These compounds, small organic molecules that they call 'conversation stoppers,' could help deliver a powerful one-two punch to knock out deadly infections when combined with the killing power of antibiotics, the scientists say. In addition, these 'conversation stoppers' do not target bacterial growth, so the potential for the development of bacterial resistance is minimized. This research, which is funded by the National Institutes of Health, could lead to new drugs to fight infections, was described today at the 232nd national meeting of the American Chemical Society.
"There is an urgent, global need for new antibacterial therapies," says study leader Helen Blackwell, Ph.D., an assistant professor of chemistry at the University. "The ability to interfere with bacterial virulence by intercepting bacterial communication networks represents a new therapeutic approach and is clinically timely."
Bacteria use chemical signals to initiate the majority of human infections. When these signals reach a certain threshold (in a process known as quorum sensing), pathogenic bacteria will change their mode of growth and produce virulence factors that lead to infection. These chemical signals also trigger the bacteria to produce slimy biofilms that cloak the bacteria and make the colony physically resistant to antibiotics.
Attempts to block bacterial quorum sensing are being conducted by a growing number of research groups. Many of these studies have focused on a group of small molecules called N-acylated L-homoserine lactones (AHLs), which are key signaling molecules used by Gram-negative bacteria.
But discovery of these molecules has been a relatively slow process until now. Blackwell and her associates have found that the use of 'microwave-assisted chemistry,' a novel laboratory technique for heating chemical reactions using microwaves, can dramatically accelerate the synthesis of AHL analogs that can either block or stimulate bacterial communication.
"Using microwave heating and combinatorial techniques to generate libraries of molecules, we can now produce and test in one day a group of compounds that previously would have taken a month to study using conventional techniques," Blackwell says.
So far, the researchers have identified at least two compounds that show particular promise at blocking biofilm formation in Pseudomonas aeruginosa, a bacterium that is a common cause of death in people with cystic fibrosis, AIDS and severe burns. In collaborative research with Fred Ausubel, Ph.D., a molecular biologist at Massachusetts General Hospital in Boston, Blackwell and her colleagues demonstrated that several of these compounds can extend the lives of worms infected with P. aeruginosa.
Recently, Blackwell designed 'conversation stoppers' that are specific to one bacterial strain and not others, allowing more efficient, selective attack on specific bacterial strains. This selectivity can help avoid disrupting beneficial bacteria, such as those in the gut that aid digestion, she says.
Some 'conversation stoppers' also hold promise for fighting crop diseases, biofilm formation on medical implants and catheters, and even bioterror agents. More studies are needed, says Blackwell, adding that her compounds haven't been tested in humans or plants but says that those tests are anticipated.
Michael Bernstein | EurekAlert!
Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)
Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
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...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
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,...
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...
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...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
13.12.2017 | Health and Medicine
13.12.2017 | Physics and Astronomy
13.12.2017 | Life Sciences