“Because [Pseudomonas aeruginosa] can be totally resistant to all antibiotics that we know, it can become an incurable infection. There is a need for alternative or complementary strategies to antibiotic treatment.”
When it comes to causing an infection, bacteria that can communicate with each other are often better at it. A new study by Mikael Elias, an assistant professor in the department of Biochemistry, Molecular Biology and Biophysics, and his colleagues shows that a treatment that quashes bacterial communication could reduce infection severity and even death in rats. They recently published their findings in the journal PLoS One.
The pneumonia-causing bacterium Pseudomonas aeruginosa communicates via a system known as quorum sensing, with the cells each secreting a small amount of a signal, called a lactone. When lactone concentration is high enough, it tells the bacteria that there are enough of them around – a quorum – to increase their chances of beating the host’s immune system. The bacteria then produce virulence factors that allow them to invade nearby lung cells, and they form an antibiotic- and immune system-resistant community called a biofilm.
“Pseudomonas aeruginosa is the main opportunistic pathogen in hospitals, so when you have an injury or are very weak, this is the guy that will get you,” Elias says.“Because it can be totally resistant to all antibiotics that we know, it can become an incurable infection. There is a need for alternative or complementary strategies to antibiotic treatment.”
That treatment comes in the form of an enzyme, called lactonase, that degrades the lactone signaling molecule and prevents the bacteria from talking to each other.
Elias and his colleagues first showed that the lactonase reduced the ability of the Pseudomonas to express known virulence factors and form biofilms when grown in the lab. Next, they infected rat lungs with the bacteria. Some rats were left untreated, and all of them succumbed to pneumonia. However, some of the rats inhaled the lactonase, and nearly all of them survived.
“We showed that there is a therapeutic potential,” Elias said, adding that lactonase is active against any bacterial species that communicates with lactones.
Importantly, the researchers found that the number of bacteria in the lungs did not differ between those mice that succumbed to pneumonia and those that survived, indicating a key difference between this treatment and antibiotics, which work by killing bacteria.
“You may assume that if you do not kill the bacteria, the selection pressure is much lower, so resistance to this enzyme may occur much, much more slowly,” Elias says.
Elias notes that this enzyme currently can only be used as a preventive treatment, because once the bacterial quorum has been reached, it is too late for the enzyme to be effective. Still, he envisions many uses for it, and thinks it will work well in combination with antibiotic therapies.
“For cystic fibrosis patients who are prone to Pseudomonas infections, this approach is promising. We are working towards the development of enzyme-based inhalers, that could be used once a day or a few times a week, as a preventive strategy,” Elias says. He is also investigating coating medical devices, such as catheters, with the enzyme or using it topically on band-aids or severe burn wounds.
– Sarah Perdue