Bacteria Probe

The Problem

Currently, clinicians rely on x-rays, airway samples and blood tests for the diagnosis of bacterial infections deep in the lung, but these can be slow, prone to contamination and therefore imprecise. Patients are often treated with many different antibiotics as a precaution, which exposes them to potential side effects and contributes to the emergence of antimicrobial resistance (AMR) in bacteria.

Since different antibiotics interact in different ways depending on what type of bacteria they are attacking, it is vital that clinicians are able to tell exactly which cells are causing the infection in order to be able to treat it correctly and efficiently.

The Solution

Tiny amounts of chemical SmartProbeswill be sprayed into the deepest parts of the human lung, emitting light when they attach to specific types of bacteria in a physical process known as ‘fluorescence’. The fluorescence is detected using tiny fibre optic tubes that are inserted deep into the patient’s lung through a bronchoscope. The glowing bacteria are then shown on a screen at the patient’s bedside, thus allowing clinicians to see what is causing the infection within just 60 seconds.

This will potentially revolutionise how lung infections are assessed and treated. Most importantly, this technology will allow clinicians to decide which antibiotics should be continued and which can be safely stopped.

A cut-away diagram of a bacterium, showing where the capsule, cell wall and membrane are located.

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The Method

All bacteria can be categorised as one of two types, depending on their structure: ‘Gram-positive’, or ‘Gram-negative’.

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Traditionally, clinicians must take a sample from the patient to a laboratory in order to carry out tests and determine what the bacterial infection is.

In the lab, a water-soluble dye called crystal violet is used to distinguish between Gram-positive and Gram-negative bacteria.  During the process, called ‘Gram staining’, Gram-positive bacteria turn violet due to their thick cell wall which retains the crystal violet. Gram-negative bacteria turn red due to it having a thinner cell wall, which does not retain the crystal violet.
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    Gram-negative bacteria                                               Gram-positive bacteria

Proteus has developed two bacterial SmartProbes which couldremove the need to take a sample to a lab in order to determine whether it is Gram-positive or Gram-negative bacteria causing the infection.

The BAC ONE SmartProbe is used first, as it can identify allof the bacteria present in the patient. The SmartProbe inserts itself into the bacteria membranes, binds to them, and fluoresces. This fluorescence is then viewed on a screen at the bedside.

The BAC TWO Smartprobe is used next to distinguish between Gram-positive and Gram-negative bacteria. BAC TWO inserts itself into the membrane of Gram-negative bacteria and fluoresces, making it detectable.

By using the two SmartProbes in conjunction with each other, the clinician is able to tell whether both Gram-positive and Gram-negative bacteria are present, or just Gram-negative. The appropriate antibiotics can then be administered by the patient’s doctor.

Both bacterial probes have been extensively tested in the Proteus labs, and are now in the process of being tested in humans for the first time as part of on-going clinical trials. This is the first time that SmartProbes like these have been used in the clinic for bacterial detection.

This video was created by Ellie Cawthera, with contributions from Hannah Stewart and Caroline Lyth
(MSc Science Communication and Public Engagement at the University of Edinburgh)
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