Novel strategies in the fight against resistant bacteria

You and your family have probably heard that for years now. All over the world we are seeing a rise of bacteria that has developed ways to resist the harm drugs should cause them. At the same time as health care officials are trying to limit the spread of resistant bacteria, researchers are looking for alternatives to antibiotics.

One of the researchers who has taken up the challenge is Ann-Beth Jonsson, professor in bacterial pathogenesis at Uppsala University in Sweden. “We might reach a situation where we cannot cure simple bacterial infections and then our own immune system has to take over, and we can see how cleverly the bacteria escape this defence. Therefore we must find new ways to attack the disease-spreading ability of the bacteria”.

She is developing a method that will prevent many types of bacteria from reaching our cells. So how would this new drug attack these bacteria? Imagine that you are in a kayak. You put your paddle onto a pier and use your muscle power, like a motor, to pull the kayak close to the pier to enter the new place. These bacteria have long hairlike structures, called pili, which are protruding from their cell surfaces. Like you use the paddle, the bacteria use their pili to adhere to the cell surface (the pier), drag themselves close with the help of motors (muscle power) and then enter the cell (the new place). By developing a drug that inhibits the motors of the pili the bacteria become paralysed and cannot enter the cell. We could therefore avoid many bacterial infections.

While Jonsson and colleagues are trying to find a substance that can stop these motors which are present in many bacteria, another research group is instead aiming to make holes in the bacteria. The leader of this group is Martin Malmsten, professor in physical chemistry at Uppsala University in Sweden. His team has antimicrobial peptides in their arsenal to render the bacteria harmless. Antimicrobial peptides are small proteins which are made when proteins break down in the body, every time a bacterial infection arises.

“This research is motivated by the increasing problems concerning resistance against traditional antibiotics. We believe that these antimicrobial peptides give rise to rather limited development of resistance in bacteria,” Malmsten said.
His team investigates how antimicrobial peptides bind to artificial cell membranes, equivalent either to the outer wall of a bacterial or human cell. To be useful, the antimicrobial peptides need to attack the bacterial cell membrane while leaving the human cell membrane intact.
They have seen that antimicrobial peptides can differ between friend and enemy, and the team is now trying to find out what makes this possible. When this problem is resolved, the challenge of delivering the peptides into the body remains.

“The intestine has an enzyme system and other processes with the purpose of breaking down proteins, for example meat or other things we eat, so the administration of antimicrobial peptides might be through the skin or mucous membranes. We are looking for different ways of enclosing the peptides in order to protect against, for example, degradation by enzymes.”

Jonsson and Malmsten still have many studies to conduct before their novel approaches for fighting bacterial infections might be available to patients.

(17 June 2010)

Annette Östrand