A team of scientists from India, Sweden and Japan has developed a new diagnostic tool capable of keeping pace with rapidly mutating bacteria and viruses.
At a time when the world has seen first-hand how novel germs – like SARS-CoV-2 and its variants – can disrupt life on a large scale, researchers say their new tool could speed up the discovery of new viral and bacterial variants, helping combat them quickly and effectively.
"Emergence of novel zoonotic infections among the human population has increased the burden on global health-care systems to curb their spread," the authors published in the peer-reviewed scientific journal ACS Infectious Diseases on Wednesday.
"To meet the evolutionary agility of pathogens, it is essential to revamp the existing diagnostic methods for early detection and characterization of the pathogens at the molecular level."
The tool, a computer program called AutoPLP, builds on the technology polymerase chain reaction (PCR) tests use to detect viruses and bacteria based on their genetic material. PCR tests use – short, single-stranded sequences of DNA or RNA coded to match a specific pathogen – to diagnose infections by searching for the matching DNA or RNA associated with the pathogen they're testing for.
Rolling circle amplification (RCA) tests work similarly to PCR tests, but are known for being more sensitive than PCR tests because they use a special, more precise type of nucleic acid probe called a padlock probe (PLP). This makes them useful for detecting mutated genetic sequences, like those in novel viruses and viral variants.
The caveat is, because padlock probes are so precise, it takes more work to pinpoint specific genetic sequences for them to target. On top of that, as a pathogen mutates, its genetic sequence changes as well, forcing scientists to redesign their probes each time.
So researchers Sowmya Ramaswamy Krishnan, Ruben R. G. Soares, Narayanan Madaboosi, and M. Michael Gromiha set out to develop a software program that could keep up with viral and bacterial mutations better than human scientists can.
AutoPLP designs PLPs automatically to match genetically mutating bacteria and viruses, while systematically considering "all the necessary technical parameters at once to make the entire process easier and more robust."
The program can take the genome sequences of similar pathogens as input and run a series of analyses and database searches, producing a set of customized PLP sequences.
The authors tested the tool by having it design probes to detect the rabies virus and drug-resistant strains of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. The probes designed by AutoPLP worked more quickly, accurately and easily than previous probes developed to detect these pathogens.
The authors hope the tool will hasten the discovery of new viral and bacterial variants and help "combat them rapidly and effectively via precise molecular diagnostics," according to a issued on Wednesday.
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