Crack in Bacteria’s Armour Leads to Effectual Antibiotics Against 'super Bugs'

by VR Sreeraman on  September 7, 2007 at 8:29 PM Drug News   - G J E 4
Crack in Bacteria’s Armour Leads to Effectual Antibiotics Against 'super Bugs'
Researchers in Biomedical technology at Boston University's College of Engineering say that they have moved close to what may be called a break through in developing effective drugs that would combat super bugs that are resistant to common antibiotics.

At present, three classes of bactericidal antibiotics are used to deal with different bacterial functions—such as inhibiting DNA replication, blocking protein-building, or halting construction of cell walls.

A study from the laboratory of Professor James Collins suggests that the three antibiotics are more alike than ever realized, and that the commonalities may be the bugs' downfall.

Professor Collins and his colleagues discovered a common process that was triggered by all three types of antibiotics.

"There's an underlying pathway beyond the drug interacting with the target, and the endpoint of this pathway is excessive free radical production," said graduate student and lead author Michael Kohanski.

He said that free radicals, such as hydroxyl or superoxide radicals, are molecules that carry an unpaired electron like a weapon.

"They'll damage DNA, proteins, lipids in the membrane, pretty much anything. They're equal opportunity damagers," he said.

The researchers say that though this hidden pathway and resultant free radical overload appeared to help current antibiotics do their job, it was not always enough to kill all bacteria by itself. They believe that by amplifying this effect or by weakening cell's genetic defence against it, the emergence of antibiotic-resistant bacteria could be limited.

"Importantly, we showed that if you can inhibit or block the bacterial defense mechanisms to hydroxyl radical damage, you can potentiate or enhance the lethality of bactericidal antibiotics. This highlights the value of taking a network biology approach to antibiotics and provides a framework for creating new classes of drugs," said Collins.

"What we think is happening is the cell is getting a signal that says, 'There's something wrong with our energy production system and we need to make more energy.' But, there's really nothing wrong. The cell becomes confused, turns on too many processes at once and it's overwhelmed," said Kohanski.

During the research, the researchers used DNA microarray studies to see if all three classes of bactericidal antibiotics triggered this process, and found an increased gene activity along the intracellular assembly lines that made energy for the bacterial cell. They began to deduce the details of the new pathway.

Cells produce free superoxide radicals naturally in oxygen-rich environments. When they unnecessarily ramp up energy production to a frantic pace, such as when triggered by antibiotics, more radicals get churned out than the cell's safety measures can mop up.

The superoxide radicals then pull iron from other components of the cell, and this iron rapidly stimulates production of toxic levels of hydroxyl radicals.

"It's really amazing that despite the diversity of targets, you have everything funnelling into this common pathway, where there's a global meltdown occurring. There's almost no way for the cell to recover from this. It shows you how potent these molecules are to damaging and killing the cell," said Dwyer.

The findings, published in the journal Cell, may revitalize development of antibiotic drugs sidelined because of narrow differences between therapeutic and toxic doses, the researchers believe. They say that such drugs may re-enter the pipeline, if this free-radical producing pathway is exploited to lower the therapeutic dose, making formerly dangerous drugs safer.

Source: ANI

Post your Comments

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
User Avatar
* Your comment can be maximum of 2500 characters
Notify me when reply is posted I agree to the terms and conditions

You May Also Like

View All