Distinct Pathways for Bacterial Spread in Bloodstream Infections Revealed in New Study

Researchers from the University of Michigan Medical School have uncovered new insights into how bacteria spread throughout the body during bloodstream infections. The study, led by Michael Bachman and Caitlyn Holmes, focused on gram-negative bacteria like Klebsiella pneumoniae, a common cause of pneumonia-initiated bacteremia.

Using an innovative DNA barcoding system, the team tracked the movement of K. pneumoniae in mouse models. They discovered two distinct pathways of bacterial dissemination: metastatic dissemination, where bacteria replicate in the lungs until their numbers overwhelm lung defenses, spilling into the bloodstream; and direct dissemination, where individual bacteria escape into the bloodstream without extensive replication in the lungs.

"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," explained Dr. Bachman, senior author of the paper published in Nature Communications. The metastatic pathway was associated with stronger infections and became more prevalent over time.

This discovery challenges the traditional approach to treating bloodstream infections, which focuses on finding and treating the source. Dr. Holmes noted that the interaction between bacteria and the host's immune system may influence the dissemination mode. She created mutations in both K. pneumoniae and mice that affected the dissemination pattern, suggesting potential targets for future treatments.

This research provides crucial insights into the complex process of bacterial spread during bloodstream infections. Dr. Holmes concluded, "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."