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 Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>