Bacteria are fast evolving resistance to antibiotics, and one of the most worrying of these so-called “superbugs” is Klebsiella pneumoniae. Once largely confined to hospitals, more deadly and drug-resistant forms of the bacteria are now spreading around the world. Thankfully a new vaccine has shown promise against the bug in tests on mice.
K. pneumoniae has been a pest in hospitals for years, often infecting patients there for other reasons. It causes some types of pneumonia, as well as infections of the bloodstream and liver, and has developed resistance to many antibiotics, including those considered our last line of defense. It was only really dangerous in children, the elderly, or those with weakened immune systems – until recently.
“For a long time, Klebsiella was primarily an issue in the hospital setting, so even though drug resistance was a real problem in treating these infections, the impact on the public was limited,” says David Rosen, co-author of the new study. “But now we’re seeing Klebsiella strains that are virulent enough to cause death or severe disease in healthy people in the community. And in the past five years, the really resistant bugs and the really virulent bugs have begun to merge so we’re beginning to see drug-resistant, hypervirulent strains. And that’s very scary.”
Since drugs have a hard time killing bacteria after they take hold, it’s probably a better idea to prevent them taking hold in the first place. So the researchers from Washington University in St. Louis set out to make a vaccine against K. pneumoniae. They targeted two particular strains – known as K1 and K2 – that together make up about 70 percent of all cases.
As with any vaccine, the idea is to train the patient’s immune system to recognize the invaders and be ready to fight them off before they even arrive. To do so, the team made the vaccine out of the sugars that normally coat the bacteria. These are connected to a certain protein that make the vaccine more effective, using a bacterial enzyme as a kind of glue. To speed up the chemical synthesis process, the researchers genetically engineered a strain of E. coli that produced the proteins and sugars for them.
Then the team tested it out on mice. They gave groups of 20 animals three doses of the vaccine, two weeks apart, while another group got a placebo. Next, they introduced small amounts of either K1 or K2 bacteria.
The researchers found that of the placebo group, only 20 percent of mice infected with K1 survived, and 70 percent of those with K2. The vaccinated mice fared better though, extending survival rates to 80 percent for K1 and 100 percent for K2.
“We are very happy with how effective this vaccine was,” says Mario Feldman, first author of the study. “We’re working on scaling up production and optimizing the protocol so we can be ready to take the vaccine into clinical trials soon.”
Ideally, the team hopes to get the vaccine up and running in humans before the K. pneumoniae potentially turns into a pandemic.
The research was published in the journal PNAS.
