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."
Don Powell | alfa
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy