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 Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>