Category: Antibiotics

Categories : Antibiotics Diet and NutritionTags :

Honey from Australian Wildflowers has Potent Power to Kill Bacteria

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Photo by Benyamin Bohlouli on Unsplash

Kenya Fernandes, University of Sydney

Before antibiotics and antiseptics, healers across ancient Egypt, Greece, and China reached for honey to treat wounds. Archaeological evidence shows humans have been harvesting and collecting honey for thousands of years – and for much of that time, we understood it to be more than just food.

Today, honey sits in most kitchen cupboards as a perfectly ordinary pantry staple. But honey has never entirely shed its medicinal reputation. And modern research shows us why: it possesses genuine antimicrobial properties, capable of killing or inhibiting a wide range of bacteria, including drug-resistant strains.

This matters now more than ever. Antimicrobial resistance – where bacteria evolve to survive drugs designed to kill them – is one of the defining public health crises of our time. Infections caused by these resistant microbes are becoming harder and more expensive to treat, creating an urgent need for alternative therapies.

Our new study, published in the journal MicrobiologyOpen, shows honeys from Australia’s native flora might be a big part of the solution.

What did we do?

We analysed 56 honey samples collected from more than 35 apiaries across New South Wales. Many samples came from landscapes recovering from the 2019–2020 bushfires. Most were derived from native Australian plants such as eucalyptus, leptospermum and melaleuca.

We tested the honeys against two common bacterial pathogens: Staphylococcus aureus (golden staph) and E. coli – both among the six leading causes of deaths associated with antibiotic resistance. For each sample we measured the minimum concentration needed to stop bacterial growth. The lower the concentration, the more potent the honey.

We also carried out comprehensive chemical profiling, measuring sugars, organic acids, amino acids, enzymes and a wide range of plant-derived compounds. Statistical and machine-learning analyses helped us identify which chemical features best explained antibacterial strength.

What did we find?

More than three-quarters of the honey samples stopped bacterial growth even when the honeys were diluted to 10% or less. This places Australian native flora honeys alongside some of the world’s most potent varieties.

The most striking factor was floral diversity.

Honeys from mixed floral sources – where bees foraged across multiple native plant species rather than a single species – were consistently the most antimicrobial.

This potency wasn’t due to any single compound but to a chemically rich combination.

Multiple bioactive factors – substances that have a measurable effect on living cells or tissues – worked together to inhibit bacteria. These included naturally produced hydrogen peroxide, plant-derived phenolic compounds (naturally occurring chemicals that plants produce as part of their own defence systems), and antioxidants.

When bacteria encounter honey, this combination acts on several fronts at once. The low moisture content draws water out of bacterial cells, while the acidity disrupts their metabolism. Hydrogen peroxide damages their cellular structures, and phenolic and antioxidant compounds interfere with their ability to function and reproduce.

The strength of mixed floral honeys may also reflect the health of the bees themselves.

Access to diverse forage keeps colonies well nourished. And healthier bees produce more biologically active honey as their enzymes help integrate and activate the plant compounds into a complex antimicrobial mixture.

What does this mean for antimicrobial resistance?

Honey won’t replace antibiotics for serious or systemic infections.

But for topical applications – chronic wounds, burns, or surgical site infections – it is a genuinely promising option. Because honey attacks bacteria through multiple simultaneous mechanisms, resistance is far less likely to emerge than with single-target drugs. Our team is now exploring these applications in more detail.

Australia is particularly well-placed to lead in bioactive honey production. Around 70% of Australian honey comes from native plants. These plants are found not only in forests but also across farmland, regional landscapes, and urban green spaces.

Our findings show that prioritising floral diversity over monoculture isn’t just good for ecosystems – it produces more potent honey. With the beekeeping industry under serious pressure from bushfires, floods, and now the varroa mite, protecting and restoring florally-rich landscapes is critical: for bee health, for industry resilience, and for expanding our natural antimicrobial toolkit.

In the meantime, the next jar of Australian honey you buy may just be doing more good than you realise.

Kenya Fernandes, Research Fellow, Faculty of Science, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Antibiotics Injury & TraumaTags :

New Device Sprays Antibiotics Deep into Wounds

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The new device sprays mist to treat deep wound infections without causing kidney damage

Hongmin Sun demonstrating the new device.

A University of Missouri researcher has unveiled a safer, smarter way to fight drug-resistant infections. Hongmin Sun, an associate professor in the School of Medicine, demonstrated that a spray-mist device can deliver last-resort antibiotics directly into infected tissue without the harmful side effects often caused by delivery via the bloodstream.

In a recent study, researchers worked with an industry partner to use a needle-free device to treat methicillin-resistant Staphylococcus aureus (MRSA), a dangerous bacterium that has become resistant to many common antibiotics.

The device successfully delivered the common last-resort antibiotic vancomycin deep into infected tissue without typical side effects such as kidney damage. Unlike topical creams or ointments that are easily wiped away or bloodstream delivery that risks organ damage, the spray-mist technology pushed the medicine through the skin to successfully treat the infection.

Sun collaborated with former Mizzou researcher Lakshmi Pulakat, now a professor of medicine at Tufts University, and Droplette Inc. to use the patented device for antibiotic delivery. The findings pave the way for future clinical trials as researchers seek FDA approval.

The team is hopeful the spray-mist device might one day be used in wound care in challenging settings.

“Whether it’s people with diabetic foot ulcers or soldiers hurt in battle, we wanted to come up with a new approach to treat these severely infected wounds in a more targeted way,” Sun said. “This can be a game-changing therapy for treating those with severely infected wounds.”

Pulakat said the technology is an example of compassionate care.

“This method of delivering last-resort antibiotics could prevent countless amputations and help save lives,” she said. “Dr. Sun is an internationally recognized expert in the field of pathogenic microbiology, and our collaboration with an industry partner has helped make this translational research possible.”

The study, “Preventing nephrotoxicity of vancomycin and attenuating deep tissue infections by methicillin-resistant Staphylococcus aureus via needle-free drug delivery by the Droplette micromist technology device” was published in Military Medicine.

By Brian Consiglio

Source: University of Missouri

Categories : Antibiotics Mental HealthTags :

A Common Antibiotic may Reduce Schizophrenia Risk in Young People

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Photo by Danilo Alvesd on Unsplash

A commonly prescribed antibiotic could help reduce the risk of some young people developing schizophrenia, new research suggests. Experts found that patients of adolescent mental health services who were treated with the antibiotic doxycycline were significantly less likely to go on to develop schizophrenia in adulthood compared with patients treated with other antibiotics.

The researchers say that the findings highlight the potential to repurpose an existing, widely used medication as a preventive intervention for severe mental illness.

Lower risk

Schizophrenia is a severe mental disorder that typically emerges in early adulthood and is often associated with hallucinations and delusional beliefs.

To better understand potential ways of preventing the condition, researchers from the University of Edinburgh, in collaboration with the University of Oulu and University College Dublin, applied advanced statistical modelling to large-scale healthcare register data from Finland.

The team analysed data from more than 56 000 adolescents attending mental health services who had been prescribed antibiotics. They found that those treated with doxycycline had a 30–35% lower risk of developing schizophrenia than peers who received other antibiotics.

The researchers hypothesised that the protective effect could be linked to doxycycline’s impact on inflammation and brain development.

Reduce inflammation

Doxycycline is a broad-spectrum antibiotic commonly used to treat infections and acne. Previous studies suggest it can reduce inflammation in brain cells and influence synaptic pruning – a natural process where the brain refines its neural connections. Excessive pruning has been associated with the development of schizophrenia.

Further analyses showed that the lower risk wasn’t simply because the young people may have been treated for acne rather than having infections, and was unlikely to be explained by other hidden differences between the groups.

The study is published in the American Journal of Psychiatry. It involved researchers from the University of Edinburgh, the University of Oulu, University College Dublin, and St John of God Hospitaller Services Group, and was funded by the Health Research Board.

As many as half of the people who develop schizophrenia had previously attended child and adolescent mental health services for other mental health problems. At present, though, we don’t have any interventions that are known to reduce the risk of going on to develop schizophrenia in these young people. That makes these findings exciting.

Because the study was observational in nature and not a randomised controlled trial, it means we can’t draw firm conclusions on causality, but this is an important signal to further investigate the protective effect of doxycycline and other anti-inflammatory treatments in adolescent psychiatry patients as a way to potentially reduce the risk of developing severe mental illness in adulthood.

 Professor Ian Kelleher, Professor of Child and Adolescent Psychiatry at the University of Edinburgh

Source: University of Edinburgh

Categories : AntibioticsTags :

Study Finds High Rates of Antibiotic-resistant Bacteria in Raw Milk

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In Pakistan, 50% of strains of a common milk bacterium, Staphylococcus epidermidis, were multi-drug resistant

Cultured Staphylococcus epidermidis isolates from raw milk samples on MSA. Image credit: Inamullah and colleagues, Abdul Wali Khan University Mardan, Pakistan, CC-BY 4.0

Raw cow and sheep milk is frequently contaminated with antibiotic-resistant bacteria that could pose a threat to human and animal health, reports a new study led by Tahir Usman of Abdul Wali Khan University Mardan, Pakistan, published November 12, 2025 in the open-access journal PLOS One.

In Pakistan, over 95% of milk is consumed in its raw form, which has not been pasteurized to kill off harmful bacteria. Milk can become contaminated by bacteria through improper handing or from infections in the teat, called subclinical mastitis. The overuse of antibiotics to treat subclinical sumastitis has led to the emergence of multidrug-resistant bacterial strains, which could then be transmitted to humans through raw milk.

In the new study, researchers investigated the risk posed by Staphylococcus epidermidis, a subclinical mastitis-causing bacteria that often does not lead to visible symptoms in the cow, but results in contaminated, lower-quality milk. They collected 310 milk samples, about half from cattle and half from ewes, and tested them for subclinical mastitis. They also isolated strains of Staphylococcus epidermidis from the milk samples and screened them for antibiotic resistance. About one quarter of the samples showed evidence of subclinical mastitis and almost 13% (1 in 8) were contaminated with Staphylococcus epidermidis. Strikingly, 95% of Staphylococcus epidermidis bacteria isolated from the milk were resistant to penicillin and erythromycin, and half were resistant to three or more antibiotics.

In humans, Staphylococcus epidermidis is a common, generally harmless inhabitant of the skin, but the researchers point out that multi-drug resistant Staphylococcus epidermis bacteria in raw milk could spread antimicrobial resistance to more harmful pathogens, like Staphylococcus aureus, the MRSA pathogen.

The study’s findings underscore the high rates of subclinical mastitis in cattle and ewes, and indicate that Staphylococcus epidermidis might be an important pathogen impacting both animal health and food safety. The high rates of antibiotic resistance observed in the samples also emphasize the urgent need for improved antibiotic stewardship in agriculture to prevent the rise of multi-drug resistant strains.

The authors add: “The presence of multidrug-resistant Staphylococcus epidermidis in raw milk highlights how on-farm antibiotic use directly shapes public health risks. These findings emphasize the urgent need for responsible antibiotic use and improved hygiene practices in the dairy sector to reduce the risk of antimicrobial resistance transmission through the food chain.”

Provided by PLOS

Categories : Antibiotics Respiratory DiseasesTags :

Targeted Steroid Use Might Offer a Universal Complementary Treatment for TB

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Tuberculosis bacteria. Credit: CDC

While steroids like dexamethasone are used in certain tuberculosis cases (eg, TB meningitis), their impact on immune cells is not well understood. Given the renewed interest in the steroid dexamethasone, as a host-directed treatment during the COVID-19 pandemic, a Trinity College Dublin team provides evidence that treating patients with steroids may enhance the function of their macrophages to kill the mycobacteria, while diminishing pathways of inflammatory damage. The study is published now in the journal Scientific Reports.

The team’s goal was to determine whether dexamethasone impacts the macrophage’s ability to fight TB. Although glucocorticoids can reactivate TB, they are paradoxically the only adjunctive host-directed therapies that are recommended by the World Health Organization for TB. Steroids are given to patients alongside antimicrobials in certain circumstances, however, scientists don’t fully understand the effect of these drugs on the immune system, especially innate immune cells such as macrophages.

The researchers studied immune cells called macrophages derived from the blood of healthy volunteers or isolated from lung fluid donated by patients undergoing routine bronchoscopies. By treating and infecting these macrophages in the lab with Mycobacterium tuberculosis (Mtb), the scientists could examine and understand how dexamethasone affects the immune response that protects the lungs during infection.

Key findings from the study

  • Dexamethasone a potent glucocorticoid reduces glycolysis in human lung and blood derived macrophages. This reduces the amount of energy available in the cell.
  • Dexamethasone reduced the production of both pro and anti-inflammatory cytokines measured in the study, IL-1β, TNF, IL-6, IL-8 and IL-10. Although helpful for immunity, limiting the production can also limit damage from excessive inflammation.
  • Mtb-infected macrophages have increased survival when they were treated with dexamethasone. This suggests that dexamethasone may protect macrophages from dying due to the harmful effects of infection or detrimental immune responses to infection.
  • Dexamethasone reduces bacterial burden in infected macrophages, and we have identified that this is at least partly mediated by autophagy and phagosomal acidification. Dexamethasone can enhance the macrophages’ ability to degrade and clear bacteria helping to overcome infection with Mtb.

This study identifies that macrophages from different sources have differential responses to glucocorticoids. This highlights that tissue origin can influence how macrophages react to drugs, which may be important for targeting treatment strategies. This is one of the first studies to show that dexamethasone can reduce inflammation while preserving or enhancing antimicrobial function in primary human lung macrophages infected with Mtb.

How could this research change a patient’s life?

The findings support the use of steroids as an extra therapy in conjunction with existing antimicrobial therapies in TB treatment, especially in cases with excessive inflammation. Steroids might also be useful with antimicrobials in TB preventative therapy, to reduce progression from latent TB infection to active TB disease. This study opens avenues for macrophage-targeted steroid therapies that balance inflammation control with antimicrobial defence.

For now, researchers hope this study will hasten the recovery of TB patients who experience debilitating symptoms, often for months into existing therapy.

Dr Donal Cox, Senior Research Fellow, Clinical Medicine, Trinity College Dublin said:

“Our study shows that dexamethasone, which is known to dampen inflammation, can also help macrophages fight tuberculosis more effectively. This challenges the assumption that steroids always suppress immunity and opens the door to smarter, targeted adjunctive therapies that balance inflammation control with antimicrobial defence.”

Prof Joseph Keane, Professor of Medicine, Trinity College Dublin and Consultant Respiratory Physician, St James Hospital said:

“In clinical practice, steroids are the most under-used adjunctive therapy for TB. We often rely on steroids to manage inflammation in tuberculosis, particularly in severe forms like TB meningitis. What’s reassuring from this study, is that dexamethasone not only tempers inflammation but also appears to support the macrophage’s ability to control infection. This study provides new evidence to help us redefine steroid use in TB care—targeting inflammation without compromising antimicrobial defence.”

Next steps for this research

Developing steroid therapies that can be specifically targeted to lung macrophages via mechanisms such as inhaled nanoparticles might be an option to translating this into better therapy. The team also wants to identify how steroids altered different metabolic pathways in human lung macrophages and not in blood derived macrophages so they can exploit this to make steroid therapies better in the future.

Source: Trinity College Dublin

Categories : AntibioticsTags :

Amazing Images Show How Antibiotics Shred Bacterial Armour

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Bacteria response to antibiotics

UK researchers have shown for the first time in stunning detail how life-saving antibiotics act against harmful bacteria. The team, led by UCL and Imperial College London, has shown for the first time how a class of antibiotics called polymyxins are able to pierce the armour of E. coli and kill the microbes. 

The findings, published in the journal Nature Microbiology, could lead to new treatments for bacterial infections – especially urgent since drug-resistant infections already kill more than a million people a year.

Polymyxins were discovered more than 80 years ago and are used as a last-resort treatment for infections caused by “Gram negative” bacteria.

These bacteria have an outer surface layer that acts like armour and prevents certain antibiotics from penetrating the cell. Polymyxins are known to target this outer layer, but how they disrupt it and then kill bacteria is still not understood.

Through capturing these incredible images of single cells, we’ve been able to show that this class of antibiotics only work with help from the bacterium, and if the cells go into a hibernation-like state, the drugs no longer work – which is very surprising

Dr Andrew Edwards Department of Infectious Disease

In the new study, the research team revealed in high-resolution images and biochemical experiments how the antibiotic Polymyxin B rapidly caused bumps and bulges to break out on the surface of an E. coli bacterial cell.

These protrusions, which appeared within minutes, were followed by the bacterium rapidly shedding its outer armour.

The antibiotic, the researchers concluded, had triggered the cell to produce and shed its armour.

The more the cell tried to make new amour, the more it lost the amour it was making, at such a rate that it left gaps in its defences, allowing the antibiotic to enter the cell and kill it.

However, the team found that this process – protrusions, fast production and shedding of armour, and cell death – only occurred when the cell was active. In dormant (sleeping) bacteria, armour production is switched off, making the antibiotic ineffective.

Co-senior author Dr Andrew Edwards, from the Department of Infectious Disease at Imperial College London, said: “For decades we’ve assumed that antibiotics that target bacterial armour were able to kill the microbes in any state, whether they’re actively replicating or they were dormant. But this isn’t the case.

“Through capturing these incredible images of single cells, we’ve been able to show that this class of antibiotics only work with help from the bacterium, and if the cells go into a hibernation-like state, the drugs no longer work – which is very surprising.”

Becoming dormant allows bacteria to survive unfavourable conditions such as a lack of food. They can stay dormant for many years and “wake up” when conditions become more favourable. This can allow bacteria to survive against antibiotics, for instance, and reawaken to cause recurrent infections in the body.

Co-senior author Professor Bart Hoogenboom, based at the London Centre for Nanotechnology at UCL, said: “Polymyxins are an important line of defence against Gram-negative bacteria, which cause many deadly drug-resistant infections. It is important we understand how they work.

“Our next challenge is to use these findings to make the antibiotics more effective. One strategy might be to combine polymyxin treatment – counterintuitively – with treatments that promote armour production and/or wake up ‘sleeping’ bacteria so these cells can be eliminated too.

“Our work also shows we need to take into account what state bacteria are in when we are assessing the effectiveness of antibiotics.”

The E. coli cells were imaged at the London Centre for Nanotechnology at UCL. A tiny needle, only a few nanometres wide, was run over the bacterial cell, “feeling” the shape to create an image (a technique called atomic force microscopy) at much higher resolution than would be possible using light.

Co-author Carolina Borrelli, a PhD student at the London Centre for Nanotechnology at UCL, said: “It was incredible seeing the effect of the antibiotic at the bacterial surface in real-time. Our images of the bacteria directly show how much polymyxins can compromise the bacterial armour. It is as if the cell is forced to produce ‘bricks’ for its outer wall at such a rate that this wall becomes disrupted, allowing the antibiotic to infiltrate.”

The team compared how active (growing) and inactive E. coli cells responded to polymyxin B in the lab, finding that the antibiotic efficiently eliminated active cells but did not kill dormant cells.

They also tested the E. coli cells’ response with and without access to sugar (a food source that wakes up dormant cells). When sugar was present, the antibiotic killed previously dormant cells, but only after a delay of 15 minutes – the time needed for the bacteria to consume the sugar and resume production of its outer armour.

In conditions where the antibiotic was effective, the researchers detected more armour being released from the bacteria. They also observed the bulges occurring across the surface of the cell.

In conditions where it was ineffective, the antibiotic bound itself to the outer membrane but caused little damage.

Co-author Dr Ed Douglas, from Imperial, said: “We observed that disruption of the outermost armour of the bacteria only occurred when the bacteria were consuming sugar. Once we knew that, we could quickly figure out what was happening.”

Co-author Professor Boyan Bonev, of the University of Nottingham, said: “Working together has given us unique insights into bacterial physiology and morphology under stress that have remained hidden for decades. Now we understand better the weak points of bacteria.”

Source: Imperial College London

Categories : AntibioticsTags :

Could Slime Mould Microbes Be a Source of Potent Antimicrobials?

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Photo by National Cancer Institute on Unsplash

The cellular slime mold Dictyostelium discoideum is a soil microbe that produces diverse natural products with potential antibiotic activity. Previously, three chlorinated compounds had been detected in Dictyostelium, but only the most abundant compound (CDF-1) was identified and shown to be almost as effective an antimicrobial as ampicillin.  In research published in FEBS Open Bio, investigators optimised lab culture conditions of Dictyostelium cells to boost the levels of low-abundance chlorinated compounds and to characterise their antimicrobial properties.

The optimized culture conditions took advantage of propionic acid and zinc supplementation to increase the yield of the chlorinated compounds, leading to the identification of CDF-2 and CDF-3 in addition to CDF-1. The molecular structure of CDF-2 and CDF-3 was similar to that of CDF-1, aside from the length of a molecular structure called an acyl side chain. When their antibacterial activity was tested, similarly to CDF-1, CDF-2 and CDF-3 exhibited stronger activity against Gram-positive bacteria than ampicillin but limited activity against Gram-negative bacteria.

Because these compounds are conserved across distantly related Dictyostelium species, CDFs may fulfill a critical role in protecting against harmful bacteria.

“Soil presents both opportunities and dangers for the Dictyostelium amoeba, and we believe this amoeba responds by producing specialised chemicals to attract, repel, or eliminate friends, prey, and predators. We are just starting to discover these chemicals, including this new, potent antibiotic,” said corresponding author Tamao Saito, PhD, of Sophia University, in Japan.

Source: Wiley

Categories : Antibiotics PaediatricsTags :

‘Alarming’ Rise in Newborn Babies with Antibiotic-resistant Infections, Researchers Find

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Photo by Christian Bowen on Unsplash

Researchers are calling for an urgent overhaul of diagnostic and treatment guidelines for infections in newborn babies, after a University of Sydney-led study revealed frontline treatments for sepsis are no longer effective to treat the majority of bacterial infections. 

The study, published in The Lancet Regional Health – Western Pacific, analysed almost 15 000 blood samples collected from sick babies in 2019 and 2020 at 10 hospitals across five countries in Southeast Asia, including Indonesia and the Philippines. 

It found that most infections were caused by bacteria unlikely to respond to the currently applied WHO recommended treatments. These were developed using data from high-income countries, instead of using localised data which could be more accurate and therefore effective. 

“Our study highlights the causes of serious infections in babies in countries across Southeast Asia with high rates of neonatal sepsis, and reveals an alarming burden of AMR that renders many currently available therapies ineffective for newborns,” said senior author Associate Professor Phoebe Williams, a Senior Lecturer and NHMRC Fellow in the Sydney School of Public Health.

“Guidelines must be updated to reflect local bacterial profiles and known resistance patterns. Otherwise, mortality rates are only going to keep climbing.”

The problem is further compounded by a lack of new antimicrobial medications in development for infants and babies, added co-author Michelle Harrison, PhD candidate and Project Coordinator of NeoSEAP in the Sydney School of Public Health. 

“It takes about 10 years for a new antibiotic to be trialled and approved for babies,” Harrison said.

“With so few new drug candidates in the first place, we need a significant investment in antibiotic development.”

Gram-negative bacteria responsible for 80% of infections

For the samples which tested positive for fungal or bacterial infections, the team analysed whether they were caused by gram-positive or gram-negative bacteria – referring to the structure of the bacteria’s cell wall which influences how likely it is to develop and acquire antibiotic resistance. 

Gram-negative bacteria like E. coli, Klebsiella and Acinetobacter were responsible for nearly 80% of infections and are more likely to develop (and spread) antibiotic resistance.

“These bugs have long been considered to only cause infections in older babies, but are now infecting babies in their first days of life,” said Associate Professor Williams. 

When treating babies, doctors don’t have time to wait for lab tests to confirm the exact cause of the infection, and often make an educated guess from published data, most often based on high-income populations, to guide treatment. These tests are also frequently delayed or falsely negative due to the difficulty of collecting blood samples.

Harrison explained that the findings showcase the importance of locally relevant data to guide routine medical decision-making.

“We need more region-specific surveillance to guide treatment decisions. Otherwise, we risk reversing decades of progress in reducing child mortality rates,” she said.

“Our results also revealed fungal infections caused nearly one in 10 serious infections in babies – a much higher rate than in high-income countries. 

“We need to ensure doctors are prescribing treatments that have the best chance at saving a baby’s life.”

Source: University of Australia

Categories : Antibiotics Diet and NutritionTags :

Study Finds Caffeine Can Weaken Effectiveness of Certain Antibiotics

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Photo by Mike Kenneally on Unsplash

Ingredients of our daily diet – including caffeine – can influence the resistance of bacteria to antibiotics. This has been shown in a new study by a team of researchers at the Universities of Tübingen and Würzburg led by Professor Ana Rita Brochado. They discovered bacteria such as Escherichia coli (E. coli) orchestrate complex regulatory cascades to react to chemical stimuli from their direct environment which can influence the effectiveness of antimicrobial drugs such as ciprofloxacin.

In a systematic screening, Brochado’s team investigated how 94 different substances – including antibiotics, prescription drugs, and food ingredients – influence the expression of key gene regulators and transport proteins of the bacterium E. coli, a potential pathogen. Transport proteins function as pores and pumps in the bacterial envelope and control which substances enter or leave the cell. A finely tuned balance of these mechanisms is crucial for the survival of bacteria.

Researchers describe phenomenon as an ‘antagonistic interaction’

“Our data show that several substances can subtly but systematically influence gene regulation in bacteria,” says PhD student Christoph Binsfeld, first author of the study. The findings suggest even everyday substances without a direct antimicrobial effect – eg, caffeinated drinks – can impact certain gene regulators that control transport proteins, thereby changing what enters and leaves the bacterium. “Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli – which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” explains Ana Rita Brochado. This results in caffeine weakening the effect of this antibiotic. The researchers describe this phenomenon as an ‘antagonistic interaction.’

“Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli – which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” says Prof Brochado.

This weakening effect of certain antibiotics was not detectable in Salmonella enterica, a pathogen closely related to E. coli. This shows that even in similar bacterial species, the same environmental stimuli can lead to different reactions – possibly due to differences in transport pathways or their contribution to antibiotic uptake.

The study, which has been published in the scientific journal PLOS Biology, makes an important contribution to the understanding of what is called ‘low-level’ antibiotic resistance, which is not due to classic resistance genes, but to regulation and environmental adaptation. This could have implications for future therapeutic approaches, including what is taken during treatment and in what amount, and whether another drug or food ingredient – should be given greater consideration.

Source: University of Tübingen

Categories : AntibioticsTags :

New Antibiotic to Fight C. Diff Proves Effective in Clinical Trial

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Clostridioides difficile. Credit: CDC

As the effectiveness of antibiotics meant to fight the deadly superbug Clostridioides difficile wanes, a research team at the University of Houston is seeing positive results of a new antibiotic on the scene – ibezapolstat – which is proving successful in fighting these infectious bacteria in clinical trials.

C. diff is a leading cause of death from gastroenteritis, causing gastrointestinal illness ranging from diarrhoea and abdominal pain to toxic megacolon, sepsis and death.

Until now the frontline treatments for C. diff have been the antibiotics vancomycin, with a sustained clinical cure of 42% to 71%, and fidaxomicin at 67%.

And yet, a superbug would not be so deadly if it was not able to outlive the very medicines meant to destroy it.

“Both vanco and fidaxo are associated with emerging antimicrobial resistance. C. difficile infection recurrence is associated with increased mortality, decreased quality of life and higher healthcare costs. New antibiotics are urgently needed,” said Kevin Garey, Professor of Drug Discovery at the University of Houston College of Pharmacy and senior author on recent clinical trial results with ibezapolstat published in Lancet Microbe.

C. diff infections often return when the natural balance in the gut stays disrupted – good bacteria like Bacillota, Bacteroidota, and Actinomycetota are reduced, while harmful types like Pseudomonadota increase. These changes can weaken the gut’s defences, causing a loss of the kind of bacteria that helps break down bile acids. When that happens, harmful bacteria can easily take over.

“Ibezapolstat’s mechanism of action helps restore the healthy microbiota that causes C. diff recurrence” said study lead author Taryn A. Eubank, research assistant professor of Pharmacy Practice and Translational Research at UH.

Enter ibezapolstat

Ibezapolstat has a way of working that kills harmful C. difficile bacteria without harming the good bacteria in the gut that protect against C. diff infections.

“A randomized, double-blind, active-controlled study showed high rates of initial clinical cure in participants treated with ibezapolstat, with no recurrence,” reports Garey.

“Ibezapolstat was found to be safe, well tolerated, and was associated with the preservation of key health-promoting bacteria responsible for bile acid homoeostasis, a key component in preventing recurrent C. difficile infection.”

Eubank added, “This helps confirm the important anti-C diff recurrence properties of Ibezapolstat.”

Ibezapolstat is being developed by Acurx Pharmaceuticals progressing towards phase III clinical trials. The study was conducted at 15 centres, primarily outpatient clinics and hospitals in the United States. Participants were aged 18–90 years, with diarrhoea and a confirmed diagnosis of mild or moderate C. difficile infection.

“The findings of our study support further clinical development of ibezapolstat into phase III clinical trials and eventual use in our patients,” said Garey.

Source: University of Houston