Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover two-component lantibiotic with therapeutic potential

01.11.2006
The discovery and preparation of a naturally occurring antibiotic could open the door to new therapeutic drugs for treating nasty infections.

The rapid spread of drug-resistant bacterial strains poses a persistent threat to human health, and requires new sources of antibiotics to treat infections. Researchers at the University of Illinois at Urbana-Champaign are tackling this problem by discovering and preparing natural antibiotics called lantibiotics.

Lantibiotics are a class of very potent antimicrobial compounds whose antimicrobial properties are attributed to their structure. They possess unusual sulfur bridged rings that provide structural rigidity for binding their cellular targets. Lantibiotics are commonly used in the food industry to inhibit the growth of microorganisms.

"Having the ability to make analogs of these naturally occurring antibiotics gives us the flexibility to look for improvements in properties such as toxicity, biostability and bioavailability," said Wilfred van der Donk, a William H. and Janet Lycan Professor of Chemistry at the U. of I. He is a corresponding author of a paper that will be posted online this week ahead of regular publication by the Proceedings of the National Academy of Sciences. In previous work, van der Donk first identified the molecular activity of an enzyme (LctM) responsible for naturally turning a small protein into a lantibiotic. That discovery, reported in the journal Science in 2004, involved lacticin 481, a lantibiotic produced by several strains of Lactococcus lactis, a bacterium used in cheese production.

In March 2006, van der Donk's team reported, again in Science, the synthesis of the lantibiotic nisin. The most studied lantibiotic, nisin has been used as a food preservative for more than 40 years without the development of significant antibiotic resistance.

Then, in the Oct. 26 issue of Chemistry and Biology, the team demonstrated that LctM could accept substrates vastly different from its natural substrate, in vitro.

"Normally, enzymes are very selective, and will work only on their natural substrate," said van der Donk, who is also an affiliate of the university's Institute for Genomic Biology. "We showed that our enzyme could modify many synthetic substrates, and produce sulfur bridged rings of different sizes and shapes. This offered us the opportunity to control and alter the structure of lantibiotics."

In their latest work, to be published in PNAS, van der Donk and his collaborators describe a new two-component lantibiotic. These lantibiotic systems utilize two peptides that are each post-translationally modified to an active form, and act in synergy to provide antibacterial activity.

"Given the synergy observed among two-component lantibiotics, which display similar or higher activity than the best single-component lantibiotic, nisin, the possibility of engineering new lantibiotics with therapeutic potential is even greater for these systems," van der Donk said.

Using bioinformatics, the researchers found genes annotated in the fully sequenced genome of the Gram-positive bacterium Bacillus halodurans C-125 as precursors of the lantibiotics mersacidin and cytolysin. This strain had not previously been reported to produce a lantibiotic.

The new two-component lantibiotic was named haloduracin by its discoverers. "The bacterium that produces haloduracin grows at pH 9 and above, suggesting that the lantibiotic it produces will be stable in the human body, unlike nisin, which is unstable at pH 7 and above," van der Donk said. Significantly, the researchers succeeded in expressing in the bacterium Escherichia coli the machinery to produce haloduracin, thereby creating the first in vitro biosynthesis of a two-component lantibiotic.

"The in vitro biosynthesis opens the door to new, intriguing possibilities involving antimicrobial peptide design and engineering," van der Donk said. "Now we can start applying all the lessons we learned with lacticin 481."

James E. Kloeppel | EurekAlert!
Further information:
http://www.uiuc.edu

Further reports about: Donk antibiotic bacterium lantibiotic nisin therapeutic two-component

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>