Cocktail of viruses holds promise as an alternative treatment for Klebsiella pneumoniae infections
Researchers have concocted a cocktail of bacteria-fighting viruses with the potential to successfully treat antibiotic-resistant Klebsiella pneumoniae infections.
In a recent study, researchers led by Mark Mimee at the University of Chicago Pritzker School of Molecular Engineering (IL, USA) created a mixture of bacteria-attacking viruses, known as bacteriophages, that holds promise as an alternative to treating antibiotic-resistant Klebsiella pneumoniae.
K. pneumoniae are normally harmless bacteria found in the gut; however, they can cause serious illness if they infect other parts of the body, such as the bloodstream or the urinary tract. In the hospital environment, these bacteria can spread quickly and are becoming increasingly resistant to common antibiotics. Now, researchers are looking for alternative ways to treat antibiotic-resistant K. pneumoniae infections.
Bacteriophages are one such alternative, with potential to make antibiotic-resistant bacteria more susceptible to the immune system or antibiotics. However, these viruses, known as phages, come with their own set of limitations: they are usually specific to one type of bacteria, and bacteria can become resistant to phage infection. Using a mixture of phages, or a ‘phage cocktail’, is more effective against multiple types of bacteria and reduces the risk of phage resistance.
Coming of phage: treating antibiotic-resistant infections with bacteriophages
In this interview, Martha Clokie talks about phages’ diverse structure and function, the roles that both natural and engineered phages could play in overcoming the growing issue of antibiotic-resistant bacterial infections and what happens if bacteria become phage-resistant.
In the study, research specialist Ella Rotman and colleagues screened a library of phages isolated from wastewater against a selection of antibiotic-resistant Klebsiella strains to identify bacterial genes associated with good susceptibility to phage infection. Using this information, they then developed a combination of five phages designed to target K. pneumoniae. This cocktail was tested both in culture and a mice model.
While the phage cocktail made some isolates more susceptible to immune attacks and treatment with antibiotics, in other cases the bacteria became more resistant to antibiotics or phage infection after treatment.
“It’s one of those things where biology often doesn’t work the way you want it to,” commented Mimee. “But it allows us an opportunity to study the detailed dynamics between the phages and the bacteria.”
The team went on to find that, with further exposure to isolates, phages countered the evolution of Klebsiella by evolving to more effectively infect the bacteria. This co-evolution of phages and Klebsiella was also observed in mice.
The Mimee lab plans to continue its investigation of the interactions between phage–bacteria pairs, as well as how they’re influenced by other phages and bacteria in the body. “We still think phages are an incredibly promising approach to treating drug-resistant bacteria such as Klebsiella,” said Mimee. “But phages are like a living, constantly changing antibiotic which gives them a lot of complexity.”
“This research is a positive step forward in trying to sort out the complexities of phages and move them closer to the clinic.” The team is currently seeking approval from the Food and Drug Administration for a small clinical trial of the phage cocktail in patients with urinary tract infections.
