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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.

Bacteria

Insect Protein Holds Key to Stopping Bacterial Infections on Medical Implants

Scientists have reported use of antibacterial coatings made from resilin-mimetic proteins to fully block bacteria from attaching to a surface. A protein that gives fleas their bounce has been used to boot out bacteria cells, with lab results demonstrating the material’s potential for preventing medical implant infection.

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In a groundbreaking study led by researchers at RMIT University in Australia, a protein that gives fleas their remarkable elasticity has been used to prevent bacterial infection on medical implants. The resilin-mimetic proteins, which are derived from the insect resilin, have shown 100% effectiveness in repelling E.coli bacteria and human skin cells in lab conditions.

The study’s lead author, Professor Namita Roy Choudhury, said that this finding is a crucial step towards creating smart surfaces that stop dangerous bacteria, especially antibiotic-resistant ones like MRSA, from growing on medical implants. “This work shows how these coatings can be adjusted to effectively fight bacteria – not just in the short term, but possibly over a long period,” she added.

The potential applications of this research are vast and include spray coatings for surgical tools, medical implants, catheters, and wound dressings. The resilin-mimetic proteins have exceptional properties such as elasticity, resilience, and biocompatibility, making them ideal for many applications requiring flexible, durable materials and coatings.

Study lead author Dr Nisal Wanasingha said that the nano droplets’ high surface area made them especially good at interacting with and repelling bacteria. “Once they come in contact, the coating interacts with the negatively charged bacterial cell membranes through electrostatic forces, disrupting their integrity, leading to leakage of cellular contents and eventual cell death,” he explained.

Unlike antibiotics, which can lead to resistance, the mechanical disruption caused by the resilin coatings may prevent bacteria from establishing resistance mechanisms. Meanwhile, resilin’s natural origin and biocompatibility reduce the risk of adverse reactions in human tissues, making them more environmentally friendly than alternatives based on silver nanoparticles.

Future work includes attaching antimicrobial peptide segments during recombinant synthesis of resilin-mimics and incorporating additional antimicrobial agents to broaden the spectrum of activity. Transitioning from lab research to clinical use will require ensuring the formula’s stability and scalability, conducting extensive safety and efficacy trials, while developing affordable production methods for widespread distribution.

The study was in collaboration with the ARC Centre of Excellence for Nanoscale BioPhotonics and the Australian Nuclear Science and Technology Organisation (ANSTO). The team used ANSTO’s Australian Centre for Neutron Scattering facilities, and RMIT University’s Micro Nano Research Facility and Microscopy and Microanalysis Facility. The work was funded by the Australia India Strategic Research Fund, Australian Institute of Nuclear Science and Engineering top-up Postgraduate Research Award (PGRA) and supported by the Australian Research Council.

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Bacteria

Unlocking Better Cancer Treatment: Gut Bacteria Hold Key to Improving Detection and Treatment of Gastrointestinal Diseases

‘Biomarkers’ may help to improve detection and treatment of gastrointestinal diseases such as gastric cancer, colorectal cancer, and inflammatory bowel disease.

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Scientists have made a groundbreaking discovery that could revolutionize the way we diagnose and treat gastrointestinal diseases such as gastric cancer, colorectal cancer, and inflammatory bowel disease. Researchers have found a range of “biomarkers” – indicators of specific microorganisms or their byproducts in the gut – that can help improve detection and treatment of these conditions.

Using advanced machine learning and AI-based algorithms to analyze microbiome and metabolome datasets from patients with GC, CRC, and IBD, the research team identified common bacteria and metabolites linked to each disease. The study revealed that certain markers could predict not only one specific disease but also another, suggesting a shared underlying mechanism driving disease progression.

For example, in gastric cancer, researchers found bacteria from the Firmicutes, Bacteroidetes, and Actinobacteria groups were common, along with changes in metabolites like dihydrouracil and taurine. Some of these biomarkers were also relevant for IBD, indicating overlap between the diseases.

Similarly, in colorectal cancer, bacteria such as Fusobacterium and Enterococcus, and metabolites like isoleucine and nicotinamide, were significant, sometimes overlapping with those found in gastric cancer, suggesting possible shared pathways in disease development. In inflammatory bowel disease, bacteria from the Lachnospiraceae family and metabolites like urobilin and glycerate were important, with some of these markers also involved in cancer pathways.

The research team simulated gut microbial growth and metabolite fluxes, revealing significant metabolic differences between healthy and diseased states. This innovative approach could lead to the development of universal diagnostic tools to revolutionize the diagnosis and treatment of gastrointestinal conditions.

Dr Animesh Acharjee, lead co-author from the University of Birmingham, commented: “Current diagnostic methods like endoscopy and biopsies are effective but can be invasive, expensive, and sometimes miss diseases at early stages. Our analysis offers a better understanding of the underlying mechanisms driving disease progression and identifies key biomarkers for targeted therapies.”

The research team now plans to further explore the clinical applications of their findings, including the development of non-invasive diagnostic tests and targeted therapies based on the identified biomarkers. They also aim to validate their models in larger, diverse patient cohorts and investigate these biomarkers’ potential in predicting other related diseases.

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Bacteria

Uncovering the Secret Link Between Intestinal Bacteria and Aging Blood Vessels

The aging of the innermost cell layer of blood vessels leads to cardiovascular diseases. Researchers have now shown for the first time that intestinal bacteria and their metabolites contribute directly to vascular aging. As people age, the bacterial composition in their gut changes, resulting in fewer ‘rejuvenating’ and more harmful substances in the body.

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The connection between intestinal bacteria and cardiovascular disease has long been an area of interest for researchers. New findings from the University of Zurich have shed light on how these tiny microorganisms can influence our vascular health and contribute to the aging process. A team led by Soheil Saeedi has made a groundbreaking discovery that links the breakdown product of phenylalanine, phenylacetic acid, with accelerated cell aging in blood vessels.

In their study, Saeedi’s group analyzed data from over 7,000 healthy individuals aged between 18 and 95, as well as a mouse model of chronological aging. They found that the levels of phenylacetic acid increase with age, leading to cellular senescence in endothelial cells. This, in turn, causes blood vessels to stiffen and lose their function.

The researchers were able to identify Clostridium sp.ASF356 as the bacterium responsible for producing phenylacetic acid in the gut. By colonizing young mice with this bacterium, they observed increased levels of phenylacetic acid and signs of vascular aging. Conversely, when the bacteria were eliminated with antibiotics, the concentration of phenylacetic acid decreased, suggesting that intestinal bacteria play a role in accelerating the aging process.

However, the study also highlights the beneficial effects of certain intestinal bacteria on vascular health. Short-chain fatty acids, such as acetate, produced by fermentation of dietary fibers and polysaccharides in the gut, act as natural rejuvenating agents. Saeedi’s team demonstrated that adding sodium acetate can restore the function of aged vascular endothelial cells.

The research has significant implications for our understanding of how to regulate the aging process of the cardiovascular system. By modulating the microbiome through diet and other means, we may be able to slow down or even reverse vascular aging. The findings suggest that a diet rich in dietary fibers, antioxidant, and anti-inflammatory properties can boost the body’s own “fountain of youth,” while limiting intake of food and drinks high in phenylalanine, such as red meat and certain artificial sweeteners.

The study also paves the way for further research into developing medications to reduce phenylacetic acid levels in the body. Initial attempts using genetically modified bacteria have shown promise, offering a potential new approach to addressing cardiovascular disease.

In conclusion, the discovery of the link between intestinal bacteria and aging blood vessels has profound implications for our understanding of cardiovascular health and disease. By exploring the complex interaction between gut microbiota and the human body, we may uncover novel strategies for preventing or reversing vascular aging and reducing the risk of cardiovascular disease.

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