Category Archives: Microbiology

COVID-19 vaccine may be lifesaving for pregnant woman and their unborn children

Stillbirth is a recognized complication of COVID-19 in pregnant women caused by harmful changes to the placenta induced by the virus. Termed SARS-CoV-2 placentitis, it can render the placenta incapable of providing oxygen to the fetus, leading to stillbirth and neonatal death. Researchers now suggest that pregnant women who get the COVID-19 vaccine may be protected from SARS-CoV-2 placentitis and stillbirth. In a new article published in the American Journal of Obstetrics & Gynecology, researchers conclude that the vaccine not only protects pregnant women but may also be lifesaving for their unborn children.

The extensive examination of published literature involved reviewing nearly 100 papers looking at COVID-19’s impacts on pregnant women and the effects on the placenta and outcome. Sarah Mulkey, M.D., Ph.D., a prenatal-neonatal neurologist in the Division of Prenatal Pediatrics at Children’s National Hospital and co-author of the article, says the findings make a strong case for vaccination.

“The COVID-19 virus fortunately does not cause like other viruses such Zika, but it can cause to the placenta that can result in stillbirth and other ,” says Dr. Mulkey. “I hope patients who are pregnant or planning to become pregnant can learn how the COVID vaccine may help keep them and their baby healthy throughout pregnancy from some of the worst effects of this virus.”

While stillbirths can have many causes, the data analyzed supports that the COVID-19 vaccine is beneficial for pregnancies and for reducing the risk of stillbirth by reducing the risk of the virus impacting the placenta.

“In the multiple reports of SARS-CoV-2 placentitis that have been associated with stillbirths and neonatal deaths, none of the mothers had received COVID-19 vaccinations,” says David Schwartz, M.D., lead author, epidemiologist and perinatal pathologist. “And although not constituting proof, we’re not aware, either personally, via collegial networks, or in the published literature, of any cases of SARS-CoV-2 placentitis causing stillbirths among having received the COVID-19 vaccine.”

Earlier in 2022, Dr. Schwartz led a team from 12 countries that found SARS-CoV-2 placentitis destroyed an average of 77.7% of placental tissue, resulting in placental insufficiency and fetal death, all occurring in unvaccinated mothers.

Fortunately, the large majority of pregnancies affected by a COVID-19 infection do not result in stillbirth. The development of SARS-CoV-2 placentitis is complex and likely involves both viral and immunological factors. The characteristics of a SARS-CoV-2 variant may also affect risk.

“Placental pathology is an important component in understanding the pathophysiology of SARS-CoV-2 infection during pregnancy,” says Dr. Mulkey

As part of the Congenital Infection Program at Children’s National, Dr. Mulkey has been following infants born to mothers who had SARS-CoV-2 infection during pregnancy since the beginning of the pandemic. She will present the results of the early neurodevelopment of these infants at ID Week in Washington, D.C., on Oct. 22, 2022. Dr. Mulkey will also lead the neurodevelopmental follow-up of a large cohort of infants born to mothers with SARS-CoV-2 infection during pregnancy to better understand any long-term neurological effects to offspring.

The study builds upon Dr. Mulkey’s on Zika virus infection in pregnancy and long-term impacts on the child.

More information:
David A. Schwartz et al, SARS-CoV-2 Placentitis, Stillbirth and Maternal COVID-19 Vaccination: Clinical-Pathological Correlations, American Journal of Obstetrics and Gynecology (2022). DOI: 10.1016/j.ajog.2022.10.001

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White House: Get new booster by Halloween for safer holidays

The White House on Tuesday said eligible Americans should get the updated COVID-19 boosters by Halloween to have maximum protection against the coronavirus by Thanksgiving and the holidays, as it warned of a “challenging” virus season ahead.

Dr. Ashish Jha, the White House COVID-19 coordinator, said the U.S. has the tools, both from vaccines and treatments, to largely eliminate serious illness and death from the virus, but stressed that’s only the case if people do their part.

“We are not helpless against these challenges,” he said. “What happens this winter is up to us.”

So far the Centers for Disease Control and Prevention says only about 11.5 million Americans have received the updated shots, which are meant to provide a boost of protection against both the original strain of COVID-19 and the BA.5 variant that is dominant around the world. Jha said studies suggest that if more Americans get the updated vaccines, “we could save hundreds of lives each day this winter.”

More than 330 people die on average each day of COVID-19, according to CDC data, with the U.S. death toll standing at over 1.05 million.

Jha acknowledged the slower pace of vaccinations, saying, “we expected September to be a month where it would just start picking up.” He added that the White House expects more Americans to get the updated boosters this month around the time when they get their annual flu shots. He also emphasized that they should look to get them soon to be protected when they gather with family and friends.

“I think people should get vaccinated before Halloween,” he said.

Jha criticized Congress, which has refused the White House’s $22 billion for virus response, saying that has kept the U.S. from building a stockpile of tests to use in the event of a new surge.

“You can’t fight a without resources,” he said, “and congressional inaction is really costly.”

© 2022 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed without permission.

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Black History Month 2022: who has inspired you?

Black History Month 2022: who has inspired you?

Posted on October 12, 2022   by Microbiology Society

The UK’s Black History Month takes place every October. Back in 2020, we looked at some of the achievements of black microbiologists, including Professor Ruth Ella Moore, Dr Alan Powell Goffe, Professor William Augustus Hinton and Dr Faith Uwadiae. This year, to celebrate the newly formed Members Panel, we asked panel member, Dr Aliyah Debbonaire, to tell us about a black scientist from history who has inspired her, for what reasons and the impact they have had on her life.


iStock/Vitalii Abakumov

Person smiling at camera
© Aliyah Debbonaire

There are numerous scientists to choose from when writing a profile on inspirational people for Black History Month, but given my background, career and personal health, I felt I had to choose Dr Percy Lavon Julian.

I was never formally taught about Dr Julian’s work, but discovered him on a Twitter thread about inspirational scientists, realising gradually quite how much his work had influenced my life. His research contributed to the production of many life-saving medications, without which I would not be here. Briefly, he pioneered processes to chemically synthesise useful compounds from plants on a large scale. His work influenced the mass production of birth control pills and corticosteroids.

Steroids, in particular, have changed my life, having been diagnosed with asthma, eczema and food allergies as a child. Every morning, I begin my day by taking inhalers that may not be so readily available without his work and without which I would not be able to live the life I do now. Family members who have been diagnosed with cancer have had their treatment symptoms eased with steroid use. To combat my daughter’s eczema, we use hydrocortisone cream.

Exploiting naturally produced compounds in this way is called bioprospecting which formed the first five years of my career in microbiology. During my PhD, I identified novel antimicrobial compounds from microbes in extreme environments, in this case, the cryosphere. Stories like Dr Julian’s served as an inspiration throughout the project, not to mention the use of inhalers greatly helped me to collect environmental samples from rather cold (obviously) glaciers!

Dr Julian’s life story is a fascinating read; I would encourage others to look into the many barriers he faced in science, as well as personal controversies and the almost serendipitous nature of the discovery of small crystals in experiments that turned out to be invaluable in steroid production. Histories like these highlight the truly interdisciplinary nature of scientific research. Some scientists may identify novel compounds, others may work tirelessly to optimise their mass production, or in this case, make more readily available intermediates used in mass scale production.

I would also encourage anyone who has taken any of the numerous medications influenced by his research to consider the history of their production. How many other minority scientists may have been involved in their discovery, development and proliferation? Were they mentioned throughout your education? Could you raise their profile? In an area of science so focussed on examining the diversity of chemical compounds, is there anything you can do to increase the diversity of scientists where you work?

Find out more about the Members Panel Aliyah is part of and their aim to provide a platform for our members from underrepresented groups. If you would like to contribute content for an awareness day, week or month, read more about how to get involved.

Clinical trial to test the safety, efficacy of bacteriophages for treating P. aeruginosa infections in CF patients

Cystic fibrosis (CF) is an inherited disorder that causes severe damage to the lungs and other organs in the body. Nearly 40,000 children and adults in the United States live with CF, an often difficult existence exacerbated by an opportunistic bacterium called Pseudomonas aeruginosa, which is a major cause of chronic, life-threatening lung infections.

P. aeruginosa infections are not easily treated. The pathogen can be resistant to most current antibiotics. However, an early-stage clinical trial led by scientists at University of California San Diego School of Medicine, with collaborators across the country, has launched to assess the safety and efficacy of treating P. aeruginosa lung infections in CF patients with a different biological weapon: bacteriophages.

Bacteriophages are viruses that have evolved to target and destroy specific bacterial species or strains. Phages are more abundant than all other life forms on Earth combined and are found wherever bacteria exist. Discovered in the early 20th century, they have long been investigated for their therapeutic potential, but increasingly so with the rise and spread of antibiotic-resistant bacteria.

In 2016, scientists and physicians at UC San Diego School of Medicine and UC San Diego Health used an experimental intravenous phage therapy to successfully treat and cure colleague Tom Patterson, PhD, who was near death from a multidrug-resistant bacterial infection. Patterson’s was the first documented case in the U.S. to employ intravenous phages to eradicate a systemic bacterial infection. Subsequent successful cases helped lead to creation of the Center for Innovative Phage Applications and Therapeutics (IPATH) at UC San Diego, the first such center in North America.

In 2020, IPATH researchers published data from 10 cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections, all at UC San Diego. In 7 of 10 cases, there was a successful outcome.

The new phase 1b/2 clinical trial advances this work. The trial is co-led by Robert Schooley, MD, professor of medicine and an infectious disease expert at UC San Diego School of Medicine who is co-director of IPATH and helped lead the clinical team that treated and cured Patterson in 2016.

It will consist of three elements, all intended to assess the safety and microbiological activity of a single dose of intravenous phage therapy in males and non-pregnant females 18 years and older, all residing in the United States.

The dose is a cocktail of four phages that target P. aeruginosa, a bacterial species commonly found in the environment (soil and water) that can cause infections in the blood, lungs and other parts of the body after surgery.

For persons with CF, P. aeruginosa is a familiar and sometimes fatal foe. The Cystic Fibrosis Foundation estimates that roughly half of all people with CF are infected by Pseudomonas. Previous studies have indicated that chronic P. aeruginosa lung infections negatively impact life expectancy of CF patients, who currently live, on average, to approximately 44 years.

In the first stage of the trial, two “sentinel subjects” will receive one of three dosing strengths of the IV bacteriophage therapy. If, after 96 hours and no adverse effects, the second stage (2a) will enroll 32 participants into one of four arms: the three doses and a placebo.

After multiple follow-up visits over 30 days and an analysis of which dosing strength exhibited the most favorable safety and microbiologic activity, i.e. most effective at reducing P. aeruginosa, stage 2b will recruit up to 72 participants to either receive that IV dose or a placebo.

Enrollment will occur at 16 cystic fibrosis clinical research sites in the United States, including UC San Diego. It is randomized, double-blind and placebo-controlled. The trial is being conducted through the Antibacterial Resistance Leadership Group and funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, with additional support for the UC San Diego trial site from the Mallory Smith Legacy Fund.

Mallory Smith was born with cystic fibrosis and died in 2017 at the age of 25 from a multidrug-resistant bacterial infection following a double lung transplant.

Mallory’s death was a preventable tragedy. We are supporting the IPATH trial through Mallory’s Legacy Fund because Mark and I deeply believe in the promise of phage therapy to save lives by combatting multidrug-resistant bacteria.”

Diane Shader Smith, Mother

In an article published in 2020 in Nature Microbiology, Schooley and Steffanie Strathdee, PhD, associate dean of global health sciences and Harold Simon Professor in the Department of Medicine and IPATH co-director, describe phages as “living antibiotics.”

As such, said Schooley, researchers need to learn how to best use them to benefit patients through the same systematic clinical trials employed to evaluate traditional antibiotics.

The primary objectives of the new trial are first to determine the safety of a single IV phage dose in clinically stable patients with CF who are also infected with P. aeruginosa, said Schooley.

“Second, it’s to describe the microbiological activity of a single IV dose and third, to assess the benefit-to-risk profile for CF patients with P. aeruginosa infections. This is one study, with a distinct patient cohort and carefully prescribed goals. It’s a step, but an important one that can, if ultimately proven successful, help address the growing, global problem of antimicrobial resistance and measurably improve patients’ lives.”

Estimated study completion date is early 2025.

$2.5 million CDC contract to fund one of the largest SARS-CoV-2 surveillance programs in the U.S.

A team led by Scripps Research scientists has been awarded a contract by the U.S. Centers for Disease Control & Prevention (CDC) in support of one of the largest SARS-CoV-2 surveillance programs in the United States.

The two-year, $2.5 million contract will fund the large-scale, near real-time sequencing of SARS-CoV-2 isolates from hospitals and local public health agencies in San Diego and nearby northwestern Mexico, and the development of software for tracking the evolution and geographical spread of SARS-CoV-2 variants.

The contract, an extension of one originally awarded in 2020, will be carried out by the San Diego Epidemiology and Research for COVID Health (SEARCH) Alliance, which was co-founded by Scripps Research, the University of California San Diego (UC San Diego), and Rady Children’s Hospital-San Diego.

CDC’s support for SEARCH’s genomic surveillance program has already led to significant COVID-19 public health advances as well as new science on SARS-CoV-2, and we expect much more progress in both areas as a result of this new award.”

Kristian Andersen, PhD, Principal Investigator, Professor, Department of Immunology and Microbiology at Scripps Research

Since the start of the pandemic, SEARCH has been conducting genomic surveillance of SARS-CoV-2 using clinical samples collected at San Diego hospitals and from sources across the border in Baja California. SEARCH has also developed key protocols and analysis tools to track the emergence and spread of SARS-CoV-2 variants in wastewater. Moreover, SEARCH investigators are actively involved in understanding the emergence of SARS-CoV-2, and in several high-profile publications have found evidence for an initial spread from animals sold at the Huanan Market in Wuhan, China.

SEARCH’s efforts involve multiple collaborations, including with the CDC, San Diego County’s Health & Human Services Agency, the California Department of Public Health, Sharp Health, Scripps Health, the viral surveillance company Helix, and the Salud Digna healthcare network in Mexico. Since the start of the pandemic, these efforts have yielded publications and analyses of more than 70,000 SARS-CoV-2 sequences.

Under the new contract, SEARCH will accelerate its virus-sequencing workflow to produce more timely and actionable information on local virus spread and evolution-;including the emergence of new variants and subvariants of concern.

“The current process of sampling, sequencing and analyzing a batch of virus samples from local hospital cases and wastewater treatment plants can take several weeks,” says Mark Zeller, PhD, project scientist in the Andersen lab. “We’re aiming to get that down to a matter of days, which would enable us to monitor the transmission chains in local outbreaks in near real-time.”

Working with the County of San Diego, the state of California and Mexican public health labs, the researchers will also continue to analyze the transmission of SARS-CoV-2 across the busy California-Baja border. Additionally, they’ll expand their genomic surveillance efforts to additional Mexican border states and popular tourist destinations, including Puerto Vallarta. The team will continue to post their analyses on SEARCH’s online dashboards.

The project includes the further development of open-source software tools to support the tracking of local SARS-CoV-2 evolution and transmission.

“The tools we’ve developed in recent years are already being used widely by the public health community for SARS-CoV-2 sequencing and analysis,” says Joshua Levy, PhD, postdoctoral research associate in the Andersen lab. “Under this new contract, we will be developing the technology to permanently transform how genomic surveillance will be used to strengthen our public health response.”

These open-source software tools are available at The SEARCH Alliance’s SARS-CoV-2 surveillance dashboards are at

Duke receives federal funding for HIV vaccine research

The Duke Human Vaccine Institute (DHVI) and the Department of Surgery at Duke University School of Medicine received a grant from the National Institute of Allergy and Infectious Diseases for HIV vaccine research that could total $25.9 million with full funding over five years.

The funding supports a multi-institutional effort called The Consortium for Innovative HIV/AIDS Vaccine and Cure Research that is built around two areas of scientific focus: identification of the components and the mechanisms of protection of preventive vaccines; and the use of the newly identified preventive vaccines along with other immune therapies in advancing potential treatments and/or cures.

The grant’s principal investigators are Guido Ferrari, M.D., a professor in the Department of Surgery and research professor in the Department of Genetics and Microbiology, and Wilton Williams, Ph.D., an associate professor in the departments of Surgery and Medicine, and assistant professor in the Department of Immunology at Duke University School of Medicine.

The researchers will lead work that builds upon ongoing HIV vaccine development research at DHVI and expands investigations of vaccine strategies, including innovative mRNA approaches that induce protective immune responses in non-human primate models.

This grant is synergistic with everything going on at Duke, notably the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) initiative to design an HIV vaccine. We are excited about the wonderful science that will be done in the context of this grant. It expands the capacity at Duke, UNC and others who are collaborating on this effort to move forward with both vaccines and potential cures.”

Barton Haynes, Director of the DHVI

Combining vaccine approaches with cure efforts is designed to stimulate innovative collaborations toward both. Studies in nonhuman primates will investigate how effective HIV/AIDS vaccines protect from initial infection and systemic infection.

Vaccines and other immune interventions will also be used as cure strategies with the goal of eliminating all the infection in the cells. While advances have been made in boosting cellular and antibody immunity, it remains unclear whether the boosted immune response can prevent reinfection after antiretroviral treatments are stopped. With the newly funded grant, the researchers hope to answer that and other questions.

“This grant enables us to do something current vaccine research is not funded to do – explore vaccines with a mission to cure,” Williams said. “Right now, it’s either prevention or cure, and we want to achieve a combination of those things.”

Ferrari said vaccine research has advanced far enough that researchers can now begin applying potential components of vaccines, as well as new technologies such as mRNA vaccine design, to explore ways of eradicating the HIV from infected cells.

“The beauty of mRNA is its ability to be adapted quickly and we can produce it in a timely manner to address new variants, which is important for HIV,” Ferrari said. “We will now focus on how we can capitalize on the current science to eradicate infection.”

“The science underpinning this program has broad applicability, spanning from the immediate goals of eliminating HIV disease, to a more generalizable harnessing of the immune system to prevent emerging infectious diseases, control cancer, and accelerate our understanding of autoimmunity and transplant biology,” said Allan D. Kirk, M.D., Ph.D., chair of the Department of Surgery.

“Our department sees the promise of basic investments like these for transformational approaches to care that do not traditionally fall within a surgical department,” Kirk said. “Drs. Williams and Ferrari are vital members of our translational science community.”

In addition to Williams and Ferrari, collaborators at Duke are Priyamvada Acharya, Mihai Azoitei, Derek Cain, Thomas Denny, Robert J. Edwards, Barton Haynes, David Montefiori, Justin Pollara, Keith Reeves, Wes Rountree, Kevin Saunders, Shaunna Shen, Rachel Spreng, Georgia Tomaras, Kevin Wiehe, Kelly Cuttle and Cynthia Nagle.

Study partners include Katharine Barr, Michael Betts, Beatrice Hahn, George Shaw, Drew Weissman at the University of Pennsylvania; Richard Dunham and David Margolis at the University of North Carolina at Chapel Hill; Sampa Santra at Harvard University; Andrew McMichael, Persephone Borrow and Geraldine Gillespie at Oxford University; Bette Korber and Kshitij Wagh at Los Alamos National Laboratory; and Mark Lewis at BIOQUAL.

New study identifies potential therapeutic target for colonic disorders

Colonic motility disorders, especially problems associated with constipation and diarrhea, are common in adults and children, greatly impacting quality of life. A new study in The American Journal of Pathology identifies neuropilin 2 (NRP2) as a novel regulator of distal colonic smooth muscle motility. Its ability to regulate cytoskeletal tone and restrain abnormal smooth muscle contraction may provide opportunities in the future to inhibit or activate signaling and thereby regulate smooth muscle activity in patients suffering from colonic motility disorders.

“Normal visceral activity is central to the function of many body systems including the gastrointestinal and urinary tracts, but it is much less studied than ,” explained co-lead investigator Maryrose P. Sullivan, Ph.D., Department of Surgery, Harvard Medical School; and Division of Urology, VA Boston Healthcare System.

“Earlier studies by our group that showed robust expression of Nrp2 in smooth muscle of the colon prompted us to understand its functional significance in contraction and colonic .”

The investigators found extensive NRP2 expression in the distal colon that was especially prominent in circular and longitudinal smooth muscles in both humans and mouse models. They used genetically modified mice to determine the impact of Nrp2 deletion on contractility of the colon. Having demonstrated extensive expression of Nrp2 in smooth muscle of the gastrointestinal tract, they determined the functional consequences of Nrp2 gene deletion in vitro and motility analysis in intact mice.

Their findings showed colonic tissues displayed increased evoked contraction in mice with global or smooth muscle–specific deletion of Nrp2. Mice with inducible, smooth muscle–specific Nrp2 deletion also showed an increase in colonic motility.

“We were intrigued by the emergence of functional changes as early as a week after deletion of Nrp2,” said co-lead investigator Rosalyn M. Adam, Ph.D., Urological Diseases Research Center, Boston Children’s Hospital; and Department of Surgery, Harvard Medical School, Boston.

“The relatively rapid detection of differences in contractile behavior of colonic muscle argues against major structural changes to the tissue, but rather suggests changes in cellular signaling. Delineating the signaling networks regulated by Nrp2 in smooth muscle is a major focus of our ongoing research.”

Dr. Sullivan and Dr. Adam observed that their study provides an important addition to understanding mechanisms of regulation of visceral smooth muscle and suggests that Nrp2 may be an actionable target in diseases characterized by abnormal smooth muscle contraction.

“Although studies in patients are many years away, ongoing studies in our group are focused on development of small molecule inhibitors designed to inhibit Nrp2. These efforts may provide opportunities in the future to inhibit signaling via Nrp2 and regulate smooth muscle activity in patients. This is particularly relevant for diseases in which visceral smooth is impaired, since effective pharmacotherapy for these conditions is not currently available,” they noted.

Alterations in colonic motility can result from a variety of conditions, including congenital anomalies such as Hirschsprung disease, diabetes, inflammation, infection, gut dysbiosis, and nerve damage secondary to spinal injury. Furthermore, changes in the magnitude and/or coordination of contractile activity throughout the can lead to dysfunctional motility with ensuing disturbances in intestinal flora, inflammation, and nutrient absorption, often with serious health consequences.

More information:
George Lambrinos et al, Neuropilin 2 Is a Novel Regulator of Distal Colon Contractility, The American Journal of Pathology (2022). DOI: 10.1016/j.ajpath.2022.07.013

Journal information:
American Journal of Pathology

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Monoclonal antibody improves cat allergen immunotherapy

An experimental approach to enhancing a standard cat allergy treatment made it more effective and faster acting, and the benefits persisted for a year after treatment ended, a study supported by the National Institutes of Health has found. The findings were published Monday in the Journal of Allergy and Clinical Immunology.

Allergen immunotherapy, often called , is a long-term treatment that decreases for people with conditions such as allergic rhinitis or allergic asthma by reducing their sensitivity to allergens. Achieving persistent symptom relief requires at least three years of allergy shots, however, and does not work for everyone.

“People with chronic allergy symptoms may suffer from reduced productivity and quality of life,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of NIH. “Developing regimens that work better and more quickly than those currently available would provide much-needed relief for many people.”

To that end, NIAID-supported investigators tested whether giving a monoclonal antibody called tezepelumab plus cat allergy shots to people with allergic rhinitis caused by cat allergens would safely provide better and faster long-lasting symptom relief than allergy shots alone. Allergic rhinitis involves inflammation of the nasal membranes and causes symptoms such as sneezing, , stuffy nose, watery eyes, problems with smell, and an itchy nose, mouth, or eyes.

The Phase 1/2 clinical trial, called CATNIP, was led by Jonathan Corren, M.D., and conducted by the NIAID-funded Immune Tolerance Network. Dr. Corren is an associate clinical professor of medicine at the David Geffen School of Medicine at UCLA in Los Angeles. Tezepelumab was donated for the trial by Amgen Inc. of Thousand Oaks, California and AstraZeneca of Gaithersburg, Maryland.

Tezepelumab blocks a protein called thymic stromal lymphopoietin (TSLP), a type of cell-signaling molecule, or cytokine, called an alarmin. Cells that cover the surface of organs like the skin and intestines or that line the inside of the nose and lungs rapidly secrete TSLP in response to signals of potential danger. In allergic disease, TSLP helps initiate an overreactive immune response to otherwise harmless substances like cat dander, provoking airway inflammation that leads to the symptoms of allergic rhinitis.

The CATNIP study enrolled 121 adults ages 18 to 65 years at nine medical centers in eight cities across the United States. The participants were assigned at random to receive either tezepelumab plus subcutaneous cat allergy shots, tezepelumab plus placebo shots, placebo plus allergy shots, or a double placebo. No one knew who received which regimen until the end of the study. The treatment period lasted 48 weeks, and the study team continued to follow participants for a year after treatment ended.

To test how well each regimen worked, the study team gave participants one spritz in each nostril of a containing cat allergen extract six times during the two-year study period. The study team recorded participants’ level of nasal symptoms and airflow through the nose at five, 15, 30 and 60 minutes after receiving the nasal spray and hourly for up to five hours thereafter. In addition, blood and nasal cell samples were collected from participants.

The investigators found that participants’ worst nasal symptoms were 36% lower at the end of treatment in the group that received tezepelumab plus allergy shots compared to the group that received allergy shots alone, and 24% lower a year later. These results show for the first time that adding a cytokine inhibitor to allergy shots can reduce symptoms for an extended period after just one year of treatment, according to the researchers.

An analysis of blood and nasal cell samples revealed that the combination treatment caused changes in gene network activity that reduced the activation of allergy-related immune cells on the inner lining of the nose, helping suppress allergic nasal symptoms.

With the successful outcome of the CATNIP trial, plans are underway for a NIAID-supported Phase 2 trial of tezepelumab plus oral immunotherapy for food allergy. In addition, the CATNIP investigators are further analyzing the study data to understand how tezepelumab plus immunotherapy works at a , to potentially design additional trials that look at more , and to identify the people who may benefit the most from this treatment combination.

More information:
Jonathan Corren et al, Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: a randomized controlled trial, Journal of Allergy and Clinical Immunology (2022). DOI: 10.1016/j.jaci.2022.08.029

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Genetically engineered bacteria make living materials for self-repairing walls and cleaning up pollution

With just an incubator and some broth, researchers can grow reusable filters made of bacteria to clean up polluted water, detect chemicals in the environment and protect surfaces from rust and mold.

I am a synthetic biologist who studies engineered living materials – substances made from living cells that have a variety of functions. In my recently published research, I programmed bacteria to form living materials that can not only be modified for different applications, but are also quick and easy to produce.

Like human cells, bacteria contain DNA that provides the instructions to build proteins. Bacterial DNA can be modified to instruct the cell to build new proteins, including ones that don’t exist in nature. Researchers can even control exactly where these proteins will be located within the cell.

Because engineered living materials are made of living cells, they can be genetically engineered to perform a broad variety of functions, almost like programming a cellphone with different apps. For example, researchers can turn bacteria into sensors for environmental pollutants by modifying them to change color in the presence of certain molecules. Researchers have also used bacteria to create limestone particles, the chemical used to make Styrofoam and living photovoltaics, among others.

A primary challenge for engineered living materials has been figuring out how to induce them to produce a matrix, or substances surrounding the cell, that allows researchers to control the physical properties of the final material, such as its viscosity, elasticity and stiffness. To address this, my team and I created a system to encode this matrix in the bacteria’s DNA.

We modified the DNA of the bacteria Caulobacter crescentus so that the bacterial cells would produce on their surfaces a matrix made of large amounts of elastic proteins. These elastic proteins have the ability to bind to each other and form hydrogels, a type of material that can retain large amounts of water.

When two genetically modified bacterial cells come in close proximity, these proteins come together and keep the cells attached to each other. By surrounding each cell with this sticky, elastic material, bacterial cells will cluster together to form a living slime.

Furthermore, we can modify the elastic proteins to change the properties of the final material. For example, we could turn bacteria into hard construction materials that have the ability to self-repair in the event of damage. Alternatively, we could turn bacteria into soft materials that could be used as fillers in products.

Usually, creating multifunctional materials is extremely difficult, due in part to very expensive processing costs. Like a tree growing from a seed, living materials, on the other hand, grow from cells that have minimal nutrient and energy requirements. Their biodegradability and minimal production requirements allow for sustainable and economical production.

The technology to make living materials is unsophisticated and cheap. It only takes a shaking incubator, proteins and sugars to grow a multifunctional, high-performing material from bacteria. The incubator is just a metal or plastic box that keeps the temperature at about 98.6 degrees Fahrenheit (37 Celsius), which is much lower than a conventional home oven, and shakes the cells at speeds slower than a blender.

Transforming bacteria into living materials is also a quick process. My team and I were able to grow our bacterial living materials in about 24 hours. This is pretty fast compared to the manufacturing process of other materials, including living materials like wood that can take years to produce.

Moreover, our living bacterial slime is easy to transport and store. It can survive in a jar at room temperature for up to three weeks and placed back into a fresh medium to regrow. This could lower the cost of future technology based on these materials.

Lastly, engineered living materials are an environmentally friendly technology. Because they are made of living cells, they are biocompatible, or nontoxic, and biodegradable, or naturally decomposable.

There are still some aspects of our bacterial living material that need to be clarified. For example, we don’t know exactly how the proteins on the bacterial cell surface interact with each other, or how strongly they bind to each other. We also don’t know exactly how many protein molecules are required to keep cells together.

Answering these questions will enable us to further customize living materials with desired qualities for different functions.

Next, I’m planning to explore growing different types of bacteria as living materials to expand the applications they can be used for. Some types of bacteria are better than others for different purposes. For example, some bacteria survive best in specific environments, such as the human body, soil or fresh water. Some, on the other hand, can adapt to different external conditions, like varying temperature, acidity and salinity.

By having many types of bacteria to choose from, researchers can further customize the materials they can create.

Sara Molinari

The Conversation

Microbiome: From Research and Innovation to Market