Engineered Bacteria Detect Mutations in Human DNA, Allowing Biosensors To Identify Tumors in the Body

With the advancement of medical technology, a lot of diseases can be detected, prevented, and cured using cells instead of pills. Synthetic biology has enabled the development of complex cellular biosensors that can detect and respond to human disease. However, they have not yet been modified to identify specific sequences and mutations in human DNA.

A New Tool Against Cancer

In a new study conducted at the University of California San Diego, a group of scientists used synthetic biology for the development of technologically advanced biological sensors. They worked with Australian colleagues in designing, building, and testing Acinetobacter bayliyi as a sensor to identify DNA from KRAS gene which is mutated in many cancers.

Experts previously design bacteria to perform different diagnostic and therapeutic functions, but they lack the ability to detect specific DNA sequences and mutations outside of cells. To address this challenge, the research team designed a technology called "Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer" or CATCH.

The project started four years ago without assurance that bacteria can be used as a sensor for mammalian DNA, according to scientific team leader Professor Jeff Hasty. However, they realized that this invention can be applied in detecting gastrointestinal cancers and precancerous lesions.

Cancer cells are known to disperse their DNA into the environment. Current technologies can effectively analyze purified DNA in the laboratory but find it difficult to detect DNA on the spot where it was released. Using the CATCH method, Hasty and his team engineered bacteria to analyze free-floating DNA sequences on a genomic level and compared the samples with predetermined cancer sequences.

The research was based on horizontal gene transfer which is widely used by bacteria in moving their genetic material between one another. This method inspired the researchers to apply the concept of transferring genome from mammalian tumors and human cells into bacteria.

The Acinetobacter bayliyi bacterium was programmed with a CRISPR system designed to distinguish mutated from non-mutated copies of KRAS. The mutant forms of KRAS are found in precancerous polyps and cancers, and only the bacteria that had taken up these copies would survive to respond to the disease.

Scientists are hopeful that engineered bacteria offer potential in preventing colorectal cancer which ranks as the fourth most common cancer in both men and women. In the future, they plan to adapt their bacterial biosensor to treat various forms of human cancers and infections.

Horizontal Gene Transfer in Bacteria

Gene transfer refers to the process of passing the genes from one cell to another. It can be done vertically when a cell replicates its DNA and is passed down from parents to offspring. In horizontal gene transfer, the genetic material moves across distantly related organisms without the need for mating.

Horizontal gene transfer is common among microorganisms. There are certain bacteria that can retrieve cell-free DNA found in their environment. The free-floating DNA is the genetic material released when a cell dies.

Bacteria can absorb these DNA in a phenomenon called natural competence which plays an important role in their evolution. For instance, the transfer of antibiotic-resistance genes (ARGs) influences the development of multidrug resistance (MDR) in bacteria.