be given to patients along with methicillin to treat MRSA infections, reducing the need for other antibiotics such as vancomycin. Other teams are taking similar approaches, such as trying to design new antibiotics that block the PBP2a enzyme.

But the long-term strategy should be to prevent MRSA infections, points out Dan Jernigan of the US Centers for Disease Control. "No matter what we do, bacteria will find a way around it. But there are some things that always work. Resistant bacteria are not resistant to hand washing."