Tag Archives: antibiotics

Remarkable Images Reveal the Effects of Common Antibiotics on E. coli

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The above image displays untreated E. coli bacteria, with the lower image showing the effects of polymyxin B after 90 minutes.

Carolina Borrelli, Edward Douglas et al./Nature Microbiology

High-resolution microscopy unveils how polymyxins, a class of antibiotics, penetrate bacterial defenses, offering insights for developing treatments against drug-resistant infections.

Polymyxins serve as a last-resort option for treating Gram-negative bacteria responsible for serious infections like pneumonia, meningitis, and typhoid fever. “The priority pathogens identified by the top three health agencies globally are predominantly Gram-negative bacteria, highlighting their complex cell envelopes,” states Andrew Edwards from Imperial College London.

These bacteria possess an outer layer of lipopolysaccharides that functions as armor. While it was known that polymyxins target this layer, the mechanisms of their action and the reasons for inconsistent effectiveness remained unclear.

In a pivotal study, Edwards and his team employed biochemical experiments combined with nuclear power microscopy, capturing details at the nanoscale. They discovered that polymyxin B, amongst other treatments, actively targets E. coli cells.

Shortly after treatment commenced, the bacteria rapidly began releasing lipopolysaccharides.

Researchers observed that the presence of antibiotics prompted bacteria to attempt to assimilate more lipopolysaccharide “bricks” into their protective walls. However, this effort resulted in gaps, allowing antibiotics to penetrate and destroy the bacteria.

“Antibiotics are likened to tools that aid in the removal of these ‘bricks’,” Edwards explains. “While the outer membrane doesn’t entirely collapse, gaps appear, providing an entryway for antibiotics to access the internal membrane.”

The findings also elucidate why antibiotics occasionally fail: they predominantly affect active, growing bacteria. When in a dormant state, polymyxin B becomes ineffective as these bacteria do not produce armor strong enough to withstand environmental pressures.

E. coli images exposed to polymyxin B illustrate changes to the outer membrane over time: untreated, 15 mins, 30 mins, 60 mins, and 90 mins.

Carolina Borrelli, Edward Douglas et al./Nature Microbiology

Interestingly, researchers found that introducing sugar to E. coli could awaken dormant cells, prompting armor production to resume within 15 minutes, leading to cell destruction. This phenomenon is thought to be applicable to other polymyxins, such as polymyxin E, used therapeutically.

Edwards proposes that targeting dormant bacteria with sugar might be feasible, though it poses the risk of hastening their growth. “We don’t want bacteria at infection sites rapidly proliferating due to this stimulation,” he cautions. Instead, he advocates for the potential to combine various drugs to bypass dormancy without reactivating the bacteria.

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Source: www.newscientist.com

Antibiotics Generally Do Not Raise the Risk of Autoimmune Disorders

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Antibiotic use may impact the immune system adversely

City Image/Aramie

A comprehensive study involving over 6 million children reveals that those exposed to antibiotics prenatally or in early childhood do not generally face a heightened risk of developing autoimmune disorders during adolescence. However, the dynamics are quite intricate.

The notion that antibiotics may lead to autoimmunity dates back to the 1980s. David Strachan later proposed that the London’s Faculty of Hygiene and Tropical Medicine illustrates fewer infections in cleaner environments leading to a higher rate of childhood allergies.

This line of thought gave rise to the hygiene hypothesis, suggesting that limited early exposure to specific microorganisms fails to adequately train the immune system, which may react excessively to benign substances, leading to allergic responses or autoimmune disorders. Conditions like type 1 diabetes, inflammatory bowel disease, and lupus occur when immune cells mistakenly target the body’s own tissues.

Numerous studies since have demonstrated the crucial role of various microorganisms, particularly gut microbes, in shaping our immune responses. For instance, essential compounds for the maturation of specialized immune cells, such as regulatory T cells, play pivotal roles in preventing autoimmunity. This raises concerns over whether antibiotics that disrupt gut microbiota could facilitate the emergence of autoimmune diseases.

“Over time, numerous clinical studies, primarily using animal models, have substantiated the idea that antibiotics, or modifications to the gut microbiome, significantly affect immunity,” states Martin Kriegel from the University of Munster, Germany.

For instance, a 2016 study on mice illustrated that repeated antibiotic treatment at early life stages increased susceptibility to type 1 diabetes. Mice with genetic predisposition to this disorder were given their mothers’ breast milk alongside antibiotics thrice at 4 and 5 weeks old. Approximately 50% of the male and 80% of the female mice in this group developed type 1 diabetes by 30 weeks, while only about 25% of the male mice and 50% of the female mice that avoided antibiotics faced the same issue.

Similar correlations have surfaced in human research. An evaluation of over 10 million individuals released this year indicates that those prescribed antibiotics face an 40% higher risk of later developing inflammatory bowel disease. Additionally, a 2019 study involving over 110,000 participants linked antibiotic prescriptions to a 60% increased risk of developing rheumatic arthritis.

Conversely, other studies denote contrary findings. For example, a 2017 study involving over 15,000 children assessed for type 1 diabetes and celiac disease found no correlation between these conditions and antibiotic use prior to the age of four.

Recently, Eun-Young Choi from Sungkyunkwan University in Korea and her colleagues tracked the onset of six autoimmune conditions: type 1 diabetes, chronic pediatric arthritis, ulcerative colitis, Crohn’s disease, lupus, and Hashimoto’s disease. Around 1.5 million mothers received antibiotics during pregnancy, and a second group of 3.4 million children received similar treatment within the first six months post-birth, with 1.9 million treated with antibiotics.

After adjusting for variables like infection type, socioeconomic status, and gender, researchers found no collective correlation between antibiotic exposure in utero or early childhood and the likelihood of developing autoimmune conditions in adolescence.

Why do these findings differ so greatly? The gut microbiota’s complexity plays a significant role. Various factors influence it, making holistic explanations challenging. For instance, the studies referenced may fail to account for dietary influences on gut microbiota.

Different antibiotics also provoke varied effects. Choi’s study established a connection between broad-spectrum antibiotic use during pregnancy and subsequent development of Crohn’s disease in children. Additionally, the timing of antibiotic exposure appeared critical; antibiotics administered within two months of birth correlated with a 30% increased risk of Hashimoto’s disease.

This doesn’t imply that antibiotics should be entirely avoided. “When antibiotics are deemed necessary during pregnancy, it’s due to a belief that their benefits surpass potential risks,” asserts Christopher Zahn from the American University of Obstetricians in Washington, DC. For example, urinary tract infections can result in severe issues like preterm birth and low birth weight.

In fact, certain antibiotics may thwart autoimmunity. A 2018 study discovered that infections from pathogenic bacteria, notably Enterococcus gallinarum, induced autoimmunity in mice. Antibiotic treatment not only prevented mortality but also inhibited immune cells from attacking the organisms’ tissues.

“Thus, the situation is immensely complicated,” remarks Kriegel.

However, the latest findings should alleviate concerns for pregnant individuals and those with young children, reassures Zahn.

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Source: www.newscientist.com

New Research Suggests Caffeine May Decrease Effectiveness of Some Antibiotics

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Researchers from the University of Tübingen and Würzburg have found that components of our everyday diet, including caffeine, can influence bacterial resistance to antibiotics. They observed that E. coli bacteria adjust complex modulation cascades to respond to chemical signals from their immediate environment, potentially impacting the effectiveness of antibiotics.

This diagram illustrates a 3D computer-generated image of a group of E. coli. Image credits: James Archer, CDC.

In a systematic screening, Professor Ana Rita Brochado and her team examined the effects of 94 different substances, including antibiotics, prescription medications, and dietary components, on the expression of critical gene regulators and transport proteins in E. coli bacteria.

Transport proteins function as pores and pumps within bacterial membranes, regulating the movement of substances in and out of cells.

A precisely adjusted balance of these mechanisms is crucial for bacterial survival.

“Our data reveals that certain substances can exert subtle yet systematic influences on gene regulation in bacteria,” explained doctoral student Christoph Vincefeld.

“These findings indicate that even everyday substances, which lack direct antibacterial properties, like caffeinated beverages, can impact specific gene regulators that modulate transport proteins, thereby modifying bacterial import and composition.”

“Caffeine initiates a cascade of events starting with the lob gene regulator, resulting in alterations in several transport proteins in E. coli. This effect reduces the uptake of antibiotics such as ciprofloxacin,” Professor Rita Brochado added.

“Consequently, this diminishes the antibiotic’s effectiveness.”

The researchers characterize this effect as an “antagonistic interaction.”

The diminishing efficacy of certain antibiotics also applies to salmonella enterica, a close relative of E. coli.

This suggests that even similar bacterial species can react differently to identical environmental cues, likely due to variations in transport pathways and how they contribute to antibiotic absorption.

“This foundational study on the effects of commonly consumed substances highlights the significant role of science in addressing and resolving real-world challenges,” stated Professor (Doshisha) Karla Pollmann.

“This research contributes meaningfully to the understanding of what is termed ‘low-level’ antibiotic resistance, which does not result from classical resistance genes but rather through regulation and environmental adaptation.”

“These insights could influence future treatment strategies involving drug or dietary component modifications.”

The results will be published online in PLOS Biology.

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C. Vincefeld et al. 2025. Systematic screens reveal regulatory contributions to chemical cues in E. coli. Plos Biol 23(7): E3003260; doi: 10.1371/journal.pbio.3003260

Source: www.sci.news

AI Uncovers 386 Potential Antibiotics in Animal Venom

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University of Pennsylvania researchers used a deep learning tool named Apex to explore a worldwide venom dataset in search of new antibiotic candidates.

Guan et al. Vococcus is a rich source of previously hidden antibiotic scaffolds, showing that merging experimental validation with extensive computational mining can enhance the search for urgently needed antibiotics. Image credits: Guan et al., doi: 10.1038/s41467-025-60051-6.

The increasing prevalence of antibiotic-resistant pathogens, especially Gram-negative bacteria, underscores the critical demand for new treatments.

Venococcus represents a vast, largely untapped source of bioactive molecules with potential antibacterial properties.

In their recent study, researcher César de La Fuente and his team analyzed a comprehensive database containing 16,123 poison proteins and over 40 million poison-encoded peptides via a vertex deep learning model.

The algorithm successfully pinpointed 386 candidate peptides that differ in structure and function from known antimicrobial peptides.

“These poisons are evolutionary wonders, yet their antibacterial capabilities have not been thoroughly examined,” said Dr. de la Fuente.

“Apex can rapidly explore extensive chemical landscapes, identifying exceptional peptides that combat some of the most stubborn pathogens worldwide.”

From the potential candidates selected by AI, scientists synthesized 58 peptide variants for laboratory assessment.

Remarkably, 53 of these demonstrated efficacy against drug-resistant bacteria such as E. coli and Staphylococcus aureus, at doses safe for human red blood cells.

“By combining computational analysis with traditional laboratory techniques, we achieved one of the most thorough antibiotic studies to date,” noted Dr. Marcelo Torres, co-author of the research.

“The platform has mapped over 2,000 novel antibacterial motifs, enhancing its capacity to eliminate or suppress bacterial growth through short, specific amino acid sequences within proteins or peptides.”

“Our team is now advancing the top peptide candidates towards the development of new antibiotics, optimizing them through medicinal chemistry modulation.”

results will be published in the journal Nature Communications.

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C. Guan et al. 2025. A global assessment of venom data for antibacterial discovery using artificial intelligence techniques. Nat Commun 16, 6446; doi:10.1038/s41467-025-60051-6

Source: www.sci.news

Preserving Gut Health: Using Gut-Friendly Antibiotics to Treat Lyme Disease

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Lyme disease can spread to people through mites

Heico Birth/Shutterstock

Antibiotics commonly used to absorb pneumonia remove Lyme disease mice at doses 100 times lower than standard antibiotic therapy. This small dose was combined with the targeted effect of the drug on infection, meaning that the animal’s gut microbiota was largely unaffected.

Lyme disease is caused by bacteria in the genus Borelia It spreads mostly among birds and small rodents, but people can get infected via the bites of mites that have given the blood of such animals. Infections generally lead to flu-like symptoms and a “bull” rash. Without treatment, it can cause serious long-term complications such as fatigue and pain.

Standard treatment involves taking the antibiotic doxycycline twice daily at high doses for up to three weeks. This will stop the production of the proteins needed for bacteria to survive, but will not selectively target them Borelia seed. “It will cause chaos normally [gut] It says microbiome. Brandon Footlas At Northwestern University, Illinois.

Looking for a more selective alternative, Jutras and his colleagues first tested how effective it is to have more than 450 antibiotics all approved by the US Food and Drug Administration. Borrelia burgdorferi – The most common type of lab dishes that causes Lyme disease.

They then evaluated how best-performing drugs affected the growth of harmless or beneficial bacteria commonly found in people and mouse visceral organs, such as certain strains. E. coli. This revealed that piperacillin is associated with penicillin, commonly used in the treatment of pneumonia and is the most selective target. B. burgdorferi.

Next, the researchers injected 46 mice. B. burgdorferi. Three weeks later, they treated the animals with various doses of either doxycycline or piperacillin for a week. The researchers found that mice received either high doses of doxycycline or 100 times lower doses of piperacillin, with no signs of infection.

They also analyzed stools from mice before and after antibiotic treatment and found that low doses of piperacillin had little effect on bacterial levels. B. burgdorferi In the gut, high doses of doxycycline significantly altered the gut microbiota.

This is probably due to the low amount of antibiotics, which has less impact on intestinal microbial diversity and is the target action of piperacillin. “We found that using piperacillin is targeting certain proteins. B. burgdorferiit is very efficient to kill this Lyme disease agent at low concentrations, not other bacteria, to survive,” says Jutras.

But mice can respond differently to antibiotics than people, John Ocotte at Johns Hopkins University in Maryland. For example, they often break down the drug faster, which can change its effectiveness. The Jutras team hopes to test piperacillin in human Lyme disease tests in the coming years.

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Source: www.newscientist.com

Two antibiotics found in Arctic marine bacteria by scientists

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A research team from Finland and Norway has identified two candidate anti-toxic compounds against enteric pathogens. E. coli Marine actinomycete strains from the bacterial metabolite (EPEC) infection Cochlea and Rhodococcus From the Arctic Ocean.

Strain T091-5 of this genus RhodococcusImages/Photos Courtesy of: Pylkkö others., doi: 10.3389/fmicb.2024.1432475.

“We show that advanced screening assays can identify anti-toxic and antibacterial metabolites from actinomycete extracts,” says Professor Paivi Tamela from the University of Helsinki.

“We discovered compounds in the Arctic actinomycete that inhibit virulence without affecting EPEC growth, as well as compounds that inhibit growth.”

Professor Tamera and his colleagues have developed a series of new methods that allow them to simultaneously test the antitoxic and antibacterial effects of hundreds of unknown compounds.

They targeted a strain of EPEC that causes severe, sometimes fatal, diarrhea in children under the age of 5, especially in developing countries. EPEC attaches to cells in the human intestine and causes disease.

Once EPEC attaches to these cells, it injects so-called “virulence factors” into the host cell that hijack its molecular machinery and ultimately kills the cell.

The compounds tested were extracted from four species of actinomycetes isolated from invertebrates collected in the Arctic waters off the coast of Svalbard during an expedition by a Norwegian research vessel. Cronprince Haakon August 2020.

These bacteria were cultured, the cells were extracted, and their contents were separated into fractions.

Each fraction was then tested in vitro against EPEC attached to cultured colon cancer cells.

The researchers discovered two previously unknown compounds with strong anti-toxic or anti-bacterial activity: one from an unknown strain of the genus (called T091-5); Rhodococcusand another strain from an unknown strain of this genus (T160-2). Cochlea.

These compounds exhibited two complementary biological activities.

First, it inhibits the formation of the so-called “actin pedestal” by EPEC bacteria, a key step in the attachment of this pathogen to the host intestinal wall.

The second is to block EPEC binding to so-called Tir receptors on the surface of host cells, a necessary step to rewire intracellular processes and cause disease.

Unlike compounds in T160-2, compounds in T091-5 did not slow the growth of EPEC bacteria.

This means that T091-5 is the most promising of the two strains, as EPEC is unlikely to eventually develop resistance to its antivirulence effects.

Using advanced analytical techniques, the authors determined that the active compounds in T091-5 were likely phospholipids, a type of fatty phosphorus-containing molecule that plays an important role in cellular metabolism.

“The next steps are to optimise the culture conditions for compound production and to isolate sufficient quantities of each compound to elucidate their structures and further explore their respective biological activities,” Prof Tamera said.

of Survey results Published in today's journal The cutting edge of microbiology.

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Tuomas Pirko others2024. Bioprospecting EPEC virulence inhibitors from metabolites of an Arctic marine actinomycete. Front. Microbiol 15;doi: 10.3389/fmicb.2024.1432475

Source: www.sci.news

Artificial Intelligence identifies novel antibiotics effective against drug-resistant bacteria

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Methicillin-resistant Staphylococcus aureus (MRSA)

Shutterstock / Katerina Conn

Artificial intelligence has contributed to the discovery of new classes of antibiotics that can treat infections caused by drug-resistant bacteria. This could help fight antibiotic resistance, which claimed more than 1.2 million lives in 2019, and that number is expected to increase in the coming decades.

A new antibiotic compound has proven to be a promising treatment for both methicillin resistance and tolerance in tests in mice. Staphylococcus aureus (MRSA) and vancomycin resistance Enterococcus – Bacteria that have developed resistance to drugs commonly used to treat MRSA infections.

“our [AI] The model not only tells us which compounds have selective antibiotic activity, but also why in terms of their chemical structure. ” Felix Wong at the Broad Institute of MIT and Harvard University in Massachusetts.

Wong and colleagues aimed to show that AI-driven drug discovery can go beyond identifying specific targets to which drug molecules can bind to predicting the biological effects of entire classes of drug-like compounds.

First, we tested the effects of over 39,000 compounds. Staphylococcus aureus Three types of human cells: liver, skeletal muscle, and lung. The result was training data for the AI ​​model to learn the chemical atoms and bond patterns of each compound. This has enabled AI to predict both the antibacterial activity and potential toxicity of such compounds to human cells.

The trained AI model then analyzed 12 million compounds through computer simulations and found 3,646 compounds with ideal drug-like properties. Additional calculations identified chemical substructures that could explain the properties of each compound.

By comparing such substructures of different compounds, researchers identified a new class of potential antibiotics and ultimately two non-antibiotics that can kill both MRSA and vancomycin-resistant bacteria. discovered a toxic compound Enterococcus.

Finally, researchers used mouse experiments to demonstrate the effectiveness of these compounds in treating skin and thigh infections caused by MRSA.

Only a few new classes of antibiotics, such as oxazolidinones and lipopeptides, have been discovered to be effective against both MRSA and vancomycin-resistant bacteria. Enterococcus – and says resistance to such compounds is increasing. james collins at the Broad Institute, where he co-authored the study.

“Our research has identified one of the few new classes of antibiotics in 60 years that complements other antibiotics,” he says.

Researchers are working to design entirely new antibiotics and discover other new drug classes, such as compounds that selectively kill aging and damaged cells involved in conditions such as osteoarthritis and cancer. are starting to use this AI-driven approach.

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Source: www.newscientist.com