PBD Biotech has developed an exciting and potentially disruptive technology that uses bacteriophage to improve the molecular diagnosis of tuberculosis – I’m not aware of any comparable approaches that are commercially available at the moment,” says Dr Tomas Richardson, a specialist in DNA replication and molecular diagnostics, who is joining the company to set up a dedicated R&D laboratory and head up the research team.
Bacteriophages – literally bacteria eaters – are viruses that are specific to a particular bacterium. The phage destroys the host cell, releasing its DNA, which can then be used as a target for detection and identification.
Tomas continues: “I think phage and virus-mediated technologies are having a bit of a ‘moment’ right now as biologists start to realise their potential. Increasingly, they’re being used in a variety of different technologies. “
“We have seen their application in COVID-19 vaccine development, as viral vectors. They’re a rich source of components in the field of synthetic biology where they can be used to engineer orthologous circuits and systems in living cells. Another potential use of phages is as antimicrobials for use against antibiotic resistant bacteria, or even in the tailored engineering of the gut microbiome.“
“Phages can only infect and destroy living bacteria. What PBD Biotech has done with their Actiphage assay is combine phage technology (to detect only living bacteria) with traditional qPCR (which is extremely sensitive and specific for target DNA sequences) to create a new, highly sensitive and specific diagnostic assay that detects only live, disease-causing bacteria.”
“This is important as infectious human and bovine TB are caused only by live bacteria, so it’s extremely useful to be able to identify these targets and determine when a human or animal is likely to become infectious or develop symptoms.”
Tomas’ PhD focused on characterizing DNA polymerases in order to develop more effective enzymes for use in PCR reactions and he has first author papers in Nature and EMBO. He helped manage a large team of researchers at Newcastle University Medical School before joining BioChek (UK) Ltd where he led the design, development, and validation of multiplex qPCR and RT-qPCR kits for sale into the veterinary diagnostics market.
“In my previous role, as principal R&D scientist, I set up a qPCR facility from scratch. The company had historically focussed mainly on serological (ELISA) testing for diagnosing a wide range of diseases, but are now moving more into molecular diagnostics, using qPCR-based methods.”
“ELISA is an immunological assay, which can be used to detect the presence of host antibodies against a pathogen, whilst PCR-based methods detect genetic material from the pathogen itself. There are pros and cons with both methods and each may be more or less appropriate, depending on the intended application.”
The current skin test for bovine tuberculosis is an immunological test that assesses the immune response to TB antigens injected into the skin and is known to miss up to 25% of carriers of the disease in the herd. Use of Actiphage would provide a simple yes/no answer to the presence of the mycobacteria that cause the disease, providing early detection of the disease before the animals become infective.
Tomas continues: “Actiphage could be developed into a ‘multiplex’ assay that can diagnose multiple diseases simultaneously – that’s something I’m looking forward to helping with, having developed similar assays in my previous role. By developing and optimising the qPCR part of the assay, focusing on slight genetic differences, Actiphage could also potentially be employed as a DIVA assay, to ‘Distinguish Infected from Vaccinated Animals’.”
“But the first step is to achieve World Organisation for Animal Health (OIE) validation so that’s the priority at the moment.”
PBD Biotech CEO Jane Theaker said: “There is a huge global unmet need for a tuberculosis diagnostic - 1.5 million people died worldwide from TB in 2020 - with an effective diagnostic many of these deaths can be prevented and we are delighted to have Tomas, with his depth of relevant knowledge and experience, onboard to drive forward development of Actiphage. There is no time to waste.”