Year: 2022

Categories : Diseases, Syndromes and Conditions PaediatricsTags :

Azithromycin in Infant RSV Does Not Prevent Wheezing, May be Harmful

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Photo by William-Fortunato on Pexels

A recent study on the impact of the antibiotic azithromycin during severe respiratory syncytial virus (RSV) bronchiolitis overwhelmingly supports current bronchiolitis guidelines in the US, which recommend against antibiotics during acute bronchiolitis.

The anti-inflammatory properties of azithromycin can be beneficial in some chronic lung diseases, such as cystic fibrosis. With that in mind, researchers investigated its potential to prevent future recurrent wheezing among infants hospitalised with RSV. With such babies at increased risk of developing asthma later in childhood, the scientists hoped to find a therapy to reduce this risk.

The study, published in NEJM Evidence, also provided considerable evidence that severe RSV bronchiolitis in early life increases the likelihood of repeated wheezing episodes in early childhood, often leading to asthma.

“The major message is that antibiotics don’t have a role, either in the management of acute RSV bronchiolitis or to reduce subsequent wheezing,” said co-corresponding author Leonard Bacharier, MD, professor of Pediatrics at Monroe Carell Jr Children’s Hospital at Vanderbilt. “As a matter of fact, we found that antibiotics in general in our study of severe RSV bronchiolitis increased the risk of subsequent recurrent wheezing over the following two to four years.”

“We need to discourage the use of this therapy, as it is potentially harmful,” he said.

The study examined children hospitalised with RSV bronchiolitis during a single-center, double-blind, placebo-controlled trial.

An earlier pilot trial enrolled 40 infants hospitalised with RSV bronchiolitis where treatment with azithromycin, and this showed a reduction in the likelihood of recurrent wheeze over the following year.

In the current study, 200 otherwise healthy 1- to 18-month-old children who were hospitalised for RSV bronchiolitis were prospectively randomised to either oral azithromycin or a placebo for 14 days. The group was broadly representative of the population of children who experience severe RSV bronchiolitis.

Antibiotics are sometimes used in the treatment of RSV because co-occurring complications lead medical teams to prescribe them, thinking there is a bacterial component to the illness, Prof Bacharier said.
“This condition can be managed by supportive care – oxygen, fluids, observation, time and love,” he stressed. “If a clinician is going to use an antibiotic in the setting of RSV bronchiolitis, there needs to be a very strong rationale for doing so. There is substantial evidence to suggest that children who receive antibiotics early in life are at an increased risk of developing asthma, and this study is consistent with that evidence.”

Source: EurekAlert!

Categories : COVID Metabolic DisordersTags : 1 Comment

COVID Infection not Associated With Increased New-onset Diabetes Risk

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Source: Fusion Medical Animation on Unsplash

Using in vitro modelling the SARS-CoV-2 infection of human pancreatic cells, researchers have found that COVID infection is likely not associated with an increased new-onset diabetes risk. At the same time, another study has suggested that in hospitalised COVID patients, it may be a temporary form of the disease resulting from the acute stress of viral infection.

The findings, which are to appear in Cell Reports, address concerns raised over the past 18 months that infection with SARS-CoV-2 may trigger new-onset diabetes.  However, the supporting evidence for this has remained sparse, with at times conflicting evidence impeding with a proper risk assessment.

The team of researchers at the Icahn School of Medicine at Mount Sinai demonstrated that SARS-CoV-2 targets virtually all types of pancreatic cells, not just the insulin-producing beta cells, using the ACE2 receptor to gain access. However, the infection in the pancreas remained highly circumscribed, largely non-cytopathic and despite high viral burden in infected subsets, promoted only modest cellular perturbations and inflammatory responses.

Similar experimental outcomes were also observed after in vitro infection with endemic coronaviruses not previously associated with diabetes. Taken together, these findings challenge the notion that direct beta cell infection and destruction by SARS-CoV-2 can precipitate diabetes onset.

“Our provisional conclusions indicate that SARS-CoV-2 infection is likely not associated with an increased risk for new-onset diabetes,” said study leader Dirk Homann, MD, Professor of Medicine at Icahn Mount Sinai. “However, a history of SARS-CoV-2 infection may yet promote prolonged glycometabolic perturbations and even an increase in cumulative diabetes risk in vulnerable populations. Over the next few years, we need to pay careful attention to emerging observational and retrospective studies that determine diabetes incidence rates of previously SARS-CoV-2-infected individuals.”

To evaluate permissiveness of human pancreatic islet cells to in vitro SARS-CoV-2 infection, the team of researchers employed an in vitro infection model of primary human pancreatic islets with SARS-CoV-2 as well as endemic human coronaviruses. The team precisely delineated pancreatic infection patterns and associated cellular changes at the single-cell level. Altogether, they found that the extent and consequences of pancreatic SARS-CoV-2 infection, even under in vitro conditions of enhanced virus exposure, remained decidedly limited.

“Concerns surrounding the possibility that infection with SARS-CoV-2, the etiological agent of COVID, may cause new-onset diabetes persist amidst an evolving research landscape,” said Verena van der Heide, MD, PhD, co-first author of the study and postdoctoral research fellow at the Icahn School of Medicine at Mount Sinai. “Our findings stand in notable contrast to three recent reports that also based their speculation about the diabetogenic potential of SARS-CoV-2 on in vitro infection of human islets. As detailed in our manuscript, however, we believe that our careful experimental design and comprehensive analysis strategy make a compelling case for the considerable limits of pancreatic SARS-CoV-2 infection.”

“There are strong epidemiological associations between COVID infection in humans and diabetes, but whether the SARS-CoV-2 virus actually infects and damages the insulin-producing cells in the human pancreas, the so-called ‘beta cells,’ has been highly controversial,” said Andrew Stewart, MD, Director of the Diabetes, Obesity and Metabolism Institute at Icahn Mount Sinai. “This study by Dr. Homann and his collaborators in Mount Sinai’s Precision Immunology Institute and the Department of Microbiology provides strong evidence that SARS-CoV-2 causes little or no damage to beta cells, making it unlikely that COVID infection can predispose to development of Type 1 diabetes.”    

The conclusions they came to are in line with a 2020 report by Dr Homann and his team, showing that ACE2 receptors and other entry factors are lacking among islet endocrine cells but readily detected in microvascular and ductal structures of the pancreas.

Meanwhile, a second, separate study of 594 individuals who exhibited signs of diabetes mellitus during the early pandemic showed that half of the 79 patients without a diabetes diagnosis reverted to normal blood sugar levels by one year.

“We believe that the inflammatory stress caused by COVID may be a leading contributor to ‘new-onset’ or newly diagnosed diabetes,” said Sara Cromer, MD, lead author of the second study. “Instead of directly causing diabetes, COVID may push patients with pre-existing but undiagnosed diabetes to see a physician for the first time, where their blood sugar disorder can be clinically diagnosed. Our study showed these individuals had higher inflammatory markers and more frequently required admission to hospital ICUs than COVID patients with pre-existing diabetes.”

The second study was published in the Journal of Diabetes and its Complications.

Source: Mount Sinai Medical Center

Categories : Medical Research & TechnologyTags :

X-Ray Images With Vastly Lower Radiation Doses

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A new scintillation material developed by KAUST scientists can bring significant improvements to X-ray imaging in medicine, industry and security. Credit: KAUST

Scientists have successfully produced an exceptionally efficient, robust and flexible scintillation film to bring significant improvements in X-ray imaging, enabling much lower radiation doses to be used.

Scintillation materials release visible light, or “scintillate,” in response to absorbing  high-energy X-ray photons, enabling an image to be captured.

Researchers are continually exploring ways to make scintillation technology more sensitive, efficient and readily adaptable. The researchers, led by  Omar F Mohammed, Associate Professor of Chemical Sciences at King Abdullah University of Science and Technology (KAUST), sought to come up with an improved scintillation screen.

“Currently used materials suffer from several drawbacks, including complex and high-cost fabrication processes, radioluminescence afterglow and nontunable scintillation,” said Yang Zhou, a postdoc in Prof Mohammed’s lab.

Materials called lead halide perovskites have attracted considerable attention and shown significant promise. Novel perovskites are a category of materials that share the same crystal structure as the natural perovskite mineral calcium titanium oxide, but they include a variety of different atoms that replace all or some of those found in natural perovskite. 
To avoid toxicity problems and reduce cost, the researchers explored the use of elements besides lead. The newly developed screens are described in ACS Energy Letters.

The flexible scintillation screens the team developed can detect X-rays at ultralow levels, “approximately 113 times lower than a typical standard dose for X-ray medical imaging,” said Omar Mohammed, leader of the research group.

“Another vital advance is that the X-ray spatial resolution reported in this study is the highest achieved to date for powder-based screens,” said Dr Zhou.

“The physical flexibility of our films is also very important,” added Prof Mohammed. He explains that highly efficient flexible scintillation screens are urgently needed for using X-rays to better analyse awkward shapes.

The team plans to commercialise their advance, and to hope to refine their fabrication techniques.

Source: EurekAlert!

Categories : Diseases, Syndromes and Conditions Medical Research & TechnologyTags :

Sanofi’s Rare Disease Database Aids Healthcare Practitioners

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Image source: CDC/Unsplash

Sanofi’s rare disease database that helps healthcare practitioners tackle their unique challenges – and knowing that treatments are available directly improves patients’ wellbeing. This comprehensive database has also aided rare disease research.

Johannesburg, 28 February 2022: Patients with rare diseases present unique challenges to healthcare practitioners (HCPs). Obstacles to caring for them include diagnostic delays and a lack of information, expertise, and treatment options for many rare diseases. HCPs play a vital role in enhancing the quality of life for patients and families living with a rare disease by making appropriate referrals to specialists, helping to coordinate care, and assisting patients in obtaining the proper support.1,2

A disease is defined as ‘rare’ when it affects fewer than 1 in 2000 people.3

Over 7000 rare diseases have been described to date, affecting over 350 million people worldwide.3,4 While most (70-80%) of rare diseases are genetic and inherited, some may be acquired, and 70% are exclusively paediatric in onset.5

Recent surveys showed that those living with rare diseases had a significantly higher prevalence of anxiety and depression compared to the general population.5,6 Levels of high stress can become even worse for carers when the person they are supporting has a diagnosis with no available treatment option.5,6

Monique Nel, Medical Advisor – Rare Diseases at Sanofi says: “Sanofi has been dedicated to researching and developing innovative treatments for rare diseases for 40 years. Currently, Sanofi has one of the largest rare diseases pipelines in the industry, across multiple diseases and modalities.7”

“Our rare disease patient registries have grown to represent one of the largest collections of real-world data for rare diseases collected over the past 30 years. We have a presence in 68 countries worldwide, with more than 920 participating sites and more than 17 800 patients enrolled.”

These registries have helped researchers to publish studies describing the underlying biology of disease, identify risk factors impacting treatment outcomes, and share guidelines for monitoring and treatment.

A further useful resource for HCPs and patients is the list of rare diseases maintained by the Genetic and Rare Diseases Information Center (GARD) of the US National Institutes of Health.8          

Says Nel: “We understand the difficulty that healthcare professionals face when it comes to patient diagnosis of a rare disease, and that a coordinated approach to diagnosis and care for people living with rare diseases is needed. Rare diseases deserve the same amount of time, resources and dedication to finding effective treatments and therapies as any other conditions, which is a mission that Sanofi strives to promote every day, to help HCPs to improve diagnosis.”

References:

  1. Elliott E, Zurynski Y. Rare diseases are a ‘common’ problem for clinicians. Aust Fam Physician. 2015 Sep;44(9):630. http://www.ncbi.nlm.nih.gov/pubmed/26488039
  2. Dudding-Byth T. A powerful team: the family physician advocating for patients with a rare disease. Aust Fam Physician. 2015 Sep;44(9):634. http://www.ncbi.nlm.nih.gov/pubmed/264880401. NIH.
  3. Genetic and Rare Disease Information Center. FAQs About Rare Diseases. Available at: https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases
  4. Bogart KR, Irvin VL. Health-related quality of life among adults with diverse rare disorders. Orphanet J Rare Dis. 2017 Dec 7;12(1):177. doi: 10.1186/s13023-017-0730-1. PMID: 29212508; PMCID: PMC5719717.
  5. Nguengang Wakap S, Lambert DM, Olry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet 2020;28:165–173. https://doi.org/10.1038/s41431-019-0508-0
  6. National Alliance for Caregiving. Rare Disease Caregiving in America. Available at: https://www.caregiving.org/wp-content/uploads/2020/05/NAC-RareDiseaseReport_February-2018_WEB.pdf
  7. Sanofi Your Health webpage. Rare Disease. https://www.sanofi.com/en/your-health/specialty-care/rare-diseases
  8. National Institutes of Health, Genetic and Rare Diseases Information Center. Caring for your patient with a rare disease.  Available at: https://rarediseases.info.nih.gov/guides/pages/122/caring-for-your-patient-with-a-rare-disease
Categories : Lab Tests and ImagingTags :

New Biosensor Rapidly Measures ATP and Lactate in Blood Samples

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The prototype of the ATP and lactate sensor developed in the study (left); and the integrated sensor chip that detects ATP and lactate levels (right). Credit: Akihiko Ishida, Hokkaido University

Scientists at Hokkaido University have developed a prototype sensor that could help doctors rapidly measures levels of adenosine triphosphate (ATP) and lactate in blood samples from patients, aiding in the rapid assessment of the severity of conditions such as sepsis.

The scientists detailed their prototype biosensor in the journal Biosensors and Bioelectronics.

ATP is a molecule found in every living cell that stores and carries energy. In red blood cells, ATP is produced by a biochemical pathway called the Embden–Meyerhof pathway. Severe illnesses such as multiple organ failure, sepsis and influenza reduce the amounts of ATP produced by red blood cells.

As such, the severity of these illnesses could be gauged by monitoring the amounts of ATP and lactates in a patient’s blood. “In 2013, our co-authors at Tokushima University proposed the ATP-lactate energy risk score (A-LES) for measuring ATP and lactate blood levels to assess acute influenza severity in patients,” explained Akihiko Ishida, an applied chemist at Hokkaido University. “However, current methods to measure these levels and other approaches for measuring disease severity can be cumbersome, lengthy or not sensitive enough. We wanted to develop a rapid, sensitive test to help doctors better triage their patients.”

The researchers developed a biosensor that can detect levels of ATP and lactate in blood with great high sensitivity in as little as five minutes. The process is straightforward. Chemicals are added to a blood sample to extract ATP from red blood cells. Enzymes and substrates are then added to convert ATP and lactate to the same product that can be detected by specially modified electrodes on a sensor chip; the amount of by-product present in the sample increases the electrical current measured.

Schematic representation of the proposed sensor for sequentially detecting ATP and lactate levels in the blood. Through a series of chemical reactions, ATP and lactate are converted to hydrogen peroxide, the breakdown of which to water H2O causes the sensor chip to generate a signal that is detected by the sensor.

The team conducted parallel tests and found that other components present in blood, such as ascorbic acid, pyruvic acid, adenosine diphosphate (ADP), urate and potassium ions, don’t interfere with the ability of the electrodes to accurately detect ATP and lactate. They also compared their sensor with those currently available and found it allowed for the relatively simple and rapid measurement of the two molecules.

“We hope our sensor will enable disease severity monitoring and serve as a tool for diagnosing and treating patients admitted to intensive care units,” said Ishida.

The researchers plan to further simplify the measurement process by integrating an ATP extraction method into the chip itself, as well as reducing the size of the sensor system.

Source: Hokkaido University

Categories : HospitalsTags : 1 Comment

Hospitals in Ukraine Face Oxygen Shortage, MSF Suspends Operations

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Supplies of medical oxygen in Ukraine are dangerously low due to disruption caused by the Russian invasion, the World Health Organization has warned.

Due to the crisis, the WHO estimates that the country needs an additional 20–25% increase in oxygen supplies over and above its normal needs. As it currently stands, the transport of oxygen cylinders across the country is being disrupted, especially into the capital Kyiv. As of 27 February, many hospitals across the country, including in Kyiv, had less than 24 hours’ supply remaining.

Furthermore, oxygen production facilities are experiencing shortages of zeolite, which is needed for the safe production of oxygen in the pressure swing absorption process. 

Prior to the conflict, the WHO had worked with Ukraine to improve its oxygen supply infrastructure, especially during the COVID pandemic. “Of the over 600 health facilities nationwide assessed by WHO during the pandemic, close to half were directly supported with supplies, technical know-how and infrastructure investments, enabling health authorities to save tens of thousands of lives,” the WHO said. This progress is threatening to be undone.

“Compounding the risk to patients, critical hospital services are also being jeopardised by electricity and power shortages, and ambulances transporting patients are in danger of getting caught in the crossfire,” the WHO said in its press release.

To offset this, the WHO is working through regional networks to bring in oxygen, as well as providing trauma treatment supplies. These would be brought in through a safe logistics corridor in Poland.

Médecins Sans Frontières (MSF) has announced that it is suspending activities in Ukraine. “These included care for people living with HIV in Severodonetsk; care for patients with tuberculosis in Zhytomyr; and improving access to healthcare access in Donetsk, in eastern Ukraine, where we have been providing much-needed healthcare, including for mental health, to conflict-affected communities,” the organisation said in an announcement.

However, it is working to ensure some continuity of its operations, and are working to provide trauma training to certain hospitals and have provided some trauma supplies.

The Ukrainian capital of Kyiv has also put out a call for donations of medicines, such as the antiviral amixin, the antibiotic nifuroxazide and the haemostatic agent aminocaproic acid.

Source: World Health Organization

Categories : Cancer Expert OpinionTags :

To Properly Use AI to Analyse Breast Cancers, Look to Past Mistakes

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Source: National Cancer Institute

Doctors writing in an editorial in JAMA Health Forum caution that while using AI to analyse breast cancer tumours has the potential to improve healthcare efficiency and outcomes, similar technological leaps have previously led to higher rates of false-positive tests and over-treatment.

The editorial wasco-written by Joann G. Elmore, MD, MPH, professor of medicine at the David Geffen School of Medicine at UCLA, and Christoph I. Lee, MD, MS, MBA, a professor of radiology at the University of Washington School of Medicine.

“Without a more robust approach to the evaluation and implementation of AI, given the unabated adoption of emergent technology in clinical practice, we are failing to learn from our past mistakes in mammography,” the authors wrote.

One of those “past mistakes in mammography,” the authors said, was adjunct computer-aided detection (CAD) tools, which grew rapidly in popularity in the field of breast cancer screening starting more than two decades ago. CAD was approved by the FDA in 1998, and by 2016 more than 92% of U.S. imaging facilities were using the technology to interpret mammograms and hunt for tumours. However, CAD did not improve mammography accuracy., according to the evidence. “CAD tools are associated with increased false positive rates, leading to overdiagnosis of ductal carcinoma in situ and unnecessary diagnostic testing,” the authors wrote. The US Medicare system stopped paying for CAD in 2018, but by then the tools had run up more than $400 million a year in wasted health costs.

“The premature adoption of CAD is a premonitory symptom of the wholehearted embrace of emergent technologies prior to fully understanding their impact on patient outcomes,” Drs Elmore and Lee wrote. “As AI algorithms are increasingly receiving FDA clearance and becoming commercially available with ROC curves similar to what we observed prior to CAD clearance and adoption, how can we prevent history from repeating itself?”

The doctors suggest a number of safeguards to avoid “repeating past mistakes” such as tying reimbursement to proven efficacy.

Source: UCLA Health

Categories : Respiratory DiseasesTags :

Nintedanib Slows Autoimmune-related Lung Disease

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Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

Findings from a new clinical trial published in Arthritis & Rheumatology reveal that nintedanib,  an intracellular inhibitor of tyrosine kinases, may help patients with fibrosing from autoimmune disease-related interstitial lung diseases (ILDs).

ILDs are a common manifestation of systemic autoimmune diseases such as rheumatoid arthritis. Connective tissue diseases and vasculitides affect all areas of the lungs (bronchioles, parenchyma, alveoles) which is why ILD is a common feature of rheumatology diseases.

The trial enrolled 170 subjects with a fibrosing ILD other than idiopathic pulmonary fibrosis, with diffuse fibrosing lung disease of > 10% extent on high-resolution CT imagery, forced vital capacity (FVC) ≥ 45% predicted and diffusing capacity of the lungs for carbon monoxide ≥ 30% –< 80% predicted. FVC is a predictor of mortality in patients with autoimmune disease-associated ILDs.

Patients were randomised to receive nintedanib or placebo. Investigators assessed patients’ forced vital capacity (FVC). The trial found that the rate of decline in FVC over one year was -75.9 mL/year with nintedanib versus -178.6 mL/year with placebo.

“Until now, therapies that can significantly reduce the rate of decline in lung function in connective tissue disease–related ILDs characterised by progressive fibrosis have been lacking. We now have a therapeutic approach that offers a strategy for reducing the morbidity associated with these diseases,” said lead author Eric L. Matteson, MD, MPH, of the Mayo Clinic College of Medicine and Science.

Source: Wiley

Categories : Medical IndustryTags :

A Synthetic Alternative to Pig-derived Heparin

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Photo by Corinna Widmer from Pexels

Scientists have developed a process to synthesise the vital blood thinner heparin, which is normally harvested from pig intestines. This synthetic heparin would help the quality control issues and shortages associated with pig-derived heparin.

The most expensive part of a pig is not a cut of bacon or a chop, but the part of the intestine used to make heparin. About 2000 pigs required to produce a kilogram of heparin, which provides medication to up to 6000 patients. In total, it is estimated that about one billion primarily Chinese food pigs each year also supply intestines for the extraction and processing of heparin.

However, this can cause problems for patients. When making medicines derived from animals, the chemical structure is rarely uniform. There are relatively common but harmless side effects, and in very rare cases severe and life-threatening immune reactions. Additionally, there are ethical and religious concerns for many patients. Bovine- and sheep-derived heparin are also produced but have the same concerns of being of animal origin. In fact, prior to 2000, heparin was derived from cows until the outbreak of mad cow disease.

Therefore, it has long been an ambition among researchers to make heparin in a laboratory to get cleaner heparin without side effects. Now researchers from the Copenhagen Center for Glycomics at the University of Copenhagen are ready with a study that shows that it is possible to make heparin without the use of animals.  which was published in Science Advances.

“By making heparin without the animal, you get a much cleaner and more uniform chemical structure. We show that we can do it in the laboratory, i.e. in a so-called ‘cell factory’, in the same way as many other types of medicine are made. It is a step in the direction of the development that has also happened with insulin, which was previously extracted from the pancreas in pigs before we learned to produce it in the laboratory,” explained Associate Professor Rebecca Miller, who led the study. 

There is already a synthetic alternative to heparin, but it is difficult to dose and can lead to overdose. Because of this, GPs often prescribe pig-derived heparin to their patients.

Heparin is today extracted from pig intestines’ mucosa. Due to the sheer number of patients who need the medicine, the scale of the production is vast, making quality control a recurring problem for manufacturers.

In 2008, a number of stocks of heparin from Chinese pigs were recalled when it was found that the medicine was contaminated. The case ended up costing the lives of more than 100 Americans.

“Of course you want to avoid that, in addition to moving the source from animals to laboratory cells. With our new technology, we have made a design for how to make heparin in a cell that is clean and uniform and it suggests that it has the same medicinal effect as market heparin. In this way, you potentially get a product that leads to neither common nor life-threatening side effects,” said Richard Karlsson, PhD, who has also contributed to the main author of the study.

Right now, the world is facing a shortage of heparin because swine flu has thinned the pig population in China, the largest heparin producer.
Next steps would be to scale up production to provide much larger quantities of the new synthetic heparin. 

Source: University of Copenhagen

Categories : Diseases, Syndromes and ConditionsTags :

Study Reveals the Intricacy of C. Diff’s Armour

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The spectacular structure of the protective armour of superbug C. difficile has been revealed for the first time showing the close-knit yet flexible outer layer – like chain mail. This assembly prevents molecules getting in and provides a new target for future treatments, according to the scientists at Newcastle, Sheffield and Glasgow Universities who have uncovered it. Credit: Newcastle University, UK

The spectacular structure of the protective armour of C. difficile has been revealed for the first time showing the close-knit yet flexible outer layer – like a mediaeval knight’s chain mail.

This tight arrangement keeps molecules from getting in and provides a new target for future treatments, according to the scientists who have uncovered it.

Published in Nature Communications, the team of scientists outlined the structure of the main protein, SlpA, that forms the links of the chain mail and how they link up to form a pattern and create this flexible armour.
One of the many ways that Clostridioides difficile has to protect itself from antibiotics is a special layer that covers the cell of the whole bacteria – the surface layer or S-layer. This flexible armour protects against the entry of drugs or molecules released by our immune system to fight bacteria.

Using a combination of X-ray and electron crystallography, the team determined the structure of the proteins and their arrangement.

Corresponding author and lead researcher Dr Paula Salgado said: “I started working on this structure more than 10 years ago, it’s been a long, hard journey but we got some really exciting results! Surprisingly, we found that the protein forming the outer layer, SlpA, packs very tightly, with very narrow openings that allow very few molecules to enter the cells. S-layer from other bacteria studied so far tend to have wider gaps, allowing bigger molecules to penetrate. This may explain the success of C.diff at defending itself against the antibiotics and immune system molecules sent to attack it.

“Excitingly, it also opens the possibility of developing drugs that target the interactions that make up the chain mail. If we break these, we can create holes that allow drugs and immune system molecules to enter the cell and kill it.”

Antimicrobial resistance (AMR), a growing problem, was declared by WHO as one of the top 10 global public health threats facing humanity.
One of the many bacteria that have evolved resistance to antibiotics, C. diff infects the human gut and is resistant to all but three current drugs. Antibiotics only compound the problem, as the good bacteria in the gut are killed alongside those causing an infection and, as C. diff is resistant, it can grow and cause diseases ranging from diarrhoea to death due to massive lesions in the gut. Since the only way to treat C.diff is to take antibiotics, it creates a vicious cycle of recurrent infections.

This knowledge could lead to the development of C. diff specific drugs that break the protective layer, creating holes to allow drug molecules to penetrate and kill the cell.

Dr Rob Fagan, who helped carry out the electron crystallography work, said: “We’re now looking at how our findings could be used to find new ways to treat C. diff infections such as using bacteriophages to attach to and kill C. diff cells – a promising potential alternative to traditional antibiotic drugs.”

Source: EurekAlert!