Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Measures Holes Antibacterials Create in Cell Walls

11.01.2013
The rise of antibiotic-resistant bacteria has initiated a quest for alternatives to conventional antibiotics.

One potential alternative is PlyC, a potent enzyme that kills the bacteria that causes strep throat and streptococcal toxic shock syndrome. PlyC operates by locking onto the surface of a bacteria cell and chewing a hole in the cell wall large enough for the bacteria’s inner membrane to protrude from the cell, ultimately causing the cell to burst and die.

Research has shown that alternative antimicrobials such as PlyC can effectively kill bacteria. However, fundamental questions remain about how bacteria respond to the holes that these therapeutics make in their cell wall and what size holes bacteria can withstand before breaking apart. Answering those questions could improve the effectiveness of current antibacterial drugs and initiate the development of new ones.

Researchers at the Georgia Institute of Technology and the University of Maryland recently conducted a study to try to answer those questions. The researchers created a biophysical model of the response of a Gram-positive bacterium to the formation of a hole in its cell wall. Then they used experimental measurements to validate the theory, which predicted that a hole in the bacteria cell wall larger than 15 to 24 nanometers in diameter would cause the cell to lyse, or burst. These small holes are approximately one-hundredth the diameter of a typical bacterial cell.

“Our model correctly predicted that the membrane and cell contents of Gram-positive bacteria cells explode out of holes in cell walls that exceed a few dozen nanometers. This critical hole size, validated by experiments, is much larger than the holes Gram-positive bacteria use to transport molecules necessary for their survival, which have been estimated to be less than 7 nanometers in diameter,” said Joshua Weitz, an associate professor in the School of Biology at Georgia Tech. Weitz also holds an adjunct appointment in the School of Physics at Georgia Tech.

The study was published online on Jan. 9, 2013 in the Journal of the Royal Society Interface. The work was supported by the James S. McDonnell Foundation and the Burroughs Wellcome Fund.

Common Gram-positive bacteria that infect humans include Streptococcus, which causes strep throat; Staphylococcus, which causes impetigo; and Clostridium, which causes botulism and tetanus. Gram-negative bacteria include Escherichia, which causes urinary tract infections; Vibrio, which causes cholera; and Neisseria, which causes gonorrhea.

Gram-positive bacteria differ from Gram-negative bacteria in the structure of their cell walls. The cell wall constitutes the outer layer of Gram-positive bacteria, whereas the cell wall lies between the inner and outer membrane of Gram-negative bacteria and is therefore protected from direct exposure to the environment.

Georgia Tech biology graduate student Gabriel Mitchell, Georgia Tech physics professor Kurt Wiesenfeld and Weitz developed a biophysical theory of the response of a Gram-positive bacterium to the formation of a hole in its cell wall. The model detailed the effect of pressure, bending and stretching forces on the changing configuration of the cell membrane due to a hole. The force associated with bending and stretching pulls the membrane inward, while the pressure from the inside of the cell pushes the membrane outward through the hole.

“We found that bending forces act to keep the membrane together and push it back inside, but a sufficiently large hole enables the bending forces to be overpowered by the internal pressure forces and the membrane begins to escape out and the cell contents follow,” said Weitz.

The balance between the bending and pressure forces led to the model prediction that holes 15 to 24 nanometers in diameter or larger would cause a bacteria cell to burst. To test the theory, Daniel Nelson, an assistant professor at the University of Maryland, used transmission electron microscopy images to measure the size of holes created in lysed Streptococcus pyogenes bacteria cells following PlyC exposure.

Nelson found holes in the lysed bacteria cells that ranged in diameter from 22 to 180 nanometers, with a mean diameter of 68 nanometers. These experimental measurements agreed with the researchers’ theoretical prediction of critical hole sizes that cause bacterial cell death.

According to the researchers, their theoretical model is the first to consider the effects of cell wall thickness on lysis.

“Because lysis events occur most often at thinner points in the cell wall, cell wall thickness may play a role in suppressing lysis by serving as a buffer against the formation of large holes,” said Mitchell.

The combination of theory and experiments used in this study provided insights into the effect of defects on a cell’s viability and the mechanisms used by enzymes to disrupt homeostasis and cause bacteria cell death. To further understand the mechanisms behind enzyme-induced lysis, the researchers plan to measure membrane dynamics as a function of hole geometry in the future.

CITATION: Mitchell GJ, Wiesenfeld K, Nelson DC, Weitz JS, “Critical cell wall hole size for lysis in Gram-positive bacteria,” J R Soc Interface 20120892 (2013): http://dx.doi.org/10.1098/rsif.2012.0892.

Research News
Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia 30332-0181
Media Relations Contact: John Toon (404-894-6986)(jtoon@gatech.edu).
Writer: Abby Robinson

Abby Robinson | Newswise
Further information:
http://www.gatech.edu

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>