Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How pathogenic bacteria prepare a sticky adhesion protein

09.04.2018

Researchers at Harvard Medical School, the University of California, San Francisco, and the University of Georgia have described how the protein that allows strep and staph bacteria to stick to human cells is prepared and packaged. The research, which could facilitate the development of new antibiotics, will appear in the April 6 issue of the Journal of Biological Chemistry.

All bacteria have a standard secretion system that allows them to export different types of proteins outside of their cells. An important class of extracellular molecules produced by pathogenic bacteria are adhesins, proteins that enable bacteria to adhere to host cells. For unknown reasons, the SRR (serine-rich-repeat) adhesins of Staphylococcus and Streptococcus bacteria - pathogens that can be involved in serious infections such as bacterial meningitis, bacterial pneumonia and pericarditis - are transported through a secretion pathway that is similar to the standard system, but dedicated solely to adhesin.


Pathogenic gram-positive bacteria, such as S. gordonii, export a serine-rich adhesin to facilitate their attachment to host cells. Adhesin uses a dedicated secretion pathway, with several steps occurring in the cytosol before its translocation across the membrane. The adhesin GspB (shown in red) is first modified by N-acetylglucosamine (orange hexagon) and glucose (wheat hexagon) in a strictly sequential order. It is then targeted to the membrane by a complex of three accessory secretion proteins (Asp 1-3; shown in green, blue, and pink), two of which resemble carbohydrate-binding proteins (crystals structures are shown ribbon diagrams imbedded in space-filling presentation). Finally, GspB adhesin is moved through the membrane by a dedicated ATPase (SecA2) and membrane channel (SecY2) (both shown in cyan).

Credit: Yu Chen, Harvard Medical School

It would be as if a warehouse that processes many types of goods were to have a separate set of doors and forklifts for just one of its wares. Tom Rapoport, a professor at Harvard Medical School who oversaw the new study, wanted to understand what exactly these dedicated molecular supply chains were doing.

"I was intrigued by the fact that there is a second secretion system in some bacteria that is separate from the canonical secretion system and is just dedicated to the secretion of one protein," Rapoport said. "There is a whole machinery, and it's only doing one thing."

Yu Chen, at the time a postdoctoral research associate in Rapoport's lab, led the investigation. She found that, in order to be transported, the adhesin protein needed to be modified with specific sugars by three enzymes acting in a specific sequence. These sugar modifications stabilize the protein and enhance its stickiness to target cells.

Furthermore, the experiments showed that two proteins in the adhesin-specific pathway, whose function had previously been mysterious, seemed to be able to bind to these sugars, presumably enabling them to carry the adhesin to the cell membrane where adhesin's dedicated exit channel is located.

The complexity of the adhesin transport system necessitated collaboration with research teams at UCSF, Harvard Medical School, and the University of Georgia. Members of Paul Sullam's lab at UCSF provided the clinical perspective, members of Maofu Liao's lab at Harvard characterized the targeting complex by electron microscopy, and members of Parastoo Azadi's lab at Georgia analyzed the sugar modifications.

"It's a complicated system because it involves protein modification, chaperone activity and membrane targeting, so we encountered a lot of challenges," Chen said. "This (study) is a great example of how collaboration across labs in the scientific community advances human knowledge."

The reason that these bacteria use this separate export pathway for adhesins remains elusive. But because this pathway is unique to strep and staph bacteria, the new understanding of its components could help researchers develop highly targeted antibiotics to treat infections caused by these bacteria in the future.

"You could imagine that you could develop novel antibiotics that could target this pathway," Rapoport said. "(They) would be very specific for pathogenic bacteria."

###

The work was funded by the National Institutes of Health, the U.S. Department of Energy and the Howard Hughes Medical Institute.

About the Journal of Biological Chemistry

JBC is a weekly peer-reviewed scientific journal that publishes research "motivated by biology, enabled by chemistry" across all areas of biochemistry and molecular biology. The read the latest research in JBC, visit http://www.jbc.org/.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions. For more information about ASBMB, visit http://www.asbmb.org.

Media Contact

Alexandra Mushegian
amushegian@asbmb.org
240-283-6616

 @asbmb

http://www.asbmb.org 

Alexandra Mushegian | EurekAlert!

Further reports about: Biochemistry Biology Harvard JBC Molecular Biology antibiotics pathogenic bacteria proteins

More articles from Life Sciences:

nachricht Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo

nachricht Full of hot air and proud of it
18.04.2018 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

Im Focus: Stronger evidence for a weaker Atlantic overturning

The Atlantic overturning – one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards – is weaker today than any time before in more than 1000 years. Sea surface temperature data analysis provides new evidence that this major ocean circulation has slowed down by roughly 15 percent since the middle of the 20th century, according to a study published in the highly renowned journal Nature by an international team of scientists. Human-made climate change is a prime suspect for these worrying observations.

“We detected a specific pattern of ocean cooling south of Greenland and unusual warming off the US coast – which is highly characteristic for a slowdown of the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Improved stability of plastic light-emitting diodes

19.04.2018 | Power and Electrical Engineering

Enduring cold temperatures alters fat cell epigenetics

19.04.2018 | Life Sciences

New capabilities at NSLS-II set to advance materials science

18.04.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>