Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A 'warhead' molecule to hunt down deadly bacteria

12.03.2015

Modifying bacterial lipids can label and target deadly bacteria, spare healthy cells

Targeting deadly, drug-resistant bacteria poses a serious challenge to researchers looking for antibiotics that can kill pathogens without causing collateral damage in human cells. A team of Boston College chemists details a new approach using a "warhead" molecule to attack bacteria -- and spare healthy human cells -- by targeting a pair of lipids found on the surface of deadly germs, according to a report today in the journal Nature Communications.

The new strategy required the researchers to develop a novel type of "warhead molecule" capable of selectively targeting bacteria, overcoming biological conditions that interfere with bonding to pathogens and avoiding healthy human cells, said Boston College Associate Professor of Chemistry Jianmin Gao, the lead author of the report.

The BC team found answers to those challenges in the covalent chemistry of lipids, Gao said.

"In contrast to other efforts focused on the charge-to-charge attraction between molecules, we are using a completely different mechanism to target bacterial cells," said Gao. "Our method exploits the covalent chemistry of lipids - where the lipids react with synthetic molecules to form new chemical structures based on the formation of new covalent bonds."

Pathogenic bacteria that are resistant to conventional antibiotics pose increasingly serious threats to public health. Researchers in medicinal chemistry, particularly those who seek to develop new antibiotics, are constantly looking for new ways to identify and differentiate bacterial pathogens from host cells within the human body.

Gao said bacterial cells are known to display a different set of lipids in their membranes. Prior research has focused on the use of positively charged peptides to target negatively charged lipids on the surface of bacterial cells. The approach has seen limited success as the charge-charge attraction between the attacking molecules and bacteria is prone to weakening by the presence of salt and other molecules, said Gao.

The researchers developed a novel, unnatural amino acid that serves as a suitable molecular warhead to target bacterial pathogens. Gao and his group sent the warhead molecule after bacterial lipids known as amine-presenting lipids -- specifically phosphatidylethanolamine (PE) and lysyl phosphatidylglycerol (Lys-PG) - which can be selectively derivatized to form iminoboronates, a covalent bond forming process that allows the selective recognition and labeling of bacterial cells.

In addition, because amine-presenting lipids are scarce on the surface of mammalian cells, they are able to seek out and label bacterial cells with a high degree of selectivity, Gao said. Furthermore, iminoboronate formation can be reversed under physiologic conditions, giving the new method a high degree of control and allowing the warhead molecules to self-correct if unintended targets are reached.

Gao said a large number of bacterial species present PE and Lys-PG on their surfaces, making the covalent labeling strategy applicable to many applications in the diagnosis of bacterial infections and the delivery of antibiotic therapies.

"For the short term, we hope this work will inspire other people to consider using covalent chemistry for interrogating biological systems," Gao said. "Going into the future, we are excited to explore the potential of our chemistry for imaging bacterial infections. We are also working hard to apply our current findings to facilitate the targeted delivery of potent antibiotics to bacterial cells only."

Media Contact

Ed Hayward
ed.hayward@bc.edu
617-552-4826

 @BostonCollege

http://www.bc.edu 

Ed Hayward | EurekAlert!

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton 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: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>