Researchers have discovered a mechanism that kills intestinal
worms, which affect nearly a third of the world's population as
well as livestock. The findings, published in Cell Host &
Microbe, could help scientists create new vaccines or drugs to
combat intestinal worm infections.
The worm-killer is an enzyme that is thought to disrupt vital
cell processes in intestinal worms. Although scientists have
previously known how worms are expelled from the body through the
gut, this is the first time that a mechanism of worm killing has
been discovered.
"If we can figure out how the enzyme is regulated, increasing
the amount may promote immunity to intestinal worms," says Lewis
Entwistle, first author of the paper and researcher at the Francis
Crick Institute.
The research was led by the Francis Crick Institute, in
collaboration with the London School of Hygiene and Tropical
Medicine, the University of Cincinnati College of Medicine, and
Genentech Inc.
The team first suspected that this enzyme might have a role in
killing intestinal worms when mice that are immune to worm
infections were found to have sustained high levels of the
enzyme.
When they knocked out the gene in mice, so that they didn't make
the enzyme, intestinal worms were not killed and expelled from the
body as normal. But when they pre-treated worms with the enzyme
before infection, killing and expulsion from the mice was
restored.
Mark Wilson, senior author of the paper and Group leader at the
Francis Crick Institute, says: "Building up the armory is
pointless, without the right bullet. The immune system certainly
plays a role in getting rid of intestinal worms, but this enzyme is
the 'bullet' that kills them.
"There is an emerging problem of drug-resistant worms, and a
need for better vaccines against them. Our findings provide a new
avenue for developing novel drugs and vaccines, to combat the
infections."
To find out how the enzyme kills intestinal worms, the team
compared enzyme-treated worms with controls. Chemical analysis
revealed that enzyme-treated worms had fewer phospholipids -
molecules in cell membranes that are required for many crucial
processes.
"Designing drugs that mimic the effect of the enzyme on
intestinal worms could also be a fruitful avenue for combating worm
infections," says Lewis.
The paper 'Epithelial cell-derived phospholipase A2 group 1B
(PLA2g1B) is an endogenous anthelmintic' is published inCell Host & Microbe.