No matter how many times it's demonstrated, it's still hard to envision bacteria as social, communicating creatures.
But by using a signaling system called "quorum sensing," these single-celled organisms radically alter their behavior to suit their population. In short, some bacteria "know" how many of them are present, and act accordingly.
Once the population of quorum-sensing bacteria reaches the millions, it may change from innocuous to pathogenic, or from unhelpful to helpful. The quorum-sensing messages are carried in small molecules that the bacteria release and whose concentration bacteria can measure.
Blocking such a signal can prevent a bacterium from turning, in common language, nasty.
Helen Blackwell, a professor of chemistry at the University of Wisconsin-Madison, has been making artificial compounds that mimic the natural quorum-sensing signals, including some that block a natural signal from binding to its protein target.
In research published today in the journal Chemistry & Biology, Blackwell changed key building blocks in these protein targets one by one. "If that part of the protein is important, the change will have a significant effect on our signal's activity," she explains.
In the study performed with recent graduate students Joseph Gerdt and Christine McInnis, Blackwell expected to knock out, or deactivate, the signals by making these point modifications. Sometimes, however, the changes actually converted an activation signal into a deactivation signal, or vice versa.
"It was surprising that making minor tweaks, very subtle changes, to the protein would convert a compound from an inhibitor to an activator, or turn an activator into an inhibitor," she says. "That shows that small-molecule control of quorum sensing is very finely tuned, much more than we even expected."
Quorum sensing is present in many, but not all, bacteria, and its advantage is clear. A few hundred bacteria cannot hope to overwhelm an animal host, so lying low and evading immune attack is a good survival tactic. But once they number in the millions, they can overwhelm the immune system and reproduce unscathed.
After quorum sensing delivers the attack signal, a group of bacteria can become more infective and start to secrete small, poisonous molecules or tissue-destroying enzymes. They may also form biofilms, a tough film that covers surfaces and protects bacteria members from harm.
Quorum sensing can also direct soil bacteria that infect soybean roots to harvest nitrogen from the atmosphere and improve crop yields.
Blackwell, who has studied quorum sensing for more than 10 years, explains that inhibiting quorum sensing may provide a new way to control pathogenic bacteria. "We are approaching the end of the antibiotic era, as bacteria evolve resistance to some of our most advanced drugs, and scientists are looking for alternative ways to control bacteria."
While current antibiotics are designed to kill microbes, the goal of quorum sensing would be to keep them "tame" and harmless, Blackwell says. "If these 'on/off' protein modifications are as important as we have found, they may help us design new compounds to inhibit quorum sensing and reduce the harm of bacterial infections, without causing the drug resistance that is producing so many problems today."
Reducing infectivity may allow the immune system to help clear the pathogen, Blackwell says. In procedures such as hip replacement or burn treatment, where infection is common, "this could be used prophylactically, or to augment and extend the lifetime of antibiotics."
The study was performed on Gram-negative bacteria, which are well protected from many drugs by a double membrane. "They also have lots of nasty pumps that eject those drugs that do enter," Blackwell says.
Gram negatives include E. coli, salmonella, shigella, and pseudomonas. Members of the group cause cholera, gonorrhea, meningitis, Legionnaire's disease, and respiratory and gastrointestinal diseases.
Gram negatives "are probably the most challenging infections, and the drugs that we have are really failing," Blackwell says. "But there is also a fascination in seeing how these very simple organisms team up to do things that are impossible in small numbers.
"The compounds and protein modifications we identified in the current study will serve as useful research tools to elucidate, and perhaps redirect, their 'tiny teamwork.'"
Helen Blackwell | Eurek Alert!
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Trade Fair News
22.03.2018 | Earth Sciences
22.03.2018 | Earth Sciences