Antivirulents new hope in bacteria fight
Reported February 15, 2010
With their ability to transform sometimes-deadly infections into routine, virtually harmless illness, antibiotics still rank among history’s greatest medical discoveries.
But as many bacteria become resistant to the effects of the original miracle drug — leading to thousands of deaths a year in Canada — scientists here and elsewhere have quietly begun developing a whole new way to combat the infectious threat.
Called antivirulents, or virulence blockers, the new drugs would not actually kill bacteria, but sap their ability to harm the person they infected. With the bugs rendered innocuous, the body’s immune system could then naturally eliminate them, says a University of Montreal microbiologist in a just-published review of the cutting-edge research.
“Your immune system is your defence line. You are attacked by a soldier, by an army that has weapons and it can overcome your immune system, your defence,” Christian Baron said in an interview. “If you deprive the army of its weapons, it cannot do much.”
The medicines’ novel qualities would make it harder for bacteria to become resistant to them, a crucial attribute in light of health care’s growing resistance “crisis,” Prof. Baron says in the journal Current Opinion in Microbiology.
His own lab has already developed compounds that can neutralize the toxicity of bacteria in a test tube, yet leave the microbes alive. Others have done the same, and a small Swedish company is about to start animal studies. If trials are successful, a drug could be on the market to treat humans in as little as five years, Dr. Baron said.
Bringing a new anti-bacterial arsenal to fruition appears all but essential, experts say. So-called “superbugs” — such as methicillin-resistant staphylococcus A (MSRA) — that are impervious to a host of different medications are spreading quickly in Canada, while numerous other common bacteria, from tuberculosis to E. coli, are also developing resistance to some drugs.
An estimated 8,000 Canadians die from drug-resistant bacteria every year, said Dr. Baron, including the many cystic fibrosis patients who succumb to Pseudomonas aeruginosa, a bacteria now invulnerable to multiple antibiotics.
At the same time, drug companies see little profit potential in the market and have few new antibiotics in the pipeline.
If the problem is not fixed soon, it could become all but impossible within 10 years for people to undergo many operations, since surgical incisions open the door to infection, said Ulf Boberg, chief executive of Creative Antibiotics, the Sweden-based leader in developing antivirulents.
“Microbials will be so resistant that no one will go into surgery,” he said.
One version of the new concept being developed by his company and others disables the bacteria’s “secretion system” — a syringe-like extension of the microbe that squirts toxins into cells of its host body. Mr. Boberg calls it “the Kalashnikov of the bacteria.”
By studying the molecular structure of the secretion system, researchers are inventing compounds to neutralize it, Prof. Baron said.
The antivirulent idea is intriguing and seems to hold real promise, so long as the drugs do not prove toxic to people, said one specialist in infectious diseases.
“It’s kind of outside the box, because it’s looking at what causes the harm, and often that’s not the presence of the bacteria, it’s what the bacteria is doing,” said Edmonton’s Dr. Lynora Saxinger.
“We’ve been predicting the resistance crisis for a long time, but now it’s actually happening. It’s just happening slowly, like a slow train wreck.”
The antivirulence drugs being tested by Creative Antibiotics include one to treat salmonella and other diarrhea-causing bugs, one for sexually transmitted infections such as chlamydia, and another to target a bacteria that typically infects burn patients.
Source : www.nationalpost.com