'Weaponized' bacteria could hold key to abolishing antibiotic-resistant superbugs

New research shows that drug-resistant bacteria can become weaponized supersoldiers—but in doing so, lose their resistance to antibiotics.


(Edmonton) Multi-drug resistant bacteria, or “superbugs,” infect millions of people worldwide each year, straining health-care systems and resulting in tens of thousands of deaths annually. Worse, infections are increasingly being caused by pan-drug resistant bacteria, which are completely resistant to all clinically relevant antibiotics.

To date, little progress has been made toward developing new antibiotics to fight these infections, leaving us headed toward what the World Health Organization has called a “post-antibiotic era.” But researchers in the University of Alberta may now be one step closer to finding a solution to this deadly problem.

“There is a clear need to investigate other avenues to help prevent or slow the increase of antibiotic resistant infections,” says Mario Feldman, professor in the U of A's Department of Biological Sciences. In search of such avenues, Feldman and his team studied the strain of Acinetobacter baumannii responsible for a fatal 2012 outbreak in an Edmonton hospital.

In the past, A. baumannii infections have been relatively easy to treat because they were sensitive to most antibiotics. But in the past few decades, some strains have been rapidly acquiring drug resistance. And although A. baumannii has grown to become a major problem in hospitals around the world, scientists still know relatively little about the biology of this bacterium, making it even more difficult to design alternative therapeutics to treat infections.

Microscopic mercenaries

“While most people are familiar with the reality that bacteria can be fatal to people, a lesser-known fact about bacteria is that they can also kill each other,” explains Feldman. Some A. baumannii cells do this by activating a weapon called the type VI secretion system (T6SS), which enables them to inject lethal toxic proteins into other nearby bacteria, killing them.

However, this ability to kill competing bacteria comes at a cost—the “armed” bacteria lose their resistance to antibiotics once they have activated their T6SS weaponry, making them once again vulnerable to drugs. The precise reasons the bacteria do this are unknown—but learning how to harness the T6SS weapon could have huge implications in the way drug-resistant bacterial infections are treated.

“Our data suggests that you can’t have an active T6SS and be multi-drug resistant at the same time, so we are trying to determine the interplay between the two processes, especially during infection,” notes Brent Weber, PhD student at the U of A and lead author on the study.

An army of bacteria supersoldiers

Hypothetically, it could be possible to engineer an army of “good” bacteria equipped with T6SS and send them to war against dangerous bacteria like A. baumannii—similar to what happens naturally with bacteria in the human gut. In another scenario, it could be possible to target the drug-resistant A. baumannii strains to force them to activate their T6SS weaponry, which would then cause them to lose antibiotic resistance and theoretically make the infection treatable.

“I think the more likely scenario would be identifying the different ‘bullets’ of the T6SS weapon—the toxic proteins that the T6SS physically injects into other bacteria to kill them—and using these as the basis for new antibiotics,” suggests Weber. “Essentially, bacteria with a T6SS are injecting antibacterial proteins into their competitors, but require this complicated weaponry to accomplish this. If we can take the biological system out of the equation, we could use a purified version of these proteins as antibiotics.”

With a deeper understanding of what triggers and controls the transformation of the bacteria into soldiers, scientists can now start thinking about ways to develop a new class of antimicrobials that, instead of killing the bacteria, make them susceptible to the antibiotics we already know.

The findings were published in the journal Proceedings of the National Academy of Sciences.