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Press Releases: 14th September 2004
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Burkholderia
pseudomallei, the causative agent of melioidosis.
Copyright Dennis Kunkel Microscopy,
Inc. |
Getting a Grip on the Great Mimicker
Secrets of a Stealth Organism
For a doctor it is all about signs - the clues to a disease lie in
how the patient feels, where it hurts and what is affected. For many
diseases, diagnosis can be swift and sure.
But what happens when we are infected by an organism that can
strike anywhere, at any time and cause almost any symptom? Diagnosis
is denied.
Living amongst the roots of tropical plants is a soil bacterium
with the unwieldy name Burkholderia pseudomallei - or often
'The Great Mimicker'. This organism can cause blood disease,
abscesses, lung disease, kidney disease, heart disease and more. In
some areas of the world, half of teenagers with blood infections
die. Sometimes it lays dormant for years before striking.
The disease is called melioidosis and this week researchers from
The Wellcome Trust Sanger Institute and colleagues in Thailand,
Australia and the US report the analysis of the genome of
Burkholderia pseudomallei in the journal Proceedings
of the National Academy of Sciences USA.
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B. pseudomallei cells
(stained red) escaping from cells using actin
"rockets".
Image provided
by Mark Stevens and Edouard Galyov, Institute of Animal Health,
Compton. |
Remarkably, it has two large chromosomes (most bacteria have one)
and the two have broadly different roles. The larger contains genes
for most of the 'housekeeping' work of the cell, whereas the smaller
contains genes that allow B. pseudomallei to adapt and
survive.
Explaining the significance of this organism, Dr Julian Parkhill,
Project manager at the Sanger Institute, said: "This research emphasises the diversity and
adaptability of bacteria. Human beings are merely one of the diverse
niches in which this remarkable organism can
thrive."
Melioidosis is one of the emerging infectious diseases - part of
our never-ending struggle to deal with bacteria that acquire new
weapons to infect humans. For B. pseudomallei, the genome
structure shows that both chromosomes have acquired whole new
regions of DNA (genomic 'islands'), gaining new sets of genes to
help the organism to live in humans and other environments. And,
with double the amount of DNA in a 'typical' bacterium,
B. pseudomallei is one of the most adaptable.
Dr Matthew Holden, who headed the analysis of the B. pseudomallei
genome, said: "B. pseudomallei is a
formidable pathogen, with a genome to match. The size and ability to
acquire new genes ensures that is well equipped for action, what
ever the conditions."
As well as being an emerging organism, B. pseudomallei has
been listed as a potential bioweapon, because of its potential to
cause disease after inhalation. The most common route of infection,
however, is through open wounds or abrasions from contaminated
soils. The organism can also infect many other animals including
sheep, pigs, cattle and birds.
With the genome sequence to hand, new methods can be developed to
detect and diagnose the infection, as well as to investigate
possible targets for new vaccines. B. pseudomallei is
intrinsically resistant to many antibiotics and treatment normally
relies on a combination of antibiotics over more than one month.
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Notes to Editors
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Transmission electron micrograph of B. pseudomallei with
flagella.
Image provided by Sharon Peacock, University of Oxford. |
- About melioidosis
- The causative organism of melioidosis was first described in
Burma in 1911 by the British pathologist Captain A. Whitmore: the
disease was originally called Whitmore disease.
- Melioidosis is a serious disease of humans and animals that
occurs primarily in SE Asia, N Australia and other tropical
areas. It is thought that 10-25% of people in endemic areas
may be infected but remain asymptomatic. There is no licensed
vaccine, and the bacterium is resistant to many antibiotics.
- The bacterium is a soil-dwelling organism and usually infects
humans through open wounds or abrasions through contact with
contaminated soil. It can also infect a wide range of animals.
- Infection is particularly severe in people whose immune system
is impaired, such as those with other diseases (diabetes, lung
disease). About 40-50% of those with septicaemia die.
- The organism can lie dormant for decades and only cause overt
symptoms when the person infected is weakened. An estimated
225,000 Vietnam veterans are positive for signs of melioidosis.
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B. pseudomallei cells
(small dots) escaping from fused macrophage cells (cell nuclei are
piled on one another in centre).
Image
provided by Nat Brown, Griffith University-Gold Coast
Campus. |
- Publication details
Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei.
Holden MT, Titball RW, Peacock SJ, Cerdeno-Trraga AM, Atkins T, Crossman LC, Pitt T, Churcher C, Mungall K, Bentley SD, Sebaihia M, Thomson NR, Bason N, Beacham IR, Brooks K, Brown KA, Brown NF, Challis GL, Cherevach I, Chillingworth T, Cronin A, Crossett B, Davis P, DeShazer D, Feltwell T, Fraser A, Hance Z, Hauser H, Holroyd S, Jagels K, Keith KE, Maddison M, Moule S, Price C, Quail MA, Rabbinowitsch E, Rutherford K, Sanders M, Simmonds M, Songsivilai S, Stevens K, Tumapa S, Vesaratchavest M, Whitehead S, Yeats C, Barrell BG, Oyston PC, Parkhill J
Proc Natl Acad Sci U S A. 2004;. PMID: 15377794
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