Francis Crick Institute scientists
have validated a mouse model of a human disease called melioidosis,
using bioinformatics to confirm that many of the same molecular
biological processes occur in mice as humans.
The work has also provided some new
insights into this often severe infection, for which there is
currently no vaccine and which can be difficult to treat with
antibiotics.
Melioidosis can present in many
different ways in humans - from acute blood poisoning, with
death rates of up to 40%, to chronic localised infection or
even dormant disease. It is caused by a bacteria that is found in
tropical locations, particularly in SE Asia and Northern Australia,
but is being increasingly reported in other tropical countries.
It is spread through direct contact with contaminated water
and soil and people with diabetes in these countries are
particularly at risk of infection.
Dr O'Garra (currently based at Mill
Hill) said: "Mouse models have been widely used to study infections
and to test new therapies or vaccines. However in human melioidosis
it's not known how faithfully such mouse models of the disease
mimic its biology at a molecular level."
In this study the team compared all
the genes over or under-expressed in tissue and blood samples from
mice as a result of infection with B. pseudomallei, the bacteria
that causes melioidosis. They compared this to the blood gene
expression profiles of patients with acute melioidosis in North
East Thailand.
The results showed that the blood
gene expression profile in mice infected with B. pseudomallei
accurately reflects the disease severity in animals with latent,
acute and chronic infections and showed strong similarities among
key host immune defence processes to those observed in human
patients.
Dr O'Garra said: "Our data not only
provide new information on the disease process of this infection
but also demonstrate that a complementary set of bioinformatics
approaches can provide valuable insights into the response pathways
that are similar in mice and humans.
"This approach can therefore be
used to validate mouse models of human disease and lead to ways to
improve these."
The paper, The Blood Transcriptome of Experimental Melioidosis Reflects
Disease Severity and Shows Considerable Similarity with the Human
Disease, is published in the Journal of
Immunology.