The mammalian microbiome has many important roles in health and disease, and 
genetic engineering is enabling the development of microbial therapeutics and 
diagnostics. A key determinant of the activity of both natural and engineered 
microorganisms in vivo is their location within the host organism. However, 
existing methods for imaging cellular location and function, primarily based on 
optical reporter genes, have limited deep tissue performance owing to light 
scattering or require radioactive tracers. Here we introduce acoustic reporter 
genes, which are genetic constructs that allow bacterial gene expression to be 
visualized in vivo using ultrasound, a widely available inexpensive technique 
with deep tissue penetration and high spatial resolution. These constructs are 
based on gas vesicles, a unique class of gas-filled protein nanostructures that 
are expressed primarily in water-dwelling photosynthetic organisms as a means to 
regulate buoyancy. Heterologous expression of engineered gene clusters encoding 
gas vesicles allows Escherichia coli and Salmonella typhimurium to be imaged 
noninvasively at volumetric densities below 0.01% with a resolution of less than 
100 μm. We demonstrate the imaging of engineered cells in vivo in 
proof-of-concept models of gastrointestinal and tumour localization, and develop 
acoustically distinct reporters that enable multiplexed imaging of cellular 
populations. This technology equips microbial cells with a means to be 
visualized deep inside mammalian hosts, facilitating the study of the mammalian 
microbiome and the development of diagnostic and therapeutic cellular agents.