Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Solving the efficiency of Gram-negative bacteria

22.03.2019

Researchers have discovered how antibiotic-resistant bacteria construct their defense system, which could lead to new treatments for untreatable infections

Superbugs, also known as Gram-negative bacteria, are causing a global health crisis. Each year in the United States, at least two million people contract an antibiotic-resistant infection, according to the Centers for Disease Control (CDC). Of those, 23,000 people die.


MRSA, pictured here, has developed resistance to certain antibiotic treatments.

Credit: National Institutes of Health (NIH)

One way to stymie this crisis is to avoid contraction. But no one goes looking for bacterial infections. So, while health care professionals and food industries work to constrict the spread of E. coli, staph, and the deadly C. difficile infections, researchers are looking for new ways to skirt the impressive Gram-negative defense system.

Daniel Kahne, the Higgins Professor of Chemistry and Chemical Biology, and his lab are dedicated to determining how Gram-negative bacteria work. In the last decade, he and his team discovered an integral machine that builds each bacterium's powerful protection, an outer membrane constructed with a beefy molecule called lipopolysaccharide (LPS).

"Because there are no antibiotics for some Gram-negative infections, learning how the outer membrane is assembled and how to interfere with assembly has major medical implications," Kahne says.

Construction isn't simple. The bulky LPS is made inside the bacteria's cytoplasm, which is separated from the outer membrane by two additional barriers. Within the cytoplasm, the molecule ATP provides enough energy to produce the LPS building blocks and move them around the cell, like microscopic construction workers. But these workers (ATP) cannot cross the membrane barriers to transport LPS to the outer membrane work site.

Graduate student Tristan Owens decided to solve this mystery. In 2013, after spending a year teaching in Qatar, Owens returned to the United States to join the Kahne lab. That Fall, he told Kahne he planned to figure out how LPS gets to the outer membrane, a problem that scientists have been working on since the early 1970s. "As advisors often do, I assured him this would be possible," says Kahne.

To tackle the mystery, Owens would have to answer two major questions. First, if those tiny construction workers cannot follow LPS through the bacterial membranes, what pushes the molecule where it needs to go? He and the Kahne lab already discovered that a protein bridge guides the LPS across. But, without any energy to push the building blocks through, they should just fall back into the cytoplasm like so many apples thrown into the air.

For the second question, Owens would have to determine how LPS gets onto the protein bridge in the first place: How does the bacterial machinery distinguish LPS from the other molecules floating around in the cytoplasm?

"It was estimated in the 1970s that it would be necessary to move about three million LPS molecules every five minutes per cell to make the outer membrane," Kahne says. The bacterial machines had to be efficient. Now, six years and a dissertation later, Owens can explain how they run their well-organized operation.

In a paper published in Nature, first author Owens identifies two crystal structures responsible for extracting LPS from the cytoplasm and moving the molecule onto the protein bridge. Previous research proposed that LPS gets to the bridge via multiple pathways, but Owens' work determined that ATP shuttles the molecule along just one path.

Owens also discovered how the LPS continues to move through the bridge without help from the ATP construction workers. Like a Pez machine, the protein bridge opens and closes gates that keep the LPS moving up toward the outer membrane. "The gate provides an explanation for unidirectional transport," Kahne says, "because gate closure prevents backflow."

The more scientists know about how Gram-negative bacteria build their outer membrane, the closer they get to dismantling their powerful defenses. Now, with this decades-old mystery solved, researchers can start to develop new drugs that slow the bacteria's efficiency, hobble their machinery, and make them vulnerable to our antibiotics once again.

Media Contact

Caitlin McDermott-Murphy
cmcdermottmurphy@fas.harvard.edu
617-496-2618

 @HarvardResearch

http://www.harvard.edu 

Caitlin McDermott-Murphy | EurekAlert!
Further information:
https://chemistry.harvard.edu/news/solving-efficiency-gram-negative-bacteria
http://dx.doi.org/10.1038/s41586-019-1039-0

More articles from Life Sciences:

nachricht If Machines Could Smell ...
19.07.2019 | Fraunhofer-Institut für Produktionstechnik und Automatisierung IPA

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Heat flow through single molecules detected

19.07.2019 | Physics and Astronomy

Heat transport through single molecules

19.07.2019 | Physics and Astronomy

Welcome Committee for Comets

19.07.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>