Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Protein that Delays Cell Division in Bacteria may Lead to the Identification of New Antibiotics

Published: Thursday, August 15, 2013
Last Updated: Thursday, August 15, 2013
Bookmark and Share
Scientists have worked out how two bacterial strains delay cell division when food is abundant.

In 1958 a group of scientists working in Denmark made the striking observation that bacterial cells are about twice as large when they are cultured on a rich nutrient source than when they are cultured on a meager one. When they are shifted from a nutrient-poor environment to a nutrient-rich one, they bulk up until they have achieved a size more appropriate to their new growth conditions.

It has taken 60 years to figure out how the bacteria are able to sample their surroundings and alter their cell cycles so that they grow to a size suited to the environment.

In 2007 Petra Levin, PhD, a biologist at Washington University in St. Louis, reported in Cell that a soil bacterium named Bacillis subtilis has a protein that senses how much food is available and, when food is plentiful, temporarily blocks the assembly of a constriction ring that pinches a cell in two to create two daughter cells.

Now Norbert Hill, a graduate student in her group, reports in the July 25 online edition of PLoS Genetics that Escherichia coli uses a similar protein to help ensure cell size is coordinated with nutrient conditions.

Delaying division even just a little bit leads to an increase in daughter cell size. Once stabilized at the new size, cells take advantage of abundant nutrient sources to increase and multiply, doubling their population at regular intervals until the food is exhausted.

Because both the B. subtilis and E. coli proteins interact with essential components of the division machinery, understanding how they function will help in the discovery of antibiotics that block cell division permanently. A group in Cambridge, England, is already working to crystallize the E. coli protein docked on one of the essential components of the constriction ring.

If they are successful they may be able to see exactly how the protein interferes with the ring’s assembly. An antibiotic could then be designed that would use the same mechanism to prevent division entirely, killing the bacteria.

Why do bacteria get bigger on a good food source?

Bacteria increase and multiply by a process called binary fission. Each cell grows and then the divides in the middle to produce two daughter cells. What could be simpler?

But the closer you look, the less simple it becomes. For binary fission to work the cell must make a copy of its circular chromosome, unlink and separate the two chromosomes to create a gap between them, assemble a constriction ring in the middle of the cell and coordinate the growth of new cell membrane as the ring cinches tight and pinches the mother cell in two. To complicate matters, bacteria don’t necessarily do these steps one by one but can instead work on several steps simultaneously.

Most of the time the goal is to produce daughters the same size as the mother cell. But when food is plentiful, bacteria start making more copies of their DNA (as many as 12) in anticipation of divisions to come, and they can’t easily cram all the extra DNA into standard-sized cells. So they grow bigger to accommodate the extra genetic material and remain large as long as the food lasts.

The inventory of partly copied chromosomes fuels rapid population growth, because a cell doesn’t start from scratch when it needs another copy of its chromosome. Under optimum conditions, E. coli, for example, divides once every 17 minutes. If they are allowed to grow unhindered this means that in 24 hours 1 bacterium becomes about 5 x 1021 bacteria (that is 5 with 21 zeros after it.)

How do bacteria know the pickings are rich?

In B. subtilis and E. coli the signal is a modified sugar called UDP-glucose. Presumably, the richer the growth medium, the higher the level of this sugar inside the cell.

In both bacteria UDP-glucose binds to a protein and the sugar-protein complex then interferes with the assembly of the constriction ring. In the case of B. subtilis the protein is called UgtP and in the case of E. coli it is OpgH.

“It’s interesting,” Hill said, “that both organisms, which are more different from one another than we are from bakers’ yeast, are using the same system to coordinate changing size in response to nutrient availability.”

UgtP and OpgH are bifunctional proteins that are “moonlighting” as elements of the cell-division control systems. In both cases their day jobs are to help build the cell envelope. “We think they are communicating not only how much glucose there is in the cell, but also how fast the cell is growing,” Levin said. “The sensor says not only is food abundant, but we’re also growing really fast, so we should be bigger.”

Both proteins delay division by interfering with FtsZ, the first protein to move to the division site, where it assembles into a scaffold and recruits other proteins to form a constriction ring.

“Very little is known about the assembly of the ring,” Hill said. “There are a dozen essential division proteins and we don’t know what half of them do. Nor do we understand how the ring develops enough force to constrict.”

“We do know FtsZ exists in two states,” Hill added. “One is a small monomer and the other is many monomers linked together to form a multi-unit polymer. We think the polymers bind laterally to form a scaffold and then, with the help of other proteins, make a meshwork that goes around the cell.

UgtP and OpgH both interfere with the ability of FtsZ to form the longer polymers necessary for assembly of the constriction ring.

When nutrient levels are low, UgtP and OpgH are sequestered away from the division machinery. FtsZ is then free to assemble into the scaffold supporting the constriction ring so the cell can divide. Because division proceeds unimpeded, cells are smaller when they divide.

What about other bacteria?

This control system helps to explain the 60-year-old observation that bacterial cells get bigger when they are shifted to a nutrient-rich medium.

Comparing the mechanisms that govern cell division in E. coli and B. subtilis reveals conserved aspects of cell size control, including the use of UDP-glucose, a molecule common to all domains of life, as a proxy for nutrient availability, and the use of moonlighting proteins to couple growth-rate-dependent phenomena to the central metabolism.

But much more is known about these model organisms, which many labs study, than the average bacterium. Nobody is sure how many species of bacteria there are—somewhere between 10 million and a billion at a guess—and they don’t all divide the way B. subtilis and E. coli do.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Midlife Changes in Alzheimer’s Biomarkers May Predict Dementia
Studying brain scans and cerebrospinal fluid of healthy adults, scientists have shown that changes in key biomarkers of Alzheimer's disease during midlife may help identify those who will develop dementia years later, according to new research.
Tuesday, July 07, 2015
Unusual Comparison Nets New Sleep Loss Marker
Paul Shaw, PhD, a researcher at Washington University School of Medicine in St. Louis, uses what he learns in fruit flies to look for markers of sleep loss in humans.
Wednesday, May 08, 2013
Tiny Probes Shine Brightly to Reveal the Location of Targeted Tissues
Called BRIGHTs, the tiny probes described in the online issue of Advanced Materials, bind to biomarkers of disease and, when swept by an infrared laser, light up to reveal their location.
Friday, November 23, 2012
Amyloid Deposits in Cognitively Normal People may Predict Risk for Alzheimer's Disease
The studies linked higher amounts of the protein deposits in dementia-free people with greater risk for developing the disease.
Wednesday, December 16, 2009
Scientific News
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
First Artificial Ribosome Designed
Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
HIV Susceptibility Linked to Little-Understood Immune Cell Class
High levels of diversity among immune cells called natural killer cells may strongly predispose people to infection by HIV, and may be driven by prior viral exposures, according to a new study.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Study Finds Non-Genetic Cancer Mechanism
Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Rice Disease-Resistance Discovery Closes the Loop for Scientific Integrity
Researchers reveal how disease resistant rice detects and responds to bacterial infections.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!