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Bacteria

A New Chapter in Vaccine Development: Combining Vaccination with Harmless Microorganisms to Combat Intestinal Bacteria

In the fight against bacterial pathogens, researchers are combining vaccination with targeted colonization of the intestine by harmless microorganisms. This approach could potentially mark a turning point in the antibiotics crisis.

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The fight against bacterial pathogens has taken an exciting turn with researchers combining vaccination with targeted colonization of the intestine by harmless microorganisms. This innovative approach could potentially mark a turning point in the antibiotics crisis, where antibiotic-resistant germs are becoming an increasing health problem.

The issue of intestinal bacteria is complex, as we rely on microorganisms to digest our food, but also face numerous pathogens that can cause diarrhea or life-threatening inflammation of organs. Scientists have been investigating vaccines against pathogenic microbes in the intestine, particularly those that antibiotics have become ineffective against due to resistance. However, deciphering the intestinal immune system has proven challenging.

Emma Slack, a professor at ETH Zurich and the University of Oxford’s Sir William Dunn School of Pathology, has made significant contributions to this area. Along with Médéric Diard, a professor at the Biozentrum of the University of Basel, and an international team of researchers, she has demonstrated how highly effective oral vaccinations can be formulated against intestinal pathogens by combining them with harmless bacteria that compete with pathogenic microbes for food and starve them out.

The researchers used a study on mice to demonstrate this approach, where vaccination or harmless bacteria alone had a significantly smaller impact compared to the combined approach. The competitor strains were chosen or produced to live in the same section of intestine as the pathogens, coping with similar acidity and oxygen levels, and using the same nutrients.

“This is like gardening,” explains Slack. “If you want to avoid weeds in an area of the garden, you have to plant other plants there after weeding. If you leave the soil empty, the weeds will just grow back.”

The new approach has several advantages: it displaces pathogenic bacteria without the need for antibiotics, making it effective against antibiotic-resistant germs. It could also be used prior to surgical interventions, such as organ transplantations, where patients have to take immunosuppressant medications.

Further research is needed before this approach can be applied in humans, but the potential benefits are significant: a reduction in the use of antibiotics and improved health outcomes for everyone. One day, people may be able to swallow a capsule containing the vaccine and competitor bacteria, but until then, scientists will continue to refine their findings and push the boundaries of what is possible.

This research was made possible by financial support from the Basel Research Centre for Child Health, the National Centre of Competence in Research (NCCR) “Microbiomes” of the Swiss National Science Foundation, and a Consolidator Grant from the European Research Council (ERC) to Emma Slack.

Animals

“New Bat-Borne Viruses Discovered in China Pose Potential Pandemic Threat”

Two newly discovered viruses lurking in bats are dangerously similar to Nipah and Hendra, both of which have caused deadly outbreaks in humans. Found in fruit bats near villages, these viruses may spread through urine-contaminated fruit, raising serious concerns. And that’s just the start—scientists found 20 other unknown viruses hiding in bat kidneys.

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Scientists in China have made a groundbreaking discovery that could potentially alter our understanding of pandemics. Researchers from the Yunnan Institute of Endemic Disease Control and Prevention have found two new viruses in bats that are closely related to the deadly Nipah and Hendra viruses, which can cause severe brain inflammation and respiratory disease in humans.

The study, published in the open-access journal PLOS Pathogens, analyzed 142 bat kidneys from ten species collected over four years across five areas of Yunnan province. Using advanced genetic sequencing, the team identified 22 viruses – 20 of them never seen before. Two of these newly discovered viruses belong to the henipavirus genus, which includes Nipah and Hendra viruses known for their high fatality rates in humans.

The researchers’ findings are concerning because these henipaviruses can spread through urine, raising the risk of contaminated fruit and the possibility of the viruses jumping to humans or livestock. This highlights the importance of comprehensive microbial analyses of previously understudied organs like bat kidneys to better assess spillover risks from bat populations.

As bats are natural reservoirs for a wide range of microorganisms, including many notable pathogens that have been transmitted to humans, it is essential to conduct thorough research on these animals’ infectomes. This study not only broadens our understanding of the bat kidney infectome but also underscores critical zoonotic threats and highlights the need for comprehensive microbial analyses.

The authors emphasize that their findings raise urgent concerns about the potential for these viruses to spill over into humans or livestock, making it crucial for scientists, policymakers, and public health officials to work together to mitigate this risk. By analyzing the infectome of bat kidneys collected near village orchards and caves in Yunnan, the researchers have uncovered not only the diverse microbes bats carry but also the first full-length genomes of novel bat-borne henipaviruses closely related to Hendra and Nipah viruses identified in China.

Funding for this study came from various grants and programs, including the National Key R&D Program of China, Yunnan Revitalization Talent Support Program Top Physician Project, National Natural Science Foundation of China, and others. The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript.

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Bacteria

Unveiling the Secrets of Pandoraea: How Lung Bacteria Forge Iron-Stealing Weapons to Survive

Researchers investigating the enigmatic and antibiotic-resistant Pandoraea bacteria have uncovered a surprising twist: these pathogens don’t just pose risks they also produce powerful natural compounds. By studying a newly discovered gene cluster called pan, scientists identified two novel molecules Pandorabactin A and B that allow the bacteria to steal iron from their environment, giving them a survival edge in iron-poor places like the human body. These molecules also sabotage rival bacteria by starving them of iron, potentially reshaping microbial communities in diseases like cystic fibrosis.

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As scientists continue to unravel the mysteries of the human microbiome, a team of researchers has made a groundbreaking discovery about the lung bacteria Pandoraea. These microbes have long been associated with disease-causing properties, but new research reveals that they also possess remarkable survival strategies, including the ability to forge iron-stealing weapons to thrive in challenging environments.

At the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), researchers led by Elena Herzog have been studying Pandoraea bacteria, which are known to be pathogenic but also produce natural products with antibacterial effects. The team’s investigation has shed light on how these bacteria manage to survive in iron-poor environments within the human body.

Iron plays a vital role in living organisms, including bacteria, as it is essential for enzymes and the respiratory chain. However, in environments like the human body, where iron is scarce, microorganisms must adapt to compete for this essential resource. Pandoraea bacteria have developed a unique strategy by producing siderophores – small molecules that bind iron from their environment and transport it into the cell.

The researchers identified a previously unknown gene cluster called pan, which codes for a non-ribosomal peptide synthetase enzyme responsible for the production of siderophores. Through targeted inactivation of genes and advanced analytical techniques, they isolated two new natural products, Pandorabactin A and B, which can complex iron and play an important role in how Pandoraea strains survive.

Moreover, bioassays revealed that pandorabactins inhibit the growth of other bacteria by removing iron from these competitors. The researchers also analyzed sputum samples from cystic fibrosis patients, finding that the detection of the pan gene cluster correlates with changes in the lung microbiome. This suggests that pandorabactins could have a direct influence on microbial communities in diseased lungs.

While the study’s findings are still preliminary and not yet suitable for medical applications, they provide valuable insights into the survival strategies of Pandoraea bacteria and the complex competition for vital resources within the human body. As researchers continue to explore the intricacies of the microbiome, this discovery paves the way for further investigation and potentially innovative treatments in the future.

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Bacteria

A New Hope Against Multidrug Resistance: Synthetic Compound Shows Promise

Researchers have synthesized a new compound called infuzide that shows activity against resistant strains of pathogens.

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The World Health Organization (WHO) reports that antimicrobial resistance causes more than 1 million deaths every year and contributes to over 35 million additional illnesses. Gram-positive pathogens like Staphylococcus aureus and Enterococcus can cause severe hospital-acquired and community-acquired infections, making the development of effective treatments a pressing concern.

Researchers have recently discovered a synthetic compound called infuzide that shows promise against antimicrobial resistant strains of S. aureus and Enterococcus in laboratory and mouse tests. Infuzide was synthesized as part of a decade-long project by interdisciplinary researchers looking for ways to create compounds that could act against pathogens in ways similar to known pharmaceuticals.

“We started the project as a collaboration, looking for ways to synthesize compounds and connecting them with compounds that might have biological activities,” said medicinal chemist Michel Baltas, Ph.D., from the Laboratoire de Chimie de Coordination at the University of Toulouse in France. Baltas co-led the new work, along with Sidharth Chopra, Ph.D., from the CSIR-Central Drug Research Institute in Lucknow, India.

The researchers found that infuzide specifically attacks bacterial cells and is more effective than the standard antibiotic vancomycin in reducing the size of bacterial colonies in lab tests. In tests of resistant S. aureus infections on the skin of mice, the compound effectively reduced the bacterial population, with an even higher reduction when combined with linezolid.

While infuzide did not show significant activity against gram-negative pathogens, the researchers are exploring small changes to expand its antimicrobial activity. The simplicity of the chemical reactions involved in synthesizing infuzide also makes it easy to scale up production for new treatments.

In addition to its potential against multidrug resistance, the group has been investigating the effects of synthesized compounds on other infectious diseases, including tuberculosis. “We have many other candidates to make antimicrobial compounds,” Baltas said.

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