Assessing microbiome population dynamics using wild-type isogenic standardized hybrid (WISH)-tags

Microbiomes feature recurrent compositional structures under given environmental conditions. However, these patterns may conceal diverse underlying population dynamics that require intra-strain resolution. Here, we developed a genomic tagging system, termed wild-type isogenic standardized hybrid (WISH)-tags, that can be combined with quantitative PCR and next-generation sequencing for microbial strain enumeration. We experimentally validated the performance of 62 tags and showed they can be differentiated with high precision. WISH-tags were introduced into model and non-model bacterial members of the mouse and plant microbiota. Intra-strain priority effects were tested using one species of isogenic barcoded bacteria in the murine gut and the Arabidopsis phyllosphere, both with and without microbiota context. We observed colonization resistance against late arriving strains of Salmonella typhimurium in the mouse gut, whereas the phyllosphere accommodated Sphingomonas latecomers in a proportional manner to their presence at the late inoculation timepoint. This demonstrates that WISH-tags are a resource for deciphering population dynamics underlying microbiome assembly across biological systems.