Navigation Links
Defining DNA differences to track and tackle typhoid
Date:7/27/2008

For the first time, next-generation DNA sequencing technologies have been turned on typhoid fever - a disease that kills 600,000 people each year. The results will help to improve diagnosis, tracking of disease spread and could help to design new strategies for vaccination.

The study sets a new standard for analysing the evolution and spread of a disease-causing bacterium: it is the first study of multiple samples of any bacterial pathogen at this level of detail. It uncovers previously hidden genetic signatures of the evolution of individual lineages of Salmonella Typhi.

The team developed methods that are being used to type outbreaks, allowing researchers to identify individual organisms that are spreading in the population: using Google Earth, the outbreaks can be easily visualized. The team hope that these mapping data can be used to target vaccination campaigns more successfully with the aim of eradicating typhoid fever.

Unlike most related Salmonella species, and in contrast to many other bacteria, Typhi is found only in humans and the genomes of all isolates are superficially extremely similar, hampering attempts to track infections or to type more prevalent variants. The detail of the new study transforms the ability of researchers to tackle Typhi.

"Modern genomic methods can be used to develop answers to diseases that have plagued humans for many years," explains Professor Gordon Dougan from the Wellcome Trust Sanger Institute and senior author on the study. "Genomes are a legacy of an organism's existence, indicating the paths it has taken and the route it is on. This analysis suggests we may have found Typhi's Achilles' heel: in adapting to an exclusively human lifestyle, it has become complacent, its genome is undergoing genetic decay and it's heading up an evolutionary dead end in humans.

"We believe that concerted vaccination programmes, combined with epidemiological studies aiming to track down and treat carriers, could be used to eradicate typhoid as a disease."

There are 17 million cases of Typhoid fever each year - although the World Health Organization cautions that this is a 'very conservative' estimate. Young people are most at risk: in Indonesia, nine out of ten cases occur in 3-19-year-olds.

"A key to survival of Salmonella Typhi is its ability to lie dormant in carriers, who show no symptoms but remain able to infect others," says Kathryn Holt, a PhD student at the Wellcome Trust Sanger Institute and first author on the study. "Our new tools will assist us in tracing the source of typhoid outbreaks, potentially even to infected carriers, allowing those individuals to be treated to prevent further spread of the disease.

"Using the genomic biology of this study, we can now type Typhi, identify the strain that is causing infection, identify carriers and direct vaccination programmes most efficiently. It is a remarkable step forward."

The study is a collaboration between researchers at the Wellcome Trust Sanger Institute, University College, Cork, Institut Pasteur in Paris and Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. The team studied 19 isolates of Typhi from ten countries, using new sequencing methods that meant they could capture the rare signals of genetic variation in this stubborn genome. They produced more than 1.7 billion letters of genetic sequence and found evidence of fewer than 2000 mutation events, suggesting very little evolution since the emergence of Typhi at least 15,000 years ago.

Their analysis shows that the Typhi genome is decaying - as it becomes more closely allied to us, its human host, it is losing genes that are superfluous to life in the human body. More importantly, genes that contain instructions for the proteins on the surface of the bacterium - those most often attacked by our immune system defences - vary much less than do the equivalent genes in most other bacteria, suggesting that Typhi has a strategy to circumvent the selective pressures of our immune system.

"Both the genome and the proteins that make up the surface of Typhi - the targets for vaccines - show amazingly little variation," says Professor Julian Parkhill, Head of Pathogen Genomics. "We have been able to use novel technologies, developed for the analysis of human genome variation, to identify this variation: this would have been impossible a year ago. The technologies we have developed here could also be used in the battles against other disease-causing bacteria."


'/>"/>

Contact: Don Powell
don@sanger.ac.uk
44-012-234-96928
Wellcome Trust Sanger Institute
Source:Eurekalert

Related biology news :

1. Defining genes role may lead to prevention of dangerous corn toxin
2. Negligent, attentive mouse mothers show biological differences
3. Sex differences in the brains serotonin system
4. Tiny genetic differences have huge consequences: McGill researchers
5. Worms take the sniff test to reveal sex differences in brain
6. Analysis of breast and colon cancer genes finds many areas of differences between tumors
7. Genetic differences in clover make one type toxic
8. Claims of sex-related differences in genetic association studies often not properly validated
9. St. Jude influenza survey uncovers key differences between bird flu and human flu
10. Tracking prions
11. Scientists paint viruses to track their fate in the body
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/19/2017)... , April 19, 2017 The ... vendor landscape is marked by the presence of several ... however held by five major players - 3M Cogent, ... companies accounted for nearly 61% of the global military ... companies in the global military biometrics market boast global ...
(Date:4/11/2017)... Fla. , April 11, 2017 ... and secure authentication solutions, today announced that it ... Intelligence Advanced Research Projects Activity (IARPA) to develop ... Thor program. "Innovation has been a ... IARPA,s Thor program will allow us to innovate ...
(Date:4/5/2017)... Allen Institute for Cell Science today announces the launch ... dynamic digital window into the human cell. The website ... deep learning to create predictive models of cell organization, ... suite of powerful tools. The Allen Cell Explorer will ... resources created and shared by the Allen Institute for ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... ... States multicenter, prospective clinical study that demonstrates the accuracy of the FebriDx® ... identifying clinically significant acute bacterial and viral respiratory tract infections by testing ...
(Date:10/11/2017)... ... October 11, 2017 , ... At its national board ... Suneel I. Sheikh, the co-founder, CEO and chief research scientist of Minnesota-based Advanced ... for membership in ARCS Alumni Hall of Fame . ASTER Labs is ...
(Date:10/11/2017)... (PRWEB) , ... October 11, 2017 , ... ... pathology, announced today it will be hosting a Webinar titled, “Pathology is going ... Pathology Associates , on digital pathology adoption best practices and how Proscia improves ...
(Date:10/11/2017)... ... October 11, 2017 , ... A new study published ... frozen and fresh in vitro fertilization (IVF) transfer cycles. The multi-center ... success. , After comparing the results from the fresh and frozen transfer cohorts, ...
Breaking Biology Technology: