For
the first time UK scientists have shown what the food poisoning
bug Salmonella feeds on to survive as it causes infection: glucose.
Their
discovery of Salmonellas weakness for sugar could provide
a new way to vaccinate against it. The discovery could also lead
to vaccine strains to protect against other disease-causing bacteria,
including superbugs.
This
is the first time that anyone has identified the nutrients that
sustain Salmonella while it is infecting a hosts body,
says Dr Arthur Thompson from the Institute of Food Research.
The
nutrition of bacteria during infection is an emerging science. This
is one of the first major breakthroughs, achieved in collaboration
with Dr. Gary Rowley at the University of East Anglia.
Salmonella
food poisoning causes infection in around 20 million people worldwide
each year and is responsible for about 200,000 human deaths. It
also infects farm animals and attaches to salad vegetables.
During
infection, Salmonella bacteria are engulfed by immune cells designed
to kill them. But instead the bacteria multiply.
Salmonella
must acquire nutrients to replicate. The scientists focused on glycolysis,
the process by which sugars are broken down to create chemical energy.
They constructed Salmonella mutants unable to transport glucose
into the immune cells they occupy and unable to use glucose as food.
These mutant strains lost their ability to replicate within immune
cells, rendering them harmless
Our
experiments showed that glucose is the major sugar used by Salmonella
during infection, said Dr Thompson.
The
mutant strains still stimulate the immune system, and the scientists
have filed patents on them which could be used to develop vaccines
to protect people and animals against poisoning by fully virulent
salmonella.
Glycolysis
occurs in most organisms including other bacteria that occupy host
cells. Disrupting how the bacteria metabolise glucose could therefore
be used to create vaccine strains for other pathogenic bacteria,
including superbugs.
The
harmless strains could also be used as vaccine vectors. For example,
the flu gene could be expressed within the harmless Salmonella strain
and safely delivered to the immune system.
The
next stage of the research will be to test whether the mutants elicit
a protective immune response in mice.
In
Germany the nutrition of bacteria is the subject of a six-year priority
programme of research to investigate why bacteria are able to multiply
inside a hosts body to cause disease.
The
IFR is an institute of the Biotechnology and Biological Sciences
Research Council (BBSRC). This research was funded by a Core Strategic
Grant from BBSRC.
Full
reference: Glucose and glycolysis are required for the successful
infection of macrophages and mice by Salmonella enterica serovar
Typhimurium Steven D. Bowden, Gary Rowley, Jay C.D. Hinton, and
Arthur Thompson Infect. Immun. published 20 April 2009, 10.1128/IAI.00093-09
http://iai.asm.org/cgi/content/abstract/IAI.00093-09v1
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