Tag Archives: Biotechnology

A New Treatment for Lung Infections: Scientists Have Created a Unique “Living Medicine”

Scientists have created the first “living medicine” to cure lung infections. This innovative treatment is aimed at Pseudomonas aeruginosa, a bacteria known for its resistance to many antibiotics and a frequent cause of infections in hospitals.

This treatment involves the use of a modified form of the Mycoplasma pneumoniae bacterium, which has had its disease-causing abilities removed and reprogrammed to target P. aeruginosa. The modified bacterium is used in conjunction with low doses of antibiotics that would not be effective on their own.

Researchers tested the efficacy of the treatment in mice, finding that it significantly reduced lung infections. The “living medicine” doubled mouse survival rate compared to not using any treatment. Administering a single, high dose of the treatment showed no signs of toxicity in the lungs. Once the treatment had finished its course, the innate immune system cleared the modified bacteria in a period of four days.

The findings are published in the journal Nature Biotechnology and were funded by the “la Caixa” Foundation through the CaixaResearch Health call. The study was led by researchers at the Centre for Genomic Regulation (CRG) and Pulmobiotics in collaboration with the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona and the Institute of Agrobiotechnology (IdAB), a joint research institute of Spain’s CSIC and the government of Navarre.

P. aeruginosa infections are difficult to treat because the bacteria live in communities that form biofilms. Biofilms can attach themselves to various surfaces in the body, forming impenetrable structures that escape the reach of antibiotics.

P. aeruginosa biofilms can grow on the surface of endotracheal tubes used by critically-ill patients who require mechanical ventilators to breathe. This causes ventilator-associated pneumonia (VAP), a condition that affects one in four (9-27%) patients who require intubation. The incidence exceeds 50% for patients intubated because of severe Covid-19. VAP can extend the duration in the intensive care unit for up to thirteen days and kills up to one in eight patients (9-13%).

The authors of the study engineered M. pneumoniae to dissolve biofilms by equipping it with the ability to produce various molecules including pyocins, toxins naturally produced by bacteria to kill or inhibit the growth Pseudomonas bacterial strains. To test its efficacy, they collected P. aeruginosa biofilms from the endotracheal tubes of patients in intensive care units. They found the treatment penetrated the barrier and successfully dissolved the biofilms.

“We have developed a battering ram that lays siege to antibiotic-resistant bacteria. The treatment punches holes in their cell walls, providing crucial entry points for antibiotics to invade and clear infections at their source. We believe this is a promising new strategy to address the leading cause of mortality in hospitals,” says Dr. María Lluch, Chief Scientific Officer at Pulmobiotics, co-corresponding author of the study and principal investigator at the International University of Catalonia.

With the aim of using “living medicine” to treat VAP, the researchers will carry out further tests before reaching the clinical trial phase. The treatment is expected to be administered using a nebulizer, a device that turns liquid medicine into a mist which is then inhaled through a mouthpiece or a mask.

M. pneumoniae is one of the smallest known species of bacteria. Dr. Luis Serrano, Director of the CRG, first had the idea to modify the bacteria and use it as a ‘living medicine’ two decades ago. Dr. Serrano is a specialist in synthetic biology, a field that involves repurposing organisms and engineering them to have new, useful abilities. With just 684 genes and no cell wall, the relative simplicity of M. pneumoniae makes it ideal for engineering biology for specific applications.

One of the advantages of using M. pneumoniae to treat respiratory diseases is that it is naturally adapted to lung tissue. After administering the modified bacterium, it travels straight to the source of a respiratory infection, where it sets up shop like a temporary factory and produces a variety of therapeutic molecules.

By showing that M. pneumoniae can tackle infections in the lung, the study opens the door for researchers to create new strains of the bacteria to tackle other types of respiratory diseases such as lung cancer or asthma. “The bacterium can be modified with a variety of different payloads – whether these are cytokines, nanobodies, or defensins. The aim is to diversify the modified bacterium’s arsenal and unlock its full potential in treating a variety of complex diseases,” says ICREA Research Professor Dr. Luis Serrano.

In addition to designing the ‘living medicine’, Dr. Serrano’s research team is also using their expertise in synthetic biology to design new proteins that can be delivered by M. pneumoniae. The team is using these proteins to target inflammation caused by P. aeruginosa infections.

Though inflammation is the body’s natural response to an infection, excessive or prolonged inflammation can damage lung tissue. The inflammatory response is orchestrated by the immune system, which releases mediator proteins such as cytokines. One type of cytokine – IL-10 – has well-known anti-inflammatory properties and is of growing therapeutic interest.

Research published in the journal Molecular Systems Biology by Dr. Serrano’s research group used protein-design softwares ModelX and FoldX to engineer new versions of IL-10 purposefully optimized to treat inflammation. The cytokines were designed to be created more efficiently and to have a higher affinity, meaning less cytokines are needed to have the same effect.

The researchers engineered strains of M. pneumoniae that expressed the new cytokines and tested its efficacy in the lungs of mice with acute P. aeruginosa infections. They found that engineered versions of IL-10 were significantly more effective at reducing inflammation compared to the wild-type IL-10 cytokine.

According to Dr. Ariadna Montero Blay, co-corresponding author of the study in Molecular Systems Biology, “live biotherapeutics such as M. pneumoniae provide ideal vehicles to help overcome the traditional limitations of cytokines and unlock their huge potential in treating a variety of human diseases. Engineering cytokines as therapeutic molecules was critical to tackle inflammation. Other lung diseases such as asthma or pulmonary fibrosis could also stand to benefit from this approach.”

Reference: “Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms” by Rocco Mazzolini, Irene Rodríguez-Arce, Laia Fernández-Barat, Carlos Piñero-Lambea, Victoria Garrido, Agustín Rebollada-Merino, Anna Motos, Antoni Torres, Maria Jesús Grilló, Luis Serrano and Maria Lluch-Senar, 19 January 2023, Nature Biotechnology.
DOI: 10.1038/s41587-022-01584-9

Beware of the Microbial Mirage: Current Microbiome Analyses May Mislead Scientists With False Species Detection

Research study of simulated microbial communities shows analyses are flawed by incomplete DNA databases.

Common approaches to analyzing DNA from a community of microbes, called a microbiome, can yield erroneous results, in large part due to the incomplete databases used to identify microbial DNA sequences. A team led by Aiese Cigliano of Sequentia Biotech SL, and Clemente Fernandez Arias and Federica Bertocchini of the Centro de Investigaciones Biologicas Margarita Salas, report these findings in a research paper published on February 8 in the open-access journal PLOS ONE.

Microbiomes have been the focus of intense research efforts in recent decades. These studies range from attempts to understand conditions such as obesity and autism by examining the human gut, to finding microbes that degrade toxic compounds or produce biofuels by studying environmental communities. The most commonly used methods for studying microbial communities rely on comparing the DNA obtained from a biological sample to sequences in genome databanks. Therefore, researchers can only identify DNA sequences that are already in the databases – a fact that may severely compromise the reliability of microbiome data in unexpected ways.

To test the consistency of current methods of microbiome analysis, researchers used computer simulations to create virtual microbiome communities that imitate real-world bacterial populations. They used standard techniques to analyze the virtual communities and compared the results with the original composition. The experiment showed that results from DNA analyses can bear little resemblance to the actual composition of the community, and that a large number of the species “detected” by the analysis are not actually present in the community.

For the first time, the study demonstrates significant flaws in the techniques currently used to identify microbial communities. The researchers conclude that there is a need for increased efforts to collect genome information from microbes and to make that information available in public databases to improve the accuracy of microbiome analysis. In the meantime, the results of microbiome studies should be interpreted with caution, especially in cases where the available genomic information from those environments is still scarce.

The authors add: “This study reveals intrinsic constraints in metagenomic analysis stemming from current database limitations and how genomic information is used. To enhance the reliability of metagenomic data, a research effort is necessary to improve both database contents and analysis methods. Meanwhile, metagenomic data should be approached with great care.”

Reference: “The virtual microbiome: A computational framework to evaluate microbiome analyses” by Belén Serrano-Antón, Francisco Rodríguez-Ventura, Pere Colomer-Vidal, Riccardo Aiese Cigliano, Clemente F. Arias and Federica Bertocchini, 8 February 2023, PLOS ONE.
DOI: 10.1371/journal.pone.0280391

Funding: FB and CFA gratefully acknowledge support by the Roechling foundation. BS was partially supported by MINECO grant MTM2017-85020-P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Efficiently Harvesting Rare Earth Elements From Wastewater Using Exotic Bacteria

Rare earth elements (REEs) are a set of 17 metallic elements that possess similar chemical properties. They earned their name due to their scarce occurrence in the Earth’s crust, typically present in concentrations ranging from 0.5 to 67 parts per million. These elements play a crucial role in modern technology, including products such as LEDs, smartphones, electric motors, wind turbines, hard drives, cameras, magnets, and energy-efficient light bulbs. As a result, the demand for REEs has seen a steady rise over the past few decades and is projected to continue increasing through 2030.

Due to their scarcity and high demand, REEs can be quite costly. For instance, a kilogram of neodymium oxide currently has a price of around €200 (~$214), while terbium oxide is even more expensive at approximately €3,800 (~$4,073) for the same amount. Currently, China holds a dominant position in the mining of REEs, with near-monopolistic control over the industry. However, a recent discovery of promising new REE deposits, estimated at over one million metric tons, was made in Kiruna, Sweden and made headlines in January 2023.

The advantages of moving from a wasteful ‘linear’ economy to a ‘circular’ economy, where all resources are recycled and reused, are obvious. So could we recycle REEs more efficiently, too?

In Frontiers in Bioengineering and Biotechnology, German scientists showed that the answer is yes: the biomass of some exotic photosynthetic cyanobacteria can efficiently absorb REEs from wastewater, for example, derived from mining, metallurgy, or the recycling of e-waste. The absorbed REEs can afterward be washed from the biomass and collected for reuse.

“Here we optimized the conditions of REE uptake by the cyanobacterial biomass, and characterized the most important chemical mechanisms for binding them. These cyanobacteria could be used in future eco-friendly processes for simultaneous REE recovery and treatment of industrial wastewater,” said Dr. Thomas Brück, a professor at the Technical University of Munich and the study’s last author.

Biosorption is a metabolically passive process for the fast, reversible binding of ions from aqueous solutions to biomass. Brück and colleagues measured the potential for biosorption of the REEs lanthanum, cerium, neodymium, and terbium by 12 strains of cyanobacteria in laboratory culture. Most of these strains had never been assessed for their biotechnological potential before. They were sampled from highly specialized habitats such as arid soils in Namibian deserts, the surface of lichens around the world, natron lakes in Chad, crevices in rocks in South Africa, or polluted brooks in Switzerland.

The authors found that an uncharacterized new species of Nostoc had the highest capacity for biosorption of ions of these four REEs from aqueous solutions, with efficiencies between 84.2 and 91.5 mg per g biomass, while Scytonema hyalinum had the lowest efficiency at 15.5 to 21.2 mg per g. Also efficient were Synechococcus elongatesDesmonostoc muscorumCalothrix brevissima, and an uncharacterized new species of Komarekiella. Biosorption was found to depend strongly on acidity: it was highest at a pH of between five and six, and decreased steadily in more acid solutions. The process was most efficient when there was no ‘competition’ for the biosorption surface on the cyanobacteria biomass from positive ions of other, non-REE metals such as zinc, lead, nickel, or aluminum.

The authors used a technique called infrared spectroscopy to determine which functional chemical groups in the biomass were mostly responsible for the biosorption of REEs.

“We found that biomass derived from cyanobacteria has excellent adsorption characteristics due to their high concentration of negatively charged sugar moieties, which carry carbonyl and carboxyl groups. These negatively charged components attract positively charged metal ions such as REEs, and support their attachment to the biomass,” said first author Michael Paper, a scientist at the Technical University of Munich.

The authors conclude that biosorption of REEs by cyanobacteria is possible even at low concentrations of the metals. The process is also fast: for example, most cerium in solution was biosorbed within five minutes of starting the reaction.

“The cyanobacteria described here can adsorb amounts of REEs corresponding to up to 10% of their dry matter. Biosorption thus presents an economically and ecologically optimized process for the circular recovery and reuse of rare earth metals from diluted industrial wastewater from the mining, electronic, and chemical-catalyst-producing sectors,” said Brück.

“This system is expected to become economically feasible in the near future, as the demand and market prices for REEs are likely to rise significantly in the coming years,” he predicted.

Reference: “Rare earths stick to rare cyanobacteria: Future potential for bioremediation and recovery of rare earth elements” by Michael Paper, Max Koch, Patrick Jung, Michael Lakatos, Tom Nilges and Thomas B. Brück, 28 February 2023, Frontiers in Bioengineering and Biotechnology.
DOI: 10.3389/fbioe.2023.1130939

The study was funded by the Bavarian State Ministry of the Environment and Consumer Protection, the Ministry of Science and Health Rhineland-Palatinate, the Federal Ministry of Education and Research, the German Research Council, and EU Horizon.

Weaponizing microbes to stave off conflicts across the globe

Microorganisms should be ‘weaponized’ to stave off conflicts across the globe, according to a team of eminent microbiologists.

The paper ‘Weaponising microbes for peace’ by Anand et al, outlines the ways in which microbes and microbial technologies can be used to tackle global and local challenges that could otherwise lead to conflict, but warns that these resources have been severely underexploited to date.

Professor Kenneth Timmis, Founding Editor of AMI journals Environmental Microbiology, Environmental Microbiology Reports and Microbial Biotechnology, says that worldwide deficits and asymmetries in basic resources and services considered to be human rights, such as drinking water, sanitation, healthy nutrition, access to basic healthcare and a clean environment, can lead to competition between peoples for limited resources, tensions, and in some cases conflicts.

There is an urgent need to reduce such deficits, to level up, and to assure provision of basic resources for all peoples. This will also remove some of the causes of conflicts. There is a wide range of powerful microbial technologies that can provide or contribute to this provision of such resources and services, but deployment of such technologies is seriously underexploited.”

Professor Kenneth Timmis, Founding Editor of AMI journals Environmental Microbiology, Environmental Microbiology Reports and Microbial Biotechnology

The paper then lists a series of ways in which microbial technologies can contribute to challenges such as food supply and security, sanitation and hygiene, healthcare, pollution, energy and heating, and mass migrations and overcrowding. For example, microbes are at the core of efforts to tackle pollution by bioremediation, replacing chemical methods of treating drinking water with metalloid conversion systems, and producing biofuels from wastes.

“There is now a desperate need for a determined effort by all relevant actors to widely deploy appropriate microbial technologies to reduce key deficits and asymmetries, particularly among the most vulnerable populations,” Professor Timmis said..

“Not only will this contribute to the improvement of humanitarian conditions and levelling up, and thereby to a reduction in tensions that may lead to conflicts, but also advance progress towards attainment of Sustainable Development Goals,” he said. .

“In this paper, we draw attention to the wide range of powerful microbial technologies that can be deployed for this purpose and how sustainability can be addressed at the same time. We must weaponise microbes for peace.”

The editorial is published in Microbial Biotechnology, an Applied Microbiology International publication, on March 7 2023.

Recommended actions to implement relevant microbial technology solutions to deficits

We need to urgently supply to communities lacking adequate levels of basic resources/services the infrastructure and know-how (capacity building), and funding for

  1. use of agrobiologics to increase crop yields, by providing green nitrogen, stimulating plant growth, and combatting pathogens and pests,

  2. exploitation of plant:microbe partnerships to improve soil health and implement regenerative agriculture,

  3. creation of nutritious fermented food from locally available crops,

  4. better use of microbes in the feed and food supply chains,

  5. production of microbial food for humans and farm animals,

  6. drinking water production and quality safeguarding,

  7. waste treatment with resource recovery,

  8. creation of modular DIY digital medical centres,

  9. production of vaccines and medicines,

  10. bioremediation and biorestoration of the environment in general and natural ecosystems in particular, to create healthier habitats and promote biodiversity

  11. reduction of greenhouse gas production and capturing carbon,

  12. production of biofuels,

  13. creation of local employment opportunities associated with the above,

  14. development of transdisciplinary approaches, using chemistry-related, computation technologies, psychology-related and other approaches that are synergistic to microbial solutions and

  15. education in societally relevant microbiology

Journal reference:

Anand, A., et al. (2023) Weaponising microbes for peace. Microbial Biotechnology. doi.org/10.1111/1751-7915.14224.

In a first, scientists have used bat cells to create bat induced pluripotent stem cells (iPSCs), which can …

In a first, scientists have used bat cells to create bat induced pluripotent stem cells (iPSCs), which can now serve as a tool to study the connections between bats and the viruses they host. Many viruses, including Ebola, Marburg, Nipah, MERS-CoV, SARS-CoV, and SARS-CoV-2 have been linked to different species of bats, even if other animals have acted as infection reservoirs. Bats are known to harbor more viruses than other mammals, and bats themselves are the second most diverse order of mammals on Earth (after rodents). Even though we know that novel pathogens may emerge from bats to infect humans, bat virus ecology has been poorly understood. This model can help change that.

Scanning electron micrograph of Ebola virus particles (purple) both budding and attached to the surface of infected VERO E6 cells (green)/ Image captured at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Credit: NIAID

Researchers can now use bat iPSCs to learn more about the growth and spread of viruses that bats carry. Bats also have special characteristics that enable them to carry these viral reservoirs without getting sick, and this model may help us understand how they defend themselves from disease. The work has been reported in Cell.

The scientists used cells from the wild greater horseshoe bat (Rhinolophus ferrumequinum), the most common asymptomatic host of coronaviruses, including relatives of SARS-CoV-2, to create induced pluripotent stem cells. These cells are made by changing the expression of a few genes of skin or blood cells, such that they resemble newborn stem cells. The bat iPSCs can be used to generate any other bat cell type.

Bat iPSCs were compared to iPSCs from other mammals, revealing a unique biology, noted study co-author Adolfo García-Sastre, Ph.D., a Professor of Medicine and Director of the Global Health and Emerging Pathogens Institute at Icahn Mount Sinai. “The most extraordinary finding was the presence of large virus-filled vesicles in bat stem cells representing major viral families, including coronaviruses, without compromising the cells’ ability to proliferate and grow. This could suggest a new paradigm for virus tolerance as well as a symbiotic relationship between bats and viruses.”

This study has suggested that bats have certain biological mechanisms that allow them to tolerate many viral sequences, and bats could be more entwined with viruses that we knew, noted senior study author Thomas Zwaka, MD, Ph.D., a Professor at the Icahn School of Medicine at Mount Sinai. Bats can survive the presence of viruses that often kill humans, such as Marburg, which may be due to a modulation of their immune response, added Zwaka.

This study could help researchers answer some crucial questions, and protect humans from emerging viruses; we may be able to use tactics like those in bats to prevent viral infection or illness. Ultimately, it could help scientists learn why bats hold a unique position as viral reservoirs, noted Dr. García-Sastre. “And that knowledge could provide the field with broad new insights into disease and therapeutics while preparing us for future pandemics.”

Bat stem cell research will “directly impact every aspect of our understanding of bat biology, including bats’ amazing adaptations of flight and ability to locate distant or invisible objects through echolocation, the location of objects reflected by sound, as well as their extreme longevity and unusual immunity,” Zwaka concluded.

Sources: The Mount Sinai Hospital, Cell

Carmen Leitch

For many years, there was debate about whether chronic fatigue syndrome was a ‘real’ disorder. It took time, …

For many years, there was debate about whether chronic fatigue syndrome was a ‘real’ disorder. It took time, but patients were eventually validated, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was shown to be a disease that can cause various symptoms including fatigue, pain, cognitive difficulties, sleep problems, gastrointestinal issues, and post-exertional malaise. The causes of ME/CFS are still unclear and there is no way to treat it. But the gut microbiome has been shown to play a crucial role in many aspects of human health and disease, and now scientists have shown that the gut microbiomes of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) differ from those of healthy individuals. Two studies reported in Cell Host & Microbe have outlined these differences, showing that they might be used to diagnose ME/CFS. The gut microbiome may also present a treatment opportunity.

Image credit: Pixabay

In one of the studies, researchers assessed the gut bacteria of 106 people with ME/CFS and 91 healthy controls by analyzing stool samples. This research showed that the diversity of species, quantity of microbes, metabolic interactions, and relationships among the gut microbes were different from controls.

ME/CFS patients had unusually low levels of several types of bacteria, including Eubacterium rectale and Faecalibacterium prausnitzii, which generate the short-chain fatty acid butyrate. Previous research has shown that butyrate, a microbial metabolic byproduct, plays a crucial role in gut health maintenance. Butyrate provides a source of energy for cells lining the gut, aids in protecting the cells from disease, and supports the immune system in the gut.

Additional work showed that the reduction of certain bacteria levels was linked to decreases in butyrate production. With fewer butyrate-producing bacteria present, there were other species to fill the void. ME/CFS patients had higher levels of nine microbes, including two that have been linked to autoimmune disorders and inflammatory bowel disease – Enterocloster bolteae and Ruminococcus gnavus.

Symptoms of fatigue were found to increase as levels of F. prausnitzii decreased in ME/CFS patients, which suggests that disease severity may depend on gut microbe levels. People with ME/CFS also had low levels of a microbe that generates acetate.

Biochemical processes in the gut, which are influenced by relationships among gut microbes, were also notably different from controls; the bacterial network seems to be totally altered in ME/CFS patients.

The second report analyzed differences in the microbiomes of ME/CFS patients in different stages of disease. Health data, blood, and stool samples were analyzed from 149 ME/CFS patients; 74 of them had been diagnosed within the previous four years and were classified as short-term, while 75 had been diagnosed over a decade prior and were long-term. There were 74 healthy controls included in this work.

Those who were short-term had less diversity in their microbiomes and significantly lower levels of species that generate butyrate. Long-term patients had more stable microbiomes that were more similar to healthy controls, even while these individuals had more severe symptoms and worse metabolic disturbances. In all ME/CFS patients, tryptophan metabolism was decreased.

This work has shown that there could be biomarkers for ME/CFS in the microbiome, which could also help classify the disease and may lead to treatments, though a lot more research will be needed before those tests and treatments are realized.

Sources: National Institutes of Health, Cheng Guo et al Cell Host & Microbe 2023, Ruoyun Xiong et al Cell Host & Microbe 2023

Carmen Leitch

We now know that even mild cases of COVID-19 can lead to long COVID, in which symptoms linger …

We now know that even mild cases of COVID-19 can lead to long COVID, in which symptoms linger for weeks, months, or longer, detracting from people’s ability to lead a normal life. Scientists are starting to characterize long COVID, which will help us learn more about how it arises and find ways to treat the disorder. A major effort by the National Institutes of Health, Researching COVID to Enhance Recovery (RECOVER) is now ongoing (and still recruiting); it has used electronic health records to look for symptom patterns in about 35,000 Americans who were infected with SARS-CoV-2 (the virus that causes COVID-19) and went on to develop symptoms that are known as long COVID.

Novel Coronavirus SARS-CoV-2  Colorized scanning electron micrograph of an apoptotic cell (blue) heavily infected with SARS-CoV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

It’s not unusual for viral infections to cause lingering symptoms in people, and they can be hard to define and treat. In the case of COVID-19, these symptoms have been called post-acute SARS-CoV-2 infection (PASC), or more commonly, long COVID. It’s been estimated that as many as 40 percent of Americans have had long COVID symptoms at some point.

There are many physiological issues that have been linked to long COVID, including loss of taste or smell, fatigue, headache, dizziness, depression, anxiety, cough, chest pain, joint pain, muscle pain, or gastrointestinal distress, among other symptoms.

A new RECOVER study published in Nature Medicine has outlined four major subtypes of long COVID, which are characterized by different symptom clusters.

  • One subtype involves heart, circulation, and kidney dysfunction, and a high proportion of these patients were infected in the initial months of the US pandemic. This group accounted for about 34 percent of long COVID patients. The sex ratio is roughly one-to-one in this group, and patients were older, with a median age of 65. About 61 percent had been hospitalized for COVID.
  • A second subtype is related to anxiety, sleep disorders, headache, chest pain, and respiratory problems; about two-thirds of these individuals were women. Around 33 percent of long COVID patients were in this category. Their median age was 51; and fewer of them, about 31 percent, had been hospitalized for COVID. The people in this group tended to get COVID between November 2020 and November 2021. Many of them had underlying respiratory conditions like asthma or chronic obstructive pulmondary disorder (COPD).
  • The final two subtypes did not include as many patients. About 23 percent of patients were in the third group, with musculoskeletal and nervous system issues.
  • The final subtype, which included ten percent of patients, experienced digestive and respiratory symptoms.

“RECOVER is aiming to rapidly elucidate what is happening in long COVID. Looking at how cases cluster can profoundly impact the prognosis and care of patients,” said co-senior study author Dr. Rainu Kaushal, chair of the Department of Population Health Sciences at Weill Cornell Medicine, among other appointments.

“This sex difference in long-COVID risk is consistent with prior research, but so far very few studies have even tried to uncover the mechanisms underlying it,” noted study leader Dr. Fei Wang, an associate professor of population health sciences at Cornell.

Now the investigators want to follow up on these findings to look for risk factors that predispose people to certain subtypes of long COVID, and identify existing medications that might be repurposed to use as long COVID treatments.

Another part of the RECOVER initiative has also used machine learning to analyze long COVID trends. Reporting in eBioMedicine, this work indicated that there are links between underlying conditions such as diabetes or hypertension and the risk of long COVID.

Sources: Cornell University, Nature Medicine

Carmen Leitch

While about 30,000 Americans are confirmed to have Lyme disease every year, the Centers for Disease Control and …

While about 30,000 Americans are confirmed to have Lyme disease every year, the Centers for Disease Control and Prevention (CDC) has estimated that the number could be as high as 476,000. Lyme disease is also becoming more common in other countries, with an estimated 200,000 cases in Western Europe every year. Ixodes tick bites transmit the bacteria that cause Lyme disease; these pathogens are varieties of Borrelia bacteria, including Borrelia burgdorferi in the US and B. afzelii and B. garinii in Europe. The disease causes rash, fever, joint pain, and can lead to nervous system and heart complications.

A digitally colorized SEM image at high magnification, depicting three Borrelia burgdorferi bacteria, derived from a pure culture. / Credit: CDC/ Claudia Molins / Photo Credit: Jamice Haney Carr

Now scientists may have learned how Borrelia bacteria migrate from the site of a bite to an infected person’s bloodstream. For this work, researchers created a specialized 3D tissue model that was meant to mimic a human blood vessel, the skin around it, and the tick bite. High-resolution optical imaging was used to monitor the bacteria. This showed that  B. burgdorferi basically uses trial and error to find an opening in spaces called junctions, which line blood vessels and can be found near the sites of bites. Once the pathogenic microbes break through, they can move into the bloodstream and on to other tissues and organs. The findings have been reported in Advanced Science.

If Borrelia could not find a junction right away, they kept searching until they found one, said senior study author Peter Searson, a professor at the Whiting School of Engineering of Johns Hopkins University. “The bacteria spend an hour or two using this behavior to find their way into the blood vessels, but once there, they are in circulation in a matter of seconds.”

Understanding how these bacterial pathogens spread could help scientists develop treatments for Lyme disease, which can cause symptoms that last for months or even years. It may be possible to prevent the pathogens from moving beyond the site of the initial bite.

The researchers have experience developing vascular models with tissue engineering, and they applied what they knew to make a dermal tissue model.

“We also believe that the kind of human tissue-engineered model we created can be broadly applied to visualize the details of dynamic processes associated with other vector-borne diseases and not just Lyme disease,” Searson added.

Sources: CDC, WHO, Johns Hopkins University, Advanced Science

Carmen Leitch

For decades, humans have relied on antibiotics to eliminate bacterial infections, and for a long time, those antibiotics …

For decades, humans have relied on antibiotics to eliminate bacterial infections, and for a long time, those antibiotics worked reliably. But microbes, like other forms of life, can evolve to find ways around the things that impede their growth and survival. Pathogenic bacteria are doing that with antibiotics, and while scientists are searching for new antibiotic compounds that can be used therapeutically, creating new medicines presents many challenges and can take a long time. Bacteriophages, which are viruses that only infect bacterial cells, might be a solution to the problem of antibiotic resistance. But if they are going to work against infections in humans, we need to know more about them first.

A digitally colorized SEM image of two carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteria (yellow) interacting with a type of human white blood cell called a neutrophil (green) / Credit: National Institute of Allergy and Infectious Diseases (NIAID)

Scientists have now used a variety of methods including cryo-electron microscopy, machine learning, and simulations to characterize the structure and function of a bacteriophage that normally lives in the human gastrointestinal tract. The phage, called ϕKp24, could be useful against multidrug resistant strains of Klebsiella pneumoniae. The work has been reported in Nature Communications.

The World Health Organization has designated K. pneumoniae a priority 1 pathogen, meaning that it is critical to create new antibiotics that can eliminate these infections. There are over one hundred genetically distinct types of K. pneumoniae, which can cause bacteremia, urinary tract infection, pneumonia, and other diseases. Immunocompromised individuals are at particular risk.

Although bacteriophages can destroy multi-drug resistant K. pneumoniae, most of these phages are very individualized, and will only attack specific strains of the pathogen. This study aimed to reveal more about the ϕKp24 phage, which may be able to attack multiple strains of K. pneumoniae.

The study authors suggested that ϕKp24 may be a good candidate for the development of phage therapy for humans.

“The problem with phage therapy is that bacteriophages don’t work on all bacteria, even from the same species. In contrast to many known bacteriophages, this one is special because it works on many different subtypes. This makes it a good candidate for phage therapy,” explained corresponding study author Professor Ariane Briegel of Institute Biology Leiden. “By learning more about how the bacteriophage works, we can hopefully treat people with it in the future.”

Sources: Leiden University, Nature Communications

Carmen Leitch

Global Access Diagnostics joins consortium to co-develop on-farm rapid test for calf pneumonia, RaDiCal

Global Access Diagnostics (GADx), a social enterprise prioritizing equitable access to diagnostics and driving local manufacturing, today announced the development of RaDiCal, a one-step molecular lateral flow test to enable rapid diagnosis of pneumonia, one of the most significant diseases affecting calves. The test is being developed through a collaborative consortium, including representatives from the University of Surrey, University of Glasgow, Cardiff University, and Westpoint Farm Vets, to provide a low-cost platform to be used by vets or farmers on-farm. The project is funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

Pneumonia is one of the most significant diseases affecting calves, costing the UK cattle industry an estimated £50 million a year 1. Resulting from GADx’s participation in a BBSRC Endemic Livestock Disease Priming Partnerships workshop and driven by challenges outlined by farmers, the consortium is combining expertise in microbiology, veterinary infectious disease, and diagnostic test development to create RaDiCal. The test is a pioneering molecular lateral flow platform which can be linked to a mobile phone digital platform for easy interpretation of results, enabling farmers and vets to diagnose calves on-farm, and subsequently take rapid and informed action to facilitate improved disease management and support responsible antibiotic stewardship.

Dr Alison Wakeham, Head of Agriculture and Animal Health, GADx, said: “GADx’s expertise in lateral flow technology allows us to support a variety of disease areas. By applying our platform within the livestock industry, we are glad to be able to help improve disease management for one of the most significant diseases affecting calves. Working alongside other experts in this field through the consortium and with the support of BBSRC funding, we are looking forward to progressing the project and bringing the transformative test to market. Being able to accurately diagnose and treat early in the disease cycle is critical to prevent spread and control outbreaks.”

Professor Mark Chambers, Professor of Microbiology and Disease Intervention, University of Surrey, who is leading the project, commented: “The University of Surrey is delighted to be leading the RaDiCal project and will be using its experience of veterinary infectious diseases and test development within an exciting consortium of other academics and representatives from industry, large animal veterinary practice, and farmers themselves at the sharp end of managing calf pneumonia. Through this close partnership and on-going consultation we shall ensure we develop a test that meets the needs of the cattle industry.”

Abi Reader, project partner, dairy farmer, Goldsland Farm, Chair NFU Cymru Milk Board and Chair CHeCS, added: “Calf Pneumonia puts an enormous burden on UK dairy farmers, causing increased veterinary costs and farming losses. RaDiCal will help reduce this impact and support farmers by enabling early intervention and improved calf welfare.”

To support this research, the University of Surrey School of Veterinary Medicine is looking for veterinary surgeons who work with calves to share their experiences of using diagnostic tests and managing calf pneumonia.

If you would like to participate, please complete this short, anonymous survey:

English version – https://cardiff.onlinesurveys.ac.uk/calfrapidtest

Welsh version – https://cardiff.onlinesurveys.ac.uk/prawfcyflym

For more information about the project, please contact: Mark Chambers ([email protected])

  1. https://ahdb.org.uk/knowledge-library/pneumonia-in-calves