The smaller they are the harder they fall

In the trenches with the bacteria beaters. There is something that does not love a wall

By Amanda Alvarez

The idea that bacteria have been winning the war against antimicrobials is firmly fixed in the public's mind. Hospitals are, with some justification -- and much media hype -- often seen as dangerous breeding grounds of infection to be avoided at all costs, especially if you're sick. Our last issue (NRM, Vol 1, No 5, March 15, 2004) contained two articles on the subject, The gate-crasher from hell and Finally some good news about Streptococcus pneumoniae. The latter highlighted the success Canada has had in reducing the rate of infection in the last couple of years; the former detailed the progress researchers have made in investigating bacteria, immunity to antibiotics. It's exciting work and can yield astonishing insights into just how clever these little bugs are. It can also point the way to unexpected victories by those in the white coats.

A case in point occurred not long ago in Dr Alexander Tomasz's lab at Rockefeller University in New York. It all started back in June 2002 when a 40-year-old Michigan man with diabetes, heart disease and kidney failure developed gangrene and had a toe amputated. He was being treated with a whole slew of antibiotics, including methicillin and vancomycin. Hospital staff were then alarmed when the man developed a second infection at the site of the catheter used for dialysis. It turned out to be the deadly microbe Staphylococcus aureus, and this marked the first time it had ever managed to beat vancomycin. Four months later a similar case surfaced in a Pennsylvania hospital.

A research team headed by Dr Tomasz has now determined how the bacteria foiled both of its attackers. Their findings were announced in the February 27 Rockefeller University Scientist.

In the case of methicillin, the drug works by inactivating four penicillin-binding proteins that the bacterium needs to construct its cell wall. The wily staph managed to acquire a gene called mecA, which produced a new protein to take over cell-wall construction. Vancomycin works by physically trapping the same proteins to prevent cell-wall building. To outwit this attack, the staph acquired another gene, this one called vanA, which produces an abnormal cell wall precursor that the antibiotic doesn't recognize. Score two for the staph.

Working with both vancomycin and methicillin, Dr Tomasz and his coresearcher, Dr Anatoly Severin, discovered that the new methicillin-resistant protein produced by the staph couldn't use the abnormal cell-wall precursor to resist vancomycin. Not only that, the drug combination turned out to be effective even at low doses. And there was more. The doctors also showed that the cell wall built using the abnormal precursor has several weaknesses that make it less likely to spread in those with healthy immune systems.