Using ultrasound to localise engineered bacteria in a host organism

Using ultrasound to localise engineered bacteria in a host organism

January 4th, 2018

Bacetria can also be healthy for us

Our microbiome has many proven roles in mammalian – therefore human – health and disease, for example in immunity and central nervous system disorders.

Modern genetic engineering has allowed the design of microbial therapeutics and diagnostics as reported for the detection of cancer in urine, the treatment of colitis in the mouse, the use of synthetic microbes as drug delivery systems, the synchronisation of bacterial lysis cycles for in vivo delivery, or the long-term use of engineered bacteria in the mammalian gut as live diagnostics of inflammation.

Location, location, location

For all bacteria in our microbiome – whether natural or engineered – to fulfil their role in health or disease, they must be at the right location in the organism.

In the case of microbial therapy, it becomes crucial to verify the location of the introduced engineered bacteria in the treated host. The problem has so far been the limitations and invasiveness of existing imaging methods, primarily based on optical reporters. These methods can have limited deep tissue penetration and can require radioactive tracers.

No light, just gas

Today, a team of researchers from the California Institute of Technology report a new method based on acoustic reporters.

It uses genetic constructs that allow the engineered bacteria to be visualised in vivo using ultrasound. Ultrasound is a widely available inexpensive technology that allows deep tissue penetration with high spatial resolution.

These constructs code for the production of gas vesicles within the engineered bacteria. This type of vesicles are naturally expressed in water-dwelling photosynthetic organisms which use these structures to regulate a force called buoyancy (this is not a typo). In simple terms, the gas vesicles are used by these organisms to control their “sinking/floating” in their liquid environment.

It is sensitive too

This new ultrasound detection of the gas vesicles within engineered bacteria has allowed the non-invasive imaging of Escherichia coli and Salmonella typhimurium at volumetric densities below 0.01% with a resolution of less than 100 μm. In short, the technique is highly sensitive and offers a much needed solution to the monitoring of engineered bacteria in an era of tremendous genetic engineering power and increasing understanding of the role of microbiota and their therapeutic potential.

By Sarra Achouri

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