Photonic detection of bacterial pathogens in living hosts

TLDR

Traditional ex vivo assays limit pathogen studies; in vivo analyses would enhance understanding of infectious diseases. The study develops a method to detect bacterial pathogens in living hosts and uses it to compare virulence of Salmonella typhimurium strains in mice. The method employs bioluminescent Salmonella strains marked with luciferase plasmids, detects photons transmitted through tissues to localize bacteria, and monitors antibiotic efficacy in vivo. The approach distinguishes progressive from persistent or abortive infections, suggests the caecum may be pivotal in pathogenesis, and enables real‑time non‑invasive monitoring of pathogenic events and drug efficacy.

Abstract

The study of pathogenic is often limited to ex vivo assays and cell‐culture correlates. A greater understanding of infectious diseases would be facilitated by in vivo analyses. Therefore, we have developed a method for detecting bacterial pathogens in a living host and used this method to evaluate disease processes for strains of Salmonella typhimurium that differ in their virulence for mice. Three strains of Salmonella were marked with bioluminescence through transformation with a plasmid conferring constitutive expression of bacterial luciferase. Detection of photons transmitted through tissues of animals infected with bioluminescent Salmonella allowed localization of the bacteria to specific tissues. In this manner progressive infections were distinguished from those that were persistent or abortive. We observed patterns of bio‐luminescence that suggested the caecum may play a pivotal role in Salmonella pathogenesis. In vivo efficacy of an antibiotic was monitored using this optical method. This study demonstrates that the real time non‐invasive analyses of pathogenic events and pharmacological monitoring can be performed in vivo.