How the typhoid toxin works to hijack DNA repair machines and accelerate the aging of cells has been elucidated, a breakthrough that could pave the way for new strategies to combat the killer disease, according to a team from the University of Sheffield.
To cause typhoid, the bacterial pathogen Salmonella typhi releases the typhoid toxin, which damages cellular DNA. Our DNA is constantly under threat by environmental factors, but cells usually have robust DNA repair machines to combat these threats. In the case of the typhoid toxin attacking our cells, it is this repair machine function that gets hijacked. First author Angela Ibler who made the discovery dubbed the DNA damage response RING—response induced by a genotoxin—in reference to the single-strand breaks in the double helix of human cell DNA that accumulate in a signature ring-like pattern.
The findings, published in Nature Communications today could potentially enable the toxin-associated cellular aging to be used as a biomarker to help with earlier diagnosis and faster treatment for typhoid sufferers.
"Our findings have shown that pathogenic bacteria can speed up cellular aging through a toxin and take advantage of this to establish infections. This makes sense as infections are often harder to combat and recover from as we get old, which is partly due to cellular aging, but the fact that bacterial pathogens target this phenomenon is unexpected,” explained senior author Daniel Humphreys.
Image: RINGs of DNA damage in human cells caused by the typhoid toxin underlying typhoid fever. Image courtesy of University of Sheffield.