In a groundbreaking study, scientists at U-M Medical School have identified two distinct ways pneumonia-causing bacteria invade the bloodstream. This discovery could pave the way for innovative treatments for life-threatening blood infections.
Researchers led by the University of Michigan Medical School have made a significant breakthrough in understanding how bacteria responsible for pneumonia spread into the bloodstream. This discovery could have profound implications for treating bacteremia, a severe and often fatal condition.
Bacteremia, often referred to as blood poisoning, occurs when bacteria overpower the body’s immune defenses. If unchecked, this can escalate into sepsis, a severe condition responsible for more than one-third of hospital deaths annually in the United States.
Scientists have long sought to understand the exact mechanisms behind these bacteria’s ability to infiltrate the bloodstream and cause systemic infection.
The research team, led by Michael Bachman, a clinical associate professor of pathology and microbiology and immunology, and former postdoc Caitlyn Holmes, focused on Klebsiella pneumoniae, a gram-negative bacterium commonly associated with pneumonia-initiated bacteremia.
Their study, published in Nature Communications, sheds light on how these bacteria transition from lung infections to bloodstream invaders.
“Experimentally, we can measure the first phase pretty easily in terms of how the bacteria infect the lungs and we can measure the third phase pretty easily in terms of how the bacteria survive in these blood-filtering organs and whether they replicate or not. But that transition out of the lungs and into the bloodstream has traditionally been difficult to measure,” Bachman said in a news release.
Using an innovative barcoding-style system developed with Harvard University colleagues, the team labeled bacteria with short DNA snippets in mouse models, allowing them to track the movement of K. pneumoniae throughout the body. Their findings revealed two distinct dissemination patterns: metastatic dissemination and direct dissemination.
Metastatic dissemination was expected; bacteria replicate in the lungs until they breach the lung defenses and spill into the bloodstream. Surprisingly, the researchers discovered that direct dissemination occurs when bacteria escape into the bloodstream without significant replication in the lungs first.
“[A]bout half of the mice had the metastatic pattern, and the other half contained bacteria that escaped on their own into the bloodstream without the need to replicate to large numbers first,” added Bachman.
This unexpected finding of direct dissemination has profound implications on understanding and treating bacterial infections.
Moreover, the study noted that infections tend to evolve towards a metastatic pattern over time, correlating with stronger infections. Understanding both dissemination routes could lead to new, more effective treatments by targeting specific bacterial behaviors and interactions with the immune system.
“We need to understand the biology of each of these routes in order to figure out the best treatments,” Bachman added. “There’s a mantra in infectious disease that is to find and treat the source to stop the bacteremia.”
Furthermore, Holmes delved deeper by creating bacterial and mouse mutations to observe their effects on dissemination, hinting that these interactions might determine infection outcomes.
“The project began with a very basic question — how does bacteria leave the lungs — that we have now provided some insight into, closing a significant gap in our knowledge,” Holmes said in the news release.
The study not only advances our understanding of bacterial infections but also opens avenues for developing targeted therapies to combat life-threatening bloodstream infections.