Population dynamics reveal bottlenecks during neonatal infections with non-typhoidal Salmonella

Non-typhoidal Salmonella (NTS) are a common global health concern in human and veterinary medicine. Whereas healthy adults usually suffer from self-limiting gastroenteritis, children younger than 5 years are at increased risk for systemic distribution, often leading to severe and potentially life-threatening conditions. After oral uptake, NTS secrete a variety of effector proteins encoded by Salmonella Pathogenicity Islands (SPIs) to overcome the epithelial barrier in the intestine. In previous studies, we identified SPI2 effectors as essential for epithelial evasion and subsequent systemic dissemination in the neonate host.

Our objective is to attain a deeper understanding of egress mechanisms, selection processes as well as potential bottleneck identification during NTS pathogenesis.

Wild-type isogenic tagged strains (WITS), either in a wt NTS or SPI2-deficient background, are orally applied to newborn mice in accordance with our previously established neonatal infection model. Tissue was harvested at 2 or 4 days post infection (dpi) and sequence abundance comparison of populations isolated from distinct organ compartments within the same host allow us to draw conclusions of disseminative pathways.

Intestinal inflammation imposed a bottleneck in wt-infected animals in the small intestine. A few founder bacteria reach systemic compartments after oral uptake independent of SPI2. However, wt bacteria successfully transmigrate the intestinal epithelium and disseminate to systemic sites. Consequently, bacterial loads in liver tissue of wt-infected neonates increased between 2 and 4 dpi, whereas SPI2-deficient bacterial loads remained similar. Sequencing revealed an assimilation of subpopulations at systemic sites compared to bacteria isolated from the intestine within 4 days in the wt background. In contrast, subpopulations in systemic organs and gut of the same host infected with SPI2-deficient WITS display low similarities.

Epithelial transmigration is the source of the majority of bacteria isolated from systemic site dependent on SPI2 effector proteins.