Bacterial barcoding reveals two patterns of lung dissemination throughout early Okay. pneumoniae bacteremia. Credit score: Nature Communications (2025). DOI: 10.1038/s41467-025-56095-3
Bacteremia, or blood poisoning, happens when micro organism overcome the physique’s immune defenses. Bacteremia can worsen into sepsis, a situation that accounts for greater than 1 in 3 hospital deaths per 12 months. But individuals are routinely uncovered to and struggle off micro organism from the atmosphere with out this lethal collection of occasions occurring.
Scientists try to determine precisely how micro organism unfold all through the physique to trigger systemic an infection within the hopes of ultimately stopping this course of in its tracks.
Michael Bachman, M.D., Ph.D., scientific affiliate professor of pathology and microbiology and immunology at U-M Medical Faculty and former postdoc Caitlyn Holmes, Ph.D., have tried to unravel this thriller, specializing in gram unfavourable micro organism like Klebsiella pneumoniae, a standard supply of pneumonia-initiated bacteremia.
In earlier work, they decided that micro organism unfold in three phases: an infection of an preliminary website, such because the lungs; entrance into the bloodstream; and eventually, replication and avoidance of filtration by the liver and spleen.
Historically, analyzing a bacterial an infection is completed by culturing tissue and counting the variety of ensuing micro organism.
“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,” mentioned Bachman.
Utilizing an revolutionary barcoding-style system developed with colleagues at Harvard College, Bachman, Holmes and their workforce have been in a position to label micro organism with brief snippets of DNA in mouse fashions and use pc evaluation to trace the motion of Okay. pneumoniae all through the physique. The findings are printed within the journal Nature Communications.
They anticipated that the micro organism would replicate within the lungs till such some extent that their clones overwhelmed the lung’s defenses, spilling out into the blood stream, says Bachman.
And whereas they did see such a unfold—which they referred to as metastatic dissemination—there was proof of one other kind as nicely.
Unexpectedly, “about 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,” Bachman defined about this second mode, which they referred to as direct dissemination.
Total, the metastatic pathway correlated with a stronger an infection than the direct route.
Moreover, over time, an infection progressed to extra of the metastatic sample.
“We need to understand the biology of each of these routes in order to figure out the best treatments,” mentioned Bachman.
“There’s a mantra in infectious disease that is to find and treat the source to stop the bacteremia.”
Uncovering the existence of the direct route might imply that micro organism are establishing low-level reservoirs in different components of the physique that may very well be higher focused to deal with blood infections.
Moreover, Holmes created mutations in each the Okay. pneumoniae and mice that affected the mode of dissemination, hinting that the interplay between the micro organism and the host’s immune system might decide the result of the an infection.
“The project began with a very basic question—how do bacteria leave the lungs—that we have now provided some insight into, closing a significant gap in our knowledge,” mentioned Holmes.
Extra info:
Caitlyn L. Holmes et al, Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung, Nature Communications (2025). DOI: 10.1038/s41467-025-56095-3
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