Researchers found that Klebsiella pneumoniae, a bacteria species that causes severe infections such as pneumonia, works by taking advantage of the immune system to spread the infection to other parts of the body.
The study, by researchers at the University of Michigan Medical School, is titled “Klebsiella pneumoniae Siderophores Induce Inflammation, Bacterial Dissemination, and HIF-1α Stabilization during Pneumonia,” and published in the journal mBio.
K. pneumoniae is one of the most common causes of infections in hospitalized patients, ranging from pneumonia to urinary tract, wound or bloodstream infections. In its more extreme and dangerous forms, it is a so-called “nightmare bacteria” because it resists even the most powerful antibiotic treatments.
When it enters the body, these bacteria send out molecules specialized in the search for iron, an essential element for the survival of both human and bacterial cells. These molecules, called siderophores, have a great capacity to gather iron from human organs, an effect that the immune system is not able to stop.
Researchers used mice to investigate the role of siderophores in promoting K. pneumoniae infection. To do so, they created a form of the bacteria that produces siderophores no longer able to return to their original cells carrying iron, allowing the researchers to study these molecules without exacerbating the infection in the animals.
The team observed that the presence of siderophores in the lungs of the mice activated the immune system, causing both the release of immune cells to fight the infection and the onset of inflammatory mechanisms. This process also activated a protein, called Hif-1 alpha, which helps the body respond to conditions of low oxygen or low iron. The bacteria took advantage of this protein to collect even more iron, worsening the infection and spreading it elsewhere.
“This is a bacterium that has evolved new ways to get iron, and it turns out that the mechanism it uses also causes cellular stress during infections,” Michael Bachman, MD, PhD, the study’s lead, said in a news release. “That response triggers an immune response that tells our bodies to fight the infection, but it also activates a mechanism that allows bacteria to escape and travel to the rest of the body.”
However, when the Hif-1 alpha protein was eliminated from the cells lining the mice’s lungs, most of the bacteria were no able to escape from the lungs and start traveling.
Together, these results suggest that several possible therapeutic strategies against K. pneumoniae infection: blocking the production of siderophores, creating a vaccine to help the immune system recognize these molecules as invaders, or using siderophores to carry antibiotics instead of iron back to the bacteria, causing its cells to die.