Project Summary
Gut bacteria associate with host tissues and alter host physiology, impacting lifespan and aging.
Some types of bacteria, such as Lactobacilli, benefit health while others degrade it. A key gap in
our knowledge is how the host constructs microenvironments that coordinate colonization by
specific bacteria. In particular, which host cells (Aim 1), genes, and molecules (Aim 2) promote
colonization by specific bacteria? As an important step forward, this proposal aims to investigate
host mechanisms of bacterial colonization in Drosophila melanogaster using recently isolated
bacterial strains of Lactobacillus plantarum and Acetobacter from a wild D. melanogaster, which
are found to colonize a tightly-defined physical space in the fly gut. L. plantarum, is a probiotic in
humans, and the fly provides unique and powerful genetic resources to study homologs of human
disease genes. This proposal harnesses several unique assays developed to identify host
mechanisms that mediate commensal strain specificity, including the host cell types, genes and
molecules that recruit and maintain commensal bacteria. The central hypothesis is that specific
cell types in the fly foregut produce a "commensal niche": a specialized chemical and physical
microenvironment that facilitates adhesion and proliferation of specific bacteria that may benefit
the host. The proposal aims to (i) use single cell RNA sequencing to identify the specific host cell
types and genes that create this specialized microenvironment. This will enable the use of
Drosophila genetics to (ii) probe the mechanisms of host tissue maintainance through cell
turnover and localized secretion of a defined extracellular matrix. As a critical test of the
hypothesis, the proposal will examine the L. plantarum population kinetics that enable its
association with the commensal niche. By studying commensal niche construction in the
Drosophila gut, this research will establish a new paradigm that enables interrogation of the
conserved molecular and cellular interactions between hosts and their commensals that influence
host health. The proposal holds translational potential for developing tools to drive these beneficial
interactions.