New insights into Chlamydial Infection

Genome decoded of sheep pathogen

New insights into Chlamydial Infection

genome.jpg
Circular representation of the C. abortus chromosome. From the outside in, circles 1 and 2 show the position of genes transcribed in a clockwise and anticlockwise direction, respectively; circles 3 and 4 CDS encoding all membrane proteins (green) minus the Pmp and TMH/Inc family proteins in the clockwise and anticlockwise directions, respectively; circles 5 and 6 show members of the Pmp (pink) and TMH/Inc protein families (blue) in the clockwise and anticlockwise directions, respectively. Circle 7 shows a plot of G+C content (in a 10-kb window); circle 8 shows a plot of GC skew ([G^AC]/[G+C]; in a 10-kb window)

It is spring time, and the idyllic image is of new-born lambs and their mothers feasting on lush pastures. But a potential killer lurks in the grass.

Today, the hiding places for that killer - a bacterium called Chlamydophila abortus - are fewer because of the genome sequence produced in a collaboration between the Wellcome Trust Sanger Institute, the Moredun Research Institute and the Scottish Crop Research Institute.

Infection with Chlamydophila abortus is the most common cause of infectious abortion in sheep in the UK, leading to loss of lambs and economic costs of around £30M each year. Chlamydial infections of humans and animals are of enormous public and animal health significance worldwide, both in terms of disease and economic impact.

The genome sequence, published in Genome Research, will bring new possibilities in the fight to control the spread of infection.

"Genomics has transformed this field because we had a complete lack of genetic tools for research directed at combating chlamydial disease. Comparing this genome with those of other chlamydial species sequenced to date and others that are in progress will help to identify proteins for vaccine development and for the development of specific diagnostic tests."

Dr David Longbottom, Head of Molecular Chlamydia Research at the Moredun Research Institute

Infection in domestic animals is thought to be through ingestion of bacteria deposited on the grass via infected placentas after birth. Although there are commercially available vaccines, the disease persists because of difficulties in diagnosis, in vaccine uptake and in management of the sheep flocks. Early diagnosis is important and the infection responds well to early treatment with antibiotics, particularly tetracyclines and erythromycin. The newly produced sequence will help in the identification of suitable targets for improving diagnosis and will aid vaccine development.

"The genome is very similar to the genome of the related organisms C. pneumoniae and C. caviae. However, we have identified variable families of proteins which will be key genes to study in the disease process and for intervention."

Dr Nick Thomson, Project Leader at the Wellcome Trust Sanger Institute

The genome paper describes the identification and characterisation of these proteins, which will form the basis for future research. The finished and annotated sequence consists of 1,144,377 base-pairs and codes for a predicted 961 proteins. The low number of genes suggests that the genome of C. abortus has been modified for a specific niche: as an intracellular infection, it can lay dormant between outbreaks and cause abortion of lambs in a following season. Individual animals carry the infection asymptomatically.

Especially with the coming of spring and lambing season, C. abortus also becomes a potential threat to human health: pregnant women exposed to infected animals are at possible risk of abortion and life-threatening illness. Most farms advise pregnant women not to come in contact with pregnant sheep or their lambs.

"We expect to see improvements in the development of new vaccines and diagnostic tests. Together with combined changes in flock management practices, these will ultimately reduce the environmental spread of infection to other animals and reduce the risks of zoonotic transmission to humans."Dr David Longbottom, Head of Molecular Chlamydia Research at the Moredun Research Institute

Chlamydophila abortus is part of a family of bacteria that includes Chlamydia trachomatis, the most common sexually transmitted pathogen in the United Kingdom. It is an obligate intracellular organism - one that can divide only within a host cell. Inside the host cell, the bacteria develop in a specialized 'compartment' called an inclusion. This makes these organisms very difficult to study in the laboratory. The information gained from the genome sequence combined with that from the other chlamydial genomes will ultimately enable advances in research to address key questions on how these organisms cause disease.

Notes to Editors
Publications
  • The Chlamydophila abortus genome sequence reveals an array of variable proteins that contribute to interspecies variation.

    Thomson NR, Yeats C, Bell K, Holden MT, Bentley SD et al.

    Genome research 2005;15;5;629-40

Funding

This two-year collaborative project was funded by the Scottish Executive Environment and Rural Affairs Department (SEERAD) and ended in March 2004. The Pathogen Sequencing Unit and Pfam Group are supported by the Wellcome Trust.

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