Texas A&M team develops polymers that can kill bacteria

Dr. Quentin Michaudel and his research team have created a new family of polymers capable of killing bacteria without inducing antibiotic resistance — a major step in the fight against superbugs like E. coli and MRSA

Peer-Reviewed Publication

TEXAS A&M UNIVERSITY

Antibiotic-resistant bacteria have become a rapidly growing threat to public health. Each year, they account for more than 2.8 million infections, according to the U.S. Centers for Disease Control and Prevention. Without new antibiotics, even common injuries and infections harbor the potential to become lethal.

Scientists are now one step closer to eliminating that threat, thanks to a Texas A&M University-led collaboration that has developed a new family of polymers capable of killing bacteria without inducing antibiotic resistance by disrupting the membrane of these microorganisms.

“The new polymers we synthesized could help fight antibiotic resistance in the future by providing antibacterial molecules that operate through a mechanism against which bacteria do not seem to develop resistance,” said Dr. Quentin Michaudel, an assistant professor in the Department of Chemistry and lead investigator in the research, published Dec. 11 in the Proceedings of the National Academy of Sciences (PNAS).

Working at the interface of organic chemistry and polymer science, the Michaudel Laboratory was able to synthesize the new polymer by carefully designing a positively charged molecule that can be stitched many times to form a large molecule made of the same repeating charged motif using a carefully selected catalyst called AquaMet. According to Michaudel, that catalyst proves key, given that it has to tolerate a high concentration of charges and also be water-soluble — a feature he describes as uncommon for this type of process.

After achieving success, the Michaudel Lab put its polymers to the test against two main types of antibiotic-resistant bacteria — E. coli and Staphylococcus aureus (MRSA) — in collaboration with Dr. Jessica Schiffman’s group at the University of Massachusetts Amherst. While awaiting those results, the researchers also tested their polymers’ toxicity against human red blood cells.

“A common issue with antibacterial polymers is a lack of selectivity between bacteria and human cells when targeting the cellular membrane,” Michaudel explained. “The key is to strike a right balance between effectively inhibiting bacteria growth and killing several types of cells indiscriminately.”

Michaudel credits the multidisciplinary nature of scientific innovation and the generosity of dedicated researchers across the Texas A&M campus and country as factors in his team’s success in determining the perfect catalyst for their molecule assembly.

“This project was several years in the making and would not have been possible without the help of several groups, in addition to our UMass collaborators,” Michaudel said. “For instance, we had to ship some samples to the Letteri Lab at the University of Virginia to determine the length of our polymers, which required the use of an instrument that few labs in the country have. We are also tremendously grateful to [biochemistry Ph.D. candidate] Nathan Williams and Dr. Jean-Philippe Pellois here at Texas A&M, who provided their expertise in our assessment of toxicity against red blood cells.”

Michaudel says the team will now focus on improving the activity of its polymers against bacteria — specifically, their selectivity for bacterial cells versus human cells — before moving on to in vivo assays.

“We are in the process of synthesizing a variety of analogs with that exciting goal in mind,” he said.

The team’s paper, which features Michaudel Lab member and Texas A&M chemistry Ph.D. graduate Dr. Sarah Hancock ’23 as first author, can be viewed online along with related figures and captions. Other key contributors from the Michaudel Lab are chemistry graduate student An Tran ’23, postdoctoral scholar Dr. Arunava Maity and former postdoctoral scholar Dr. Nattawut Yuntawattana, who is now an assistant professor of materials science at Kasetsart University in Thailand.

This research was funded primarily by Michaudel’s National Institutes of Health Maximizing Investigators’ Research Award (MIRA) through the National Institute of General Medical Sciences.

A native of La Rochelle, France, Michaudel joined the Texas A&M Chemistry faculty in 2018 and holds a joint appointment in the Department of Materials Science and Engineering. In addition to an NIH MIRA in 2020, his career honors to date include a 2022 National Science Foundation Faculty Early Career Development (CAREER) Award, a 2022 American Chemical Society Polymeric Materials: Science and Engineering (PMSE) Young Investigator Award and a 2021 Thieme Chemistry Journals Award.

Learn more about Michaudel and his research at michaudellab.org.

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2311396120 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Ring-opening metathesis polymerization of N-methylpyridinium-fused norbornenes to access antibacterial main-chain cationic polymers

 

How jellyfish regenerate functional tentacles in days

Peer-Reviewed Publication

UNIVERSITY OF TOKYO

 

IMAGE: 

THE JELLYFISH CLADONEMA PACIFICUM EXHIBITS BRANCHED TENTACLES THAT CAN ROBUSTLY REGENERATE AFTER AMPUTATION.

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CREDIT: SOSUKE FUJITA, THE UNIVERSITY OF TOKYO

At about the size of a pinkie nail, the jellyfish species Cladonema can regenerate an amputated tentacle in two to three days — but how? Regenerating functional tissue across species, including salamanders and insects, relies on the ability to form a blastema, a clump of undifferentiated cells that can repair damage and grow into the missing appendage. Jellyfish, along with other cnidarians such as corals and sea anemones, exhibit high regeneration abilities, but how they form the critical blastema has remained a mystery until now.

A research team based in Japan has revealed that stem-like proliferative cells — which are actively growing and dividing but not yet differentiating into specific cell types — appear at the site of injury and help form the blastema.

The findings were published in the scientific journal PLOS Biology.

“Importantly, these stem-like proliferative cells in blastema are different from the resident stem cells localized in the tentacle,” said corresponding author Yuichiro Nakajima, lecturer in the Graduate School of Pharmaceutical Sciences at the University of Tokyo. “Repair-specific proliferative cells mainly contribute to the epithelium — the thin outer layer — of the newly formed tentacle.”

The resident stem cells that exist in and near the tentacle are responsible for generating all cellular lineages during homeostasis and regeneration, meaning they maintain and repair whatever cells are needed during the jellyfish’s lifetime, according to Nakajima. Repair-specific proliferative cells only appear at the time of injury.

“Together, resident stem cells and repair-specific proliferative cells allow rapid regeneration of the functional tentacle within a few days,” Nakajima said, noting that jellyfish use their tentacles to hunt and feed.

This finding informs how researchers understand how blastema formation differs among different animal groups, according to first author Sosuke Fujita, a postdoctoral researcher in the same lab as Nakajima in the Graduate School of Pharmaceutical Sciences.

“In this study, our aim was to address the mechanism of blastema formation, using the tentacle of cnidarian jellyfish Cladonema as a regenerative model in non-bilaterians, or animals that do not form bilaterally — or left-right — during embryonic development,” Fujita said, explaining that the work may provide insight from an evolutionary perspective.

Salamanders, for example, are bilaterian animals capable of regenerating limbs. Their limbs contain stem cells restricted to specific cell-type needs, a process that appears to operate similarly to the repair-specific proliferative cells observed in the jellyfish.

“Given that repair-specific proliferative cells are analogues to the restricted stem cells in bilaterian salamander limbs, we can surmise that blastema formation by repair-specific proliferative cells is a common feature independently acquired for complex organ and appendage regeneration during animal evolution,” Fujita said.

The cellular origins of the repair-specific proliferative cells observed in the blastema remain unclear, though, and the researchers say the currently available tools to investigate the origins are too limited to elucidate the source of those cells or to identify other, different stem-like cells.

“It would be essential to introduce genetic tools that allow the tracing of specific cell lineages and the manipulation in Cladonema,” Nakajima said. “Ultimately, understanding blastema formation mechanisms in regenerative animals, including jellyfish, may help us identify cellular and molecular components that improve our own regenerative abilities.”

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Funding:

The research is supported by grants from the Japan Society for the Promotion of Science KAKENHI, Japan Science and Technology Agency, Japan Agency for Medical Research and Development, and Japan’s National Institute for Basic Biology collaborative research program.

 

Related links:

Graduate School of Pharmaceutical Sciences: https://www.f.u-tokyo.ac.jp/en/

 

Research contacts:

Sosuke Fujita, Postdoctoral researcher

Graduate School of Pharmaceutical Sciences, The University of Tokyo

Email: sosuke.rinama@gmail.com

 

Yuichiro Nakajima, Lecturer

Graduate School of Pharmaceutical Sciences, The University of Tokyo

Email: nakaji97@g.ecc.u-tokyo.ac.jp

 

About the University of Tokyo

The University of Tokyo is Japan's leading university and one of the world's top research universities. The vast research output of some 6,000 researchers is published in the world's top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 4,000 international students. Find out more at www.u-tokyo.ac.jp/en/ or follow us on Twitter at @UTokyo_News_en

Resident stem cells (green) and repair-specific proliferative cells (red) contribute to tentacle regeneration in Cladonema.

CREDIT

Sosuke Fujita, The University of Tokyo

Regeneration of the jellyfish tentacle 

At 72 hours after amputation, the regenerating tentacle of Cladonema is fully functional.

CREDIT

Sosuke Fujita, The University of Tokyo

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JOURNAL

PLoS Biology

DOI

10.1371/journal.pbio.3002435 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Distinct stem-like cell populations facilitate functional regeneration of the Cladonema medusa tentacle

ARTICLE PUBLICATION DATE

21-Dec-2023

 

Evolution of tuberculosis – in new light

The evolution of TB, the earliest confirmed presence of the causative agents in human remains

Peer-Reviewed Publication

EÖTVÖS LORÁND UNIVERSITY

 

IMAGE: 

SMALL ROUND PITS AS LYTIC LESIONS INDICATE THE PRESENCE OF THE PATHOGEN IN THE CANCELLOUS BONE TISSUE THE VERTEBRAL BODIES, WHICH LEADS TO THE FOCAL DESTRUCTION OF BONE.  

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CREDIT: PHOTO BY KRISZTIÁN KISS (ELTE)

Recent research suggests that the emergence of tuberculosis infection in human populations dates back tens of thousands of years earlier than previously known cases in the Middle East. In collaboration with an international research team, Hungarian researchers have edited and published a special issue of the journal Tuberculosis.

In July 2022, the Department of Anthropology of the University of Szeged organised a conference on the paleopathology and evolution of tuberculosis. The ICEPT3 conference was closely linked to the NRDI-best funded research project of György Pálfi (Department of Anthropology, Szeged University), and the presentations of researchers from all over the world provided a comprehensive overview of the history of the pathogen, going beyond the previous knowledge.

In the last decades, the historical Carpathian Basin has become the best-researched region in the world in terms of TB infection, primarily as a result of the work of researchers from the Department of Biological Anthropology at the Faculty of Science and Informatics at University of Szeged the Department of Biological Anthropology at the Faculty of Science at Eötvös Loránd University and the Department of Anthropology at the Hungarian Natural History Museum. Recent analyses by György Pálfi, Ildikó Pap, and their colleagues suggest Neanderthal specimens from Subalyuk cave (Hungary), who lived more than 32,000 years ago, may have also suffered from TB infection. These new scientific discoveries place the appearance of tuberculosis in human populations tens of thousands of years earlier than the earliest known cases.

The first section of this Tuberculosis Supplement issue is dedicated to the memory of Professor David Ernest Minnikin, an outstanding scholar of TB evolution and a well-known pioneer in the field of mycobacterial research, who died in 2021. In the first articles, the authors commemorate his outstanding work and the remarkable findings which have enriched both the modern and ancient mycobacterial research community. The following papers are about essential ancient TB research results with active contributions by Professor Minnikin and collaborators: the above-mentioned discovery and analysis of paleopathological and paleomicrobiological traces of TB infection in the Subalyuk Neanderthal remains (Hungary). These results are of great importance for our knowledge of the evolution of tuberculosis, and these studies are closely related to the subjects of the articles that follow.

Two studies led by doctoral students from the Department of Biological Anthropology at ELTE have contributed significantly to the detailed exploration of the evolution of tuberculosis, reviewing previously known and publishing newly identified cases from inside the borders of today’s Hungary.

Anett Gémes and colleagues presented a detailed review of 18 cases alongside the introduction of 7 new cases. Three of the seven cases are from the Bronze Age (2600/2500-800 BC) when cases of skeletal tuberculosis from the Carpathian Basin had not been reported.

Krisztián Kiss and colleagues have reviewed 114 previously published cases of TB with the publication of the detailed description of an additional 39 new cases.

Thus, a comprehensive database representing the Carpathian Base of 2nd-16th centuries was established. Primary data (sex and age) and detailed description of pathological alterations are available for the affected individuals, illustrated by photo- and radiographs. It would not have been possible to collect this large number of cases without close cooperation between the Departments of Biological Anthropology of ELTE and SZTE, and between several other institutions, anthropologists, and archaeologists.

All articles in the volume will be available free of charge until 14 January 2024 at the following link (5 studies are Open Access and will remain available for download):  https://www.sciencedirect.com/journal/tuberculosis/vol/143/suppl/S

As the database includes detailed paleopathological descriptions furthermore photo- and radiographic documentations for skeletal tuberculosis, a deeper understanding of the natural course, macromorphological and radiological manifestation of the disease can be achieved. Thus, besides revealing temporal and spatial trends based on the results, the study can be also considered significant contribution to the paleopathological and clinical disciplines.

The conference and the accompanying special issue of Tuberculosis Journal highlight how a broad national collaboration in a given field, supported by an international network of researchers, can achieve tremendous and internationally outstanding results.

The number of cases representing this relatively small geographical region is unique around the globe, which is the result of the hard work of Hungarian anthropologists in the last decades. The many identified TB cases with the detailed descriptions provide a good basis for designing future molecular studies and test multiple hypotheses better to understand the evolutionary history of tuberculosis pathogen strains.

The entire proceedings of the conference were published in December 2023 in the prestigious journal Tuberculosis. An outstanding Hungarian-French-Italian collaboration among the University of Szeged, the Ecole Pratique des Hautes Etudes, the Eötvös Loránd University, the Université Paris-Saclay, and the Eurac Research has resulted in the publication of the latest international TB evolution research results.

The volume was edited in an international collaboration, thanks to the guest editorship of György Pálfi from Szeged University (Szeged, Hungary), Olivier Dutour from Ecole Pratique des Hautes Etudes - PSL University Paris and CNRS, Université Bordeaux Montaigne (France), Tamás Hajdu from ELTE (Budapest, Hungary), Christophe Sola from Université Paris-Saclay, Université Paris-Cité (France) and Albert Zink from Institute for Mummy Studies, EURAC Research (Bolzano, Italy). Of the 22 studies included, 10 are partly or entirely the work of Hungarian researchers.

All articles in the book are available free of charge until 14 January 2024 at the link below; five of the papers are open access and will remain open for download. Tuberculosis | Supplement Issue: Paleopathology and Evolution of Tuberculosis – Conference Proceedings from the 3rd International Congress on the Evolution and Paleoepidemiology of Tuberculosis (ICEPT-3, 5th–6th July 2022, Institute of Biology, University of Szeged, Szeged, Hungary) | ScienceDirect.com by Elsevier).

Pott’s disease in the spine is a pathognomic sign of Mycobacterium. The presence of the pathogen causes the destruction and collapse of the vertebral bodies resulting in gibbus formation and fusion (ankylosis) of the vertebrae. 

CREDIT

Photo by Évinger Sándor (Hungarian Natural History Museum)

The pathogens that cause TB can also affect the joints. The elbow joint in the picture is completely deformed due to the inflammation caused by pyogenic bacterial (possibly Mycobacterial) infection. 

CREDIT

Photo by Krisztián Kiss (ELTE).

JOURNAL

Tuberculosis

DOI

10.1016/j.tube.2023.102396 

ARTICLE TITLE

Tuberculosis in prehistory in Eastern Central Europe (Hungary) – Chronological and geographical distribution

 

Robots versus humans: Which would children trust more when learning new information?

Peer-Reviewed Publication

SINGAPORE UNIVERSITY OF TECHNOLOGY AND DESIGN

 

IMAGE: 

A CHILD WATCHING A ROBOT PROVIDE ACCURATE OR INACCURATE INFORMATION.

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CREDIT: SUTD

In this digital age, children are exposed to overwhelming amounts of information online, some of it unverified and increasingly generated by non-human sources, such as AI-driven language models. As children grow older, the ability to assess a source’s reliability is an important skill in cultivating critical thinking.

Children aged three to five years display selective trust based on the informant’s past accuracy when faced with both humans and robots, according to a study published in the journal Child Development titled, ‘Younger, not older, children trust an inaccurate human informant more than an inaccurate robot informant.’

“Children do not just trust anyone to teach them labels, they trust those who were reliable in the past. We believe that this selectivity in social learning reflects young children’s emerging understanding of what makes a good (reliable) source of information,” explained Li Xiaoqian, a research scholar at Singapore University of Technology and Design (SUTD) who co-authored the study with her PhD supervisor Professor Yow Wei Quin, a psychology professor and head of Humanities Arts and Social Sciences cluster at SUTD. “The question at stake is how young children use their intelligence to decide when to learn and whom to trust.”

In the study, participants from Singapore preschools such as ChildFirst, Red SchoolHouse and Safari House, aged between three and five, were split below and above the median age of 4.58 years old into ‘younger’ and ‘older’ cohorts respectively. They were paired with a robot or human informant, which either provided accurate or inaccurate labels to objects, such as ‘ball’ or ‘book’. The researchers then tested to see if the informant’s identity (human or robot) and track record as a reliable informant as well as the child’s age influenced the child’s trust in the informant to label things correctly in the future. 

Participants were presented with only one informant during the study, and their trust was measured by their willingness to accept new information. The humanoid social robot by SoftBank Robotics, NAO, which has a human-like but robotic voice, was used as the robot informant. To keep conditions comparable, the human informant matched her movements to those of the robot. An experimenter was also seated next to the participant to ask the necessary questions, so that the participant would not feel pressured to agree with the informant.

The study revealed that children were willing to accept new information from both human and robot informants who had previously given accurate information, but not from a potentially unreliable informant who had made mistakes in the past—especially when the informant was a robot. As for the age effect, the authors reported that younger children were likelier to accept information from an unreliable human than an unreliable robot, but older children were found to distrust or reject information from an unreliable informant, human or robot.

“These results implicate that younger and older children may have different selective trust strategies, especially the way they use informants’ reliability and identity cues when deciding who to trust. Together with other research on children’s selective trust, we show that as children get older, they may increasingly rely on reliability cues to guide their trust behaviour,” said Dr Li.

Previous research has shown that children rely on factors such as age, familiarity, and language to figure out whether an informant is reliable or not. It may be that younger children rely on identity cues like these more than they do epistemic evidence. As they get older, children place more emphasis on “what you know” than “who you are” when deciding to trust an informant.

This is the first study to ask the questions: (1) Do children draw different inferences about robots with varying track records of accuracy? and (2) Are these inferences comparable to those about humans?

“Addressing these questions will provide a unique perspective on the development of trust and social learning among children who are growing up alongside various sources of information, including social robots,” described Prof Yow.

This research has significant implications for pedagogy, where robots and non-human educational tools are increasingly integrated into the classroom. Children today may not perceive robots as trustworthy as humans if they have not interacted much with robots. However, as children gain more exposure to smart machines, they could be inclined to see robots as intelligent and reliable sources of knowledge.

Future studies could explore the selective learning development theory beyond the scope of word learning, such as tool usage, emotional expression congruency, or episodic domains such as location learning. For now, the researchers hope that their findings are considered in the realm of design pedagogy.

“Designers should consider the impact of perceived competence when building robots and other AI-driven educational tools for young children. Recognising the developmental changes in children’s trust of humans versus robots can guide the creation of more effective learning environments, ensuring that the use of technologies aligns with children’s developing cognitive and social needs,” emphasised Prof Yow.

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JOURNAL

Child Development

DOI

10.1111/cdev.14048 

 

UTHealth Houston researchers find link between lonely veterans and firearm purchases

Peer-Reviewed Publication

UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON

 

IMAGE: 

ALEXANDER TESTA, PHD, (LEFT) AND JACK TSAI, PHD, (RIGHT) FROM THE DEPARTMENT OF MANAGEMENT, POLICY AND COMMUNITY HEALTH WITH UTHEALTH HOUSTON SCHOOL OF PUBLIC HEALTH. (PHOTOS BY UTHEALTH HOUSTON)

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CREDIT: UTHEALTH HOUSTON

Low-income U.S. veterans who are experiencing feelings of loneliness are more likely to purchase firearms, according to new research from UTHealth Houston.

A study led by principal investigator Alexander Testa, PhD, assistant professor, and co-investigator Jack Tsai, PhD, professor, from the Department of Management, Policy and Community Health with UTHealth Houston School of Public Health, was published recently in Social Science & Medicine. 

“Loneliness was significantly associated with a higher likelihood of purchasing a firearm in the past year,” Testa said. “To put the findings in context, loneliness was measured on a scale of zero to six, and the findings showed that 13.7% of persons with a loneliness score of six had purchased a new firearm in the past year, compared to 5.1% of persons with a loneliness score of zero.”

Researchers collected data from a national survey conducted in December 2022 and January 2023 involving 1,004 low-income U.S. veterans. Utilizing Firth logistic regression, a method designed to address biases in small-sample studies, the study aimed to explore the association between loneliness and firearm acquisition in the past year.

Among the key findings, approximately 5.4% of all respondents reported purchasing a new firearm within the past year. The study revealed a positive association between loneliness and recent firearm acquisition, even after controlling for demographic, socioeconomic, and household variables.

“There are public health concerns about social isolation and safe firearm ownership as separate issues among veterans, and this study highlights a potential important connection between the two,” said Tsai, who is also regional dean in San Antonio. “Helping address one issue may affect the other, and it’ll be worthwhile to examine this further and determine whether this connection also exists among other adults.”

Investigators also discovered the potential risks associated with both loneliness and firearm ownership, including veteran suicide. The researchers said the findings show the necessity of targeted interventions to address loneliness and promote safe firearm practices within the veteran community, and may contribute valuable insights for future efforts to improve the mental health and well-being of U.S. military veterans.

Low-income U.S. veterans who are experiencing feelings of loneliness are more likely to purchase firearms, according to new research from UTHealth Houston.

A study led by principal investigator Alexander Testa, PhD, assistant professor, and co-investigator Jack Tsai, PhD, professor, from the Department of Management, Policy and Community Health with UTHealth Houston School of Public Health, was published recently in Social Science & Medicine. 

“Loneliness was significantly associated with a higher likelihood of purchasing a firearm in the past year,” Testa said. “To put the findings in context, loneliness was measured on a scale of zero to six, and the findings showed that 13.7% of persons with a loneliness score of six had purchased a new firearm in the past year, compared to 5.1% of persons with a loneliness score of zero.”

Researchers collected data from a national survey conducted in December 2022 and January 2023 involving 1,004 low-income U.S. veterans. Utilizing Firth logistic regression, a method designed to address biases in small-sample studies, the study aimed to explore the association between loneliness and firearm acquisition in the past year.

Among the key findings, approximately 5.4% of all respondents reported purchasing a new firearm within the past year. The study revealed a positive association between loneliness and recent firearm acquisition, even after controlling for demographic, socioeconomic, and household variables.

“There are public health concerns about social isolation and safe firearm ownership as separate issues among veterans, and this study highlights a potential important connection between the two,” said Tsai, who is also regional dean in San Antonio. “Helping address one issue may affect the other, and it’ll be worthwhile to examine this further and determine whether this connection also exists among other adults.”

Investigators also discovered the potential risks associated with both loneliness and firearm ownership, including veteran suicide. The researchers said the findings show the necessity of targeted interventions to address loneliness and promote safe firearm practices within the veteran community, and may contribute valuable insights for future efforts to improve the mental health and well-being of U.S. military veterans.

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JOURNAL

Social Science & Medicine

Disparities in preoperative goals of care documentation in veterans

JAMA Network Open

Peer-Reviewed Publication

JAMA NETWORK

About The Study: In this study of 13,000 patients, few patients undergoing surgical procedures completed preoperative life-sustaining treatment documentation, with disparities in documentation rates based on race, ethnicity, rurality of patient residence, history of mental health disability, and access to high-volume facilities within a Veterans Affairs cohort.

Authors: Adela Wu, M.D., of the U.S. Department of Veterans Affairs, in Palo Alto, California is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi: 10.1001/jamanetworkopen.2023.48235)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2023.48235?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=121923

About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

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JOURNAL

JAMA Network Open

 

Stinky, bitter, and painful: A novel insect repellent attacks multiple sensory pathways

Researchers from the National Institute for Physiological Sciences/the Exploratory Research Center on Life and Living Systems (ExCELLS) in Japan identified a TRPA1 stimulant acts as a novel insect repellent via bitter taste, nociceptive, and olfactory senses.

Peer-Reviewed Publication

NATIONAL INSTITUTES OF NATURAL SCIENCES

 

IMAGE: 

SENSORY PATHWAYS IN DROSOPHILA TO DETECT AND AVOID 2MT ARE SHOWN. FLIES ESCAPE FROM 2MT THROUGH OLFACTORY, TASTE, AND NOCICEPTIVE SENSORY PATHWAYS. THIS STUDY IDENTIFIED THAT TRPA1 EXPRESSED IN TASTE AND NOCICEPTIVE SENSORY NEURONS PLAY A MAJOR ROLE IN 2MT-INDUCED AVERSIVE BEHAVIORS. EVAPORATED 2MT IS ALSO DETECTED BY ORS IN OLFACTORY PATHWAY.

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CREDIT: SHOMA SATO

Okazaki, Japan – crop damage in agriculture and the transmission of vector-borne diseases by insect pests have become worldwide threat nowadays. Chemical treatments such as insecticides and repellents have been a major strategy against insect pests for centuries. Due to limited understanding of mechanisms of insect avoidance behavior, however, development of insect repellents has been delayed. To discover compounds that effectively repel insect pests, it is important to focus on key molecules associated with sensory, particularly aversive, responses. In this study, researchers identified a compound that induces robust aversive responses through multiple sensory pathways in the fruit fly, Drosophila melanogaster.

Among sensory receptors, Transient Receptor Potential (TRP) cation channels play a key role in nocifensive behaviors to various stimuli in many insect species. Particularly, TRPA1 channel has been extensively studied as it is activated by various hazardous chemicals. Therefore, insect TRPA1 stimulants are promising leads for novel repellents with a broad spectrum. Takaaki Sokabe and his colleagues at the National Institute for Physiological Sciences/the Exploratory Research Center on Life and Living Systems (ExCELLS) found that 2-methylthiazoline (2MT), an analog of a volatile compound found in fox urine, repels flies effectively, and revealed the molecular and cellular mechanisms of 2MT-induced aversions in the fly. They recently published their findings in Frontiers in Molecular Neuroscience.

"2MT is reported to evoke innate fear responses in mice via TRPA1, therefore we expected that the chemical possibly have an aversive effect on insects,” Sokabe says. “And it worked terrifically more than our expectation.”

Fly’s avoidance behaviors revealed that 2MT stimulates multiple sensory modalities: 2MT vapor acts on odorant receptors (ORs) in an olfactory pathway, and direct contact to 2MT activates TRPA1 in taste and nociceptive pathways. This resulted in apparent escaping from chemical source of male flies and avoidance of egg laying of female flies. Furthermore, The researchers demonstrated that TRPA1 is activated by 2MT through the direct interaction of 2MT to specific two amino acids in TRPA1.

“The action of 2MT on multiple sensory pathways seems to be a key for its high effectiveness,” says Takaaki Sokabe. “Because the amino acids essential for TRPA1 activation are highly conserved across a wide range of insect species, including agricultural pests and disease vectors, it will be important to test 2MT on many other insect pests to evaluate the spectrum.”

This new work could promote the development of novel insect repellents by focusing on TRP channels and other types of receptors as promising targets.

 

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JOURNAL

Frontiers in Molecular Neuroscience

DOI

10.3389/fnmol.2023.1249715 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Avoidance of thiazoline compound depends on multiple sensory pathways mediated by TrpA1 and ORs in Drosophila