Real-Time Monitoring of Bacteria Clearance From Blood in a Murine Model

Abstract

Bloodstream infections, especially those that are antibiotic resistant, pose a significant challenge to health care leading to increased hospitalization time and patient mortality. There are different facets to this problem that make these diseases difficult to treat, such as the difficulty to detect bacteria in the blood and the poorly understood mechanism of bacterial invasion into and out of the circulatory system. However, little progress has been made in developing techniques to study bacteria dynamics in the bloodstream. Here, we present a new approach using an in vivo flow cytometry platform for real-time, noninvasive, label-free, and quantitative monitoring of the lifespan of green fluorescent protein-expressing Staphylococcus aureus and Pseudomonas aeruginosa in a murine model. We report a relatively fast average rate of clearance for S. aureus (k = 0.37 ± 0.09 min−1, half-life ~1.9 min) and a slower rate for P. aeruginosa (k = 0.07 ± 0.02 min−1, half-life ~9.6 min). We also observed what appears to be two stages of clearance for S. aureus, while P. aeruginosa appeared only to have a single stage of clearance. Our results demonstrate that an advanced research tool can be used for studying the dynamics of bacteria cells directly in the bloodstream, providing insight into the progression of infectious diseases in circulation. © 2019 International Society for Advancement of Cytometry.