A new mechanism for a bacterial toxin to inhibit inflammation in a commonly inherited autoinflammatory disease has been discovered by scientists.
The study showed that a toxin in Yersinia pestis, which is the bacterial agent of plague, targets and inhibits the protein pyrin.
"This finding is very significant because it may explain the natural selection process behind a chronic condition that affects a high prevalence of people originating around the Mediterranean Sea," said lead author James Bliska, Professor at the Stony Brook University in New York, US.
‘Toxin in Yersinia pestis targets and inhibits pyrin protein which is linked to Familial Mediterranean fever. Familial Mediterranean fever is a hereditary inflammatory disorder caused by mutations in MEFV -- a gene that leads to continuous activation of a protein called pyrin -- causing problems in regulating inflammation in the body.
Thousands of individuals from many ethnic origins of the Mediterranean, such as Armenians, Italians, Greeks and Arabs have FMF, the study said.
In addition, the bacterial toxin hijacks human kinases to phosphorylate and inhibits pyrin, a process that could be translated into therapeutics for FMF, Bliska added.
The hereditary inflammatory disease of FMF usually strikes individuals at some point in childhood and continues throughout adulthood.
They occur in bouts called attacks that last one to three days. Arthritic attacks may last for weeks or months.
Fever, abdominal pain, chest pain, achy, swollen joints, constipation followed by diarrhea, a red rash on legs, especially below the knees, muscle aches, a swollen, tender scrotum, include the signs and symptoms of FMF.
There are treatments but no cures, and complications such as arthritis and vasculitis can occur after many prolonged inflammatory episodes.
The findings, published in Cell Host & Microbe, can be used to better understand the genetic origins of FMF and explore new therapies for the disease.