Quantifying host-microbe interactions with bacterial lineage tracing

Using genomic barcodes to trace bacterial lineages within a host reveals previously unobservable dynamics of infection, including the impact of infection bottlenecks, routes of bacterial dissemination, and patterns of within-host evolution. Barcoding introduces trackable diversity to otherwise isogenic bacterial populations. Comparing the barcodes within an inoculum to those within the host quantifies the “founding population,” which reveals the magnitude of population collapse caused by host bottlenecks. Furthermore, comparisons of the founders between tissues can reveal the patterns of pathogen dissemination. On longer timescales, the emergence of dominant barcoded lineages can also be used to detect within-host evolution. Collectively, barcoding studies quantify the hidden parameters that underlie bacterial colonization and create a quantitative framework for modeling and preventing infectious disease.