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 New mechanisms uncovered explaining frost tolerance in plants
26.09.2016 | Technische Universität München

nachricht Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Stronger turbine blades with molybdenum silicides

26.09.2016 | Materials Sciences

Scientists Find Twisting 3-D Raceway for Electrons in Nanoscale Crystal Slices

26.09.2016 | Materials Sciences

Lowering the Heat Makes New Materials Possible While Saving Energy

26.09.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>