Bioluminescent Imaging Reveals Novel Patterns of Colonization and Invasion in Systemic Escherichia coli K1 Experimental Infection in the Neonatal Rat. Systemic E. coli K1 colonization and invasion

Key features of Escherichia coli K1-mediated neonatal sepsis and meningitis, such as a strong age-dependency and development along the gut-mesentery-blood-brain course of infection, can be replicated in the newborn rat. We examined temporal and spatial aspects of E. coli K1 infection following initiation of gastrointestinal colonization in two-day-old (P2) rats after oral administration of E. coli K1 strain A192PP and a bioluminescent derivative that retained the high level of virulence of the parental strain. A combination of bacterial enumeration in the major organs, 2D bioluminescence imaging and 3D diffuse light imaging tomography with integrated μCT indicated multiple sites of colonization within the alimentary canal; these included the tongue, esophagus and stomach in addition to the small intestine and colon. After invasion of the blood compartment, the bacteria entered the central nervous system, with restricted colonization of the brain, and also invaded the major organs in line with increases in the severity of symptoms of infection. Both keratinized and non-keratinized surfaces of esophagi were colonized to a considerably greater extent in susceptible P2 neonates compared to corresponding tissues from infection-resistant nine-day-old rat pups; the bacteria appeared to damage and penetrate the non-keratinized esophageal epithelium of infection-susceptible P2 animals, suggesting the esophagus may represent a portal of entry for E. coli K1 into the systemic circulation. Thus, multimodality imaging of experimental systemic infections in real time indicate complex dynamic patterns of colonization and dissemination that provide new insights into E. coli K1 infection of the neonatal rat.