Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sequence provides insights into a pathogen’s virulence mechanism allowing for vaccine development

27.08.2002


Scientists have analyzed the complete genome sequence of an emerging human pathogen, Streptococcus agalactiae (also known as group B streptococcus or "strep B"), which is a leading cause of pneumonia and meningitis in newborns and the source of life-threatening illnesses in a growing number of adults with deficient immune systems.



The study, published this week in the on-line version of the Proceedings of the National Academy of Sciences (PNAS), not only determined the pathogen’s genetic makeup but also compared it to other isolates of the same microbe. That analysis shed light onto why S. agalactiae -- which is found in the digestive or genital tracts of many healthy people – has emerged in recent years as a more widespread and virulent cause of illness in certain adults.

"We were surprised to find so many differences among the isolates of this important pathogen," said Hervé Tettelin, an associate investigator at The Institute for Genomic Research (TIGR) who led the sequencing project. "Those differences could help explain why some strains of S. agalactiae are much more virulent than others."


Tettelin and other TIGR scientists did the comparative genomics analysis in cooperation with a research group led by Dennis L. Kasper at Harvard Medical School and a team led by Guido Grandi at the vaccine research division of Chiron, S.p.A., a biomedical company that funded the research project. The research was supported by Chiron and by grants from the National Institutes of Health.

"Completion of the genome sequence represents an important milestone in the study of this organism," said Kasper. "We anticipate that many investigators will take advantage of the S. agalactiae genome sequence to identify new virulence determinants and potential targets for vaccine development."

"We wanted the genome information to identify proteins which can be used in a vaccine," said Guido Grandi, head of Biochemistry and Molecular Biology at Chiron vaccine research. "We have used this new genomic approach already to make a type B meningococcal meningitis vaccine which is now being tested in people. So we know that the strategy works."

To find out more about the molecular reasons for the virulence of what is known as the "serotype V" isolate of S. agalactiae, the authors of the study compared that genome to the genetic makeup of other S. agalactiae strains and also with two different species of streptococci that cause human diseases: S. pneumoniae, which causes pneumonia, meningitis and septicemia, and S. pyogenes, which among other illnesses causes the "strep throat" that can lead to acute rheumatic fever.

Tettelin said the microarray experiments that compared those related genomes found numerous differences, even among strains with the same serotype – that is, the type of polysaccharides that make up the capsule (outer coat) that surrounds each bacterium. The genetic diversity indicates that S. agalactiae has mechanisms (including acquisition, duplication and re-assortment of genes) that have allowed it "to adapt to new environmental niches and to emerge as a major human pathogen."

They also said in silico (computer) analysis showed that S. agalactiae’s genome differed from that of other streptococci in several of the microbe’s metabolic pathways and in related transport systems through the bacterium’s cell membrane. Those differences probably relate to how S. agalactiae adapted to distinct niches in its human and bovine hosts, the paper suggests. The researchers also found genes unique to S. agalactiae that likely play a role in colonization or in disease: genes related to surface proteins, capsule synthesis, and the hemolysin enzyme that clears the path for microbes to invade other parts of the body and cause disease.

The researchers chose to sequence type V because it is the most common capsule type that is associated with invasive infection among adults other than pregnant women. And the emergence of type V strains over the last decade appears to parallel the increase in S. algalactiae-related diseases among those adults.

While S. agalactiae is normally a harmless organism when it colonizes the human gastrointestinal or genital tracts, the microbe can cause life-threatening invasive infection in susceptible hosts, which include newborn infants, pregnant women, and adults with underlying chronic illnesses. The number of neonatal S. agalactiae infections has dropped since physicians began prescribing antibiotics during delivery for high-risk pregnant women in 1996, but invasive infections in adults with deficient immune systems have increased.

S. agalactiae has a circular genome of about 2.16 million base pairs. Researchers predicted that there are 2,176 genes in that genome, and about 65% of the proteins expressed by those genes were of known function. The authors of the study found that the three streptococcal species shared 1,060 genes--about half of their genes-- but that 683 genes are unique to S. agalactiae.

"This study is important because it sheds light on the virulence mechanism of one of the last major human pathogens whose genome had not yet been sequenced," said Claire M. Fraser, TIGR’s president. "This should help researchers find vaccine candidates or drug targets to fight a pathogen with broad impact on human health."

Debbie Lebkicher | EurekAlert!
Further information:
http://www.tigr.org/

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>