(Press-News.org) A study published in Immunity by physician-scientist Read Pukkila-Worley, MD, and MD/PhD students Nicholas D. Peterson and Samantha Y. Tse describes a new manner of detecting microbial infection that intercepts pathogen-derived signals of growth to assess the relative threat of virulent bacteria. A nuclear hormone receptor in the nematode C. elegans senses a toxic metabolite produced by the bacterial pathogen Pseudomonas aeruginosa to activate innate immunity. These data reveal an ancient strategy that informs the origins of pathogen detection and may be among the most primordial forms of immune sensing in animals.
“Our research adds to our understanding of how hosts differentiate between beneficial and harmful bacteria, which teaches us something important about how our immune systems evolved,” said Dr. Pukkila-Worley, associate professor of medicine.
Distinguishing potentially harmful pathogens from benign microorganisms is one of the primary functions of the innate immune system in all animals. This is particularly important for nematodes, such as C. elegans—the transparent microscopic worm often used as a model organism to study genetics and gene function—that consume bacteria as their food source.
Working with Pseudomonas aeruginosa, a bacteria that commonly infects immune-compromised patients in the hospital and is increasingly resistant to standard antibiotic treatments, Pukkila-Worley and colleagues performed a series of genetic screens with mutant bacteria, one-by-one, to see if any impacted the innate immune system response in C. elegans.
They found that bacteria that cannot produce a specific phenazine metabolite were able to avoid detection by the innate immune system, suggesting that the bacterial phenazine metabolite was sensed to activate innate immunity.
“This result was intriguing because P. aeruginosa use phenazines for growth and virulence. Thus, the innate immune system can intercept signals produced by bacteria in order to identify bacteria that have grown to dangerous levels and are poised to cause disease,” said Pukkila-Worley.
Researchers in the Pukkila-Worley lab designed a second experiment to identify the sensor in the host that detects these phenazine metabolites. They discovered that a specialized type of transcription factor, a nuclear hormone receptor, binds the phenazine metabolite and directly activates anti-pathogen defenses.
“One of the striking things about our results is that C. elegans senses this bacterial metabolite to detect an individual bacterial pathogen in a remarkably specific manner from among its bacterial food,”said Peterson, an MD/PhD student in the Pukkila-Worley lab.
In humans, pattern-recognition systems in the intestine involving Toll-like receptors scan the physical structure of different bacteria to sense the presence of infectious microorganisms. Nematodes lost pattern-recognition receptors in evolution. Pukkila-Worley and colleagues show that nematodes use nuclear hormone receptors to detect specific pathogen-derived metabolites to activate innate immunity, which represents a new type of pattern-recognition.
Since C. elegans have 274 nuclear hormone receptors, it’s possible that the nematode genome contains dozens of these metabolite recognition systems. Nuclear hormone receptors are also found in most animals, including humans, suggesting that similar metabolite detection systems might exist in other organisms.
“It’s remarkable that C. elegans evolved mechanisms to differentiate good and bad bacteria even without canonical receptors for pathogen detection. This further supports the importance of understanding how our immune system evolved over time to deepen our understanding of host-microbiome interactions,” said Tse, an MD/PhD student in the Pukkila-Worley lab.
END
UMass Chan investigators identify new pattern recognition system that monitors disease-causing bacteria in C. elegans
A nuclear hormone receptor intercepts pathogen-derived signals of growth and virulence, revealing an evolutionarily ancient strategy of immune sensing
2023-03-07
ELSE PRESS RELEASES FROM THIS DATE:
Blood test identifies acute myeloid leukemia patients at greater risk for relapse after bone marrow transplant
2023-03-07
Blood test identifies acute myeloid leukemia patients at greater risk for relapse after bone marrow transplant
A small portion of adults in remission from a deadly blood cancer had persisting mutations that were detected, which predicted their risk of death from having the cancer return
Researchers at the National Institutes of Health show the benefits of screening adult patients in remission from acute myeloid leukemia (AML) for residual disease before receiving a bone marrow transplant. The findings, published in JAMA, support ongoing research aimed ...
Whistleblowers losing faith in media impact
2023-03-07
The whistleblowers who once trusted journalism are losing faith in the institution.
A new study from the University of Georgia found that many whistleblowers who reached out to journalists in the past no longer believe media has the same ability to motivate change, and they feel let down by a system they once trusted.
“If you don’t believe that an outlet or journalist can carry you across the finish line—meaning can affect change, attract enough attention and attract the attention of the right people—then you’re losing faith,” said Karin Assmann, study lead and assistant professor in UGA’s Grady College of Journalism ...
STEP Demo pilot plant achieves supercritical CO2 fluid conditions
2023-03-07
SAN ANTONIO — March 7, 2023 —The Supercritical Transformational Electric Power (STEP) Demo pilot plant, a $155 million, 10-megawatt supercritical carbon dioxide (sCO2) test facility at Southwest Research Institute (SwRI) in San Antonio, developed in partnership with GTI Energy and GE Research and sponsored by the U.S. Department of Energy, has successfully achieved its first operation with CO2 at supercritical fluid conditions in its compressor section. This accomplishment represents significant progress toward ...
Splicing deregulation detected and targeted in type of childhood leukemia
2023-03-07
Pediatric acute myeloid leukemia or pAML is a childhood blood cancer, one that has proved confounding to clinicians and researchers, with a high relapse rate and relatively few identified genetic mutations (compared to the adult version) that might explain its cause.
In a new study, published in the March 7, 2023 issue of Cell Reports, an international team led by scientists and physicians at University of California San Diego School of Medicine deployed an array of analytical and gene-splicing tools to parse more deeply the mysteries of mutation in pAML.
“Compared to adult AML, pediatric AML is associated with relatively ...
Synchronizing to a beat predicts how well you get ‘in sync’ with others
2023-03-07
How well you synchronize to a simple beat predicts how well you synchronize with another mind, according to a new Dartmouth study published in Scientific Reports.
Previous work has demonstrated that the pupil dilation patterns of speakers and listeners synchronize spontaneously, illustrating shared attention. The team set out to understand how the tendency to synchronize in this way may vary at the individual level and generalize across contexts, as it has been widely debated whether one form of synchrony bears any relationship to another.
“We were ...
How high altitude changes your body’s metabolism
2023-03-07
SAN FRANCISCO, CA—March 7, 2023—Compared to those of us who live at sea level, the 2 million people worldwide who live above 4,500 meters (or 14,764 feet) of elevation—about the height of Mount Rainier, Mount Whitney, and many Colorado and Alaska peaks—have lower rates of metabolic diseases such as diabetes, coronary artery disease, hypercholesterolemia, and obesity.
Now, researchers at Gladstone Institutes have shed light on this phenomenon. They showed how chronically low oxygen levels, such as those experienced at high elevation, rewire how mice burn sugars ...
Endocrine Society elects Newell-Price as 2024-2025 President
2023-03-07
Endocrine Society members elected John Newell-Price, M.D., Ph.D., F.R.C.P., as its 2024-2025 President. He will serve as President-Elect for a year beginning in June 2023 before becoming President in June 2024.
Newell-Price is Professor of Endocrinology at the University of Sheffield in Sheffield, United Kingdom. He also is head of the endocrinology service at the Sheffield Teaching Hospitals NHS Foundation Trust and of the European Neuroendocrine Tumor Society at the hospital.
Newell-Price’s clinical expertise ...
Genetic and socioeconomic factors interact to affect risk of type 2 diabetes and obesity
2023-03-07
BOSTON – New research led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), indicates that socioeconomic and genetic factors likely interact in an additive way to affect people’s risks of developing obesity and type 2 diabetes. The findings, which are published in Diabetes Care, suggest that interventions to improve socioeconomic deprivation may decrease metabolic diseases at the individual and community levels, especially among people with concomitant high genetic risk.
Genetic and socioeconomic factors—one intrinsic and unmodifiable and ...
Heart tissue heads to space to aid research on aging and impact of long spaceflights
2023-03-07
Note: Johns Hopkins Medicine researchers Deok-Ho Kim and Devin Mair will participate in a NASA teleconference for journalists on Tuesday, March 14, at 11 a.m. ET.
Johns Hopkins Medicine researchers are collaborating with NASA to send human heart “tissue-on-a-chip” specimens into space as early as March. The project is designed to monitor the tissue for changes in heart muscle cells’ mitochondria (their power supply) and ability to contract in low-gravity conditions.
The tissue samples will ...
Heart toggles between maintenance and energy-boost mode using ribosomes
2023-03-07
Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have discovered a mechanism involving ribosomes which helps the heart toggle between a ‘regular maintenance mode’ for day-to-day function and an ‘energy-boost mode’ which aids recovery for high-demand situations including heart attacks. The findings are published in a ‘Breakthrough Article’ in the journal Nucleic Acids Research, a distinction awarded to studies that answer long-standing questions in the field.
Ribosomes are the molecular factories that manufacture proteins in all living cells. Historically, they have been ...
LAST 30 PRESS RELEASES:
Graz researchers discover what stiffens the aorta
Breakthrough in atomic-level etching of hafnium oxide, a promising material for advanced semiconductors
How evolution explains autism rates in humans
Swedish psychologist transforms mental health access through digital therapy revolution
Centenarian neuroscientist inspires blueprint for vibrant longevity through mentorship and connection
King’s College London researcher advances psychiatric genomics through pioneering polygenic scoring innovations
Study questions ocean origin of organics in Enceladus’s plumes
Look out for the keyhole: How to find the safest spots to deflect a hazardous asteroid
The older we get, the fewer favorite songs we have
Face‑/edge‑shared 3D perovskitoid single crystals with suppressed ion migration for stable X‑ray detector
Multiple solutions help fly embryos overcome the fundamental problem of ‘tissue tectonic collision’
GLP-1 weight-loss drugs pose hidden risks for young women
Strategies for enhancing energy‑level matching in perovskite solar cells: An energy flow perspective
3D‑printed boron‑nitrogen doped carbon electrodes for sustainable wastewater treatment via MPECVD
Screening anionic groups within zwitterionic additives for eliminating hydrogen evolution and dendrites in aqueous zinc ion batteries
New tectonic geodynamics textbook bridges scientific disciplines
Tiny and powerful – metamaterial lenses for your phones and drones
Study used AI models to improve prediction of chronic kidney disease progression to end stage renal disease
Peanut shell biochar composite shows promise for removing antibiotic-resistant bacteria from aquaculture wastewater
Compact genetic light switches transform disease control
Sunglasses for plants, and sustainable agriculture
Nearly half of those with diabetes unaware they have the disease
Emergency department visits by uninsured children in Texas soar 45% after COVID-era federal funding ends
Bright children from poorer backgrounds twice as likely to receive hospital mental health treatment than affluent high-achievers
‘Artificial cartilage’ could improve arthritis treatment
Breathing device could have profound impact on survival for people with sleep apnoea and type 2 diabetes
Artificial intelligence assessment indicates stress levels in farmed Amazonian fish
Keith Cole receives grant to conduct integrated research on mobility, cognition and aging
Internationally recognized malaria researcher Stefan Kappe, Ph.D., appointed new director of the UM School of Medicine's Center for Vaccine Development and Global Health
Lung cancer genetics study launches open-source data platform to research community
[Press-News.org] UMass Chan investigators identify new pattern recognition system that monitors disease-causing bacteria in C. elegansA nuclear hormone receptor intercepts pathogen-derived signals of growth and virulence, revealing an evolutionarily ancient strategy of immune sensing