drug resistant bacteria
Medical Research

Fighting The "Nightmare Bacteria"

New research could help experts fight the so-called “nightmare bacteria” as well as other superbugs.

Scientists from the University of Michigan Medical School say they have discovered more about the risk we face from one of our most dangerous microscopic foes, Klebsiella pneumoniae. They made the discovery in mice with pneumonia. K. pneumoniae has already figured out how to overcome our best defenses – including, in some cases, all our most powerful antibiotics.

It’s the third-most-common cause of infections that arise in hospitalized patients, and causes pneumonia, urinary tract infections, wound infections and bloodstream infections. In its most drug-resistant form, it’s considered one of the carbapenem resistant Enterobacteriaceae, or CRE – so called “nightmare bacteria”.

The new findings could aid the search for drugs to fight it, and other “superbugs”.

In a new paper in the journal mBio, the team led by Michael Bachman, M.D., Ph.D. report what happens after the bacteria send out tiny iron-scavenging molecules.

Called siderophores, those molecules have long been thought of as a way for bacteria to gather the body’s iron – a precious element needed to grow and reproduce – by attaching to it and stealing it from us.

Siderophores from K. pneumoniae are hundreds of times more powerful at grabbing iron than the proteins that our own bodies produce. What’s more, the bacteria produce a kind of siderophore that defense systems can’t neutralize.

But Bachman and his colleagues show that bacterial siderophores do much more than just grab iron. Their experiments show that K. pneumoniae actually use the molecules to help them invade the rest of the body beyond their initial point of entry, and to bring on inflammation caused by our own immune system.

“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,” says Bachman, an assistant professor of pathology at U-M. “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.”

That mechanism, a protein called Hif-1alpha, normally helps our bodies respond to low oxygen or low iron. But when K. pneumoniae siderophores activate it, it worsens the infection. Exactly how is still a mystery.

Bachman sees the effects of K. pneumoniae on patients in his work as a clinical microbiologist at the U-M Health System, where he’s associate director of clinical microbiology. That motivates him to study it in the lab, though he notes that it’s too early to say exactly how the discovery could be used to help patients.