Tag Archives: Infection

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

18 March, 2023 Admin Leave a comment

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

Center for Genomic Regulation

Microbiology

Harvard Scientists Uncover How the Brain Senses Infection

12 March, 2023 Admin Leave a comment

A recent study led by researchers at Harvard Medical School sheds new light on how the brain becomes aware of the presence of an infection in the body.

The team, through their study of mice, uncovered that a small group of airway neurons play a crucial role in informing the brain about a flu infection. They also observed evidence of a secondary pathway from the lungs to the brain that becomes active during later in the infection.

The study was recently published in the journal Nature.

Although most people are sick several times a year, scientific knowledge of how the brain evokes the feeling of sickness has lagged behind research on other bodily states such as hunger and thirst. The paper represents a key first step in understanding the brain-body connection during an infection.

“This study helps us begin to understand a basic mechanism of pathogen detection and how that’s related to the nervous system, which until now has been largely mysterious,” said senior author Stephen Liberles, professor of cell biology in the Blavatnik Institute at HMS and an investigator at Howard Hughes Medical Institute.

The findings also shed light on how nonsteroidal anti-inflammatory drugs such as ibuprofen and aspirin alleviate influenza symptoms.

If the results can be translated into humans, the work could have important implications for developing more-effective flu therapies.

The Liberles lab is interested in how the brain and body communicate to control physiology. For example, it has previously explored how the brain processes sensory information from internal organs, and how sensory cues can evoke or suppress the sensation of nausea.

In the new paper, the researchers turned their attention to another important type of sickness that the brain controls: sickness from a respiratory infection.

During an infection, Liberles explained, the brain orchestrates symptoms as the body mounts an immune response. These can include broad symptoms such as fever, decreased appetite, and lethargy, as well as specific symptoms such as congestion or coughing for a respiratory illness or vomiting or diarrhea for a gastrointestinal bug.

The team decided to focus on influenza, a respiratory virus that is the source of millions of illnesses and medical visits and causes thousands of deaths in the United States every year.

Through a series of experiments in mice, first author Na-Ryum Bin, HMS research fellow in the Liberles lab, identified a small population of neurons embedded in the glossopharyngeal nerve, which runs from the throat to the brain.

Importantly, he found that these neurons are necessary to signal to the brain that a flu infection is present and have receptors for lipids called prostaglandins. These lipids are made by both mice and humans during an infection, and they are targeted by drugs such as ibuprofen and aspirin.

Cutting the glossopharyngeal nerve, eliminating the neurons, blocking the prostaglandin receptors in those neurons, or treating the mice with ibuprofen similarly reduced influenza symptoms and increased survival.

Together, the findings suggest that these airway neurons detect the prostaglandins made during a flu infection and become a communication conduit from the upper part of the throat to the brain.

“We think that these neurons relay the information that there’s a pathogen there and initiate neural circuits that control the sickness response,” Liberles said.

The results provide an explanation for how drugs like ibuprofen and aspirin work to reduce flu symptoms — and suggest that these drugs may even boost survival.

The researchers discovered evidence of another potential sickness pathway, this one traveling from the lungs to the brain. They found that it appears to become active in the second phase of infection as the virus infiltrates deeper into the respiratory system.

This additional pathway doesn’t involve prostaglandins, the team was surprised to find. Mice in the second phase of infection didn’t respond to ibuprofen.

The findings suggest an opportunity for improving flu treatment if scientists are able to develop drugs that target the additional pathway, the authors said.

The study raises a number of questions that Liberles and colleagues are eager to investigate.

One is how well the findings will translate to humans. Although mice and humans share a lot of basic sensory biology, including having a glossopharyngeal nerve, Liberles emphasized that researchers need to conduct further genetic and other experiments to confirm that humans have the same neuron populations and pathways seen in the mouse study.

If the findings can be replicated in humans, it raises the possibility of developing treatments that address both the prostaglandin- and nonprostaglandin pathways of flu infection.

“If you can find a way to inhibit both pathways and use them in synergy, that would be incredibly exciting and potentially transformative,” Liberles said.

Bin is already delving into the details of the nonprostaglandin pathway, including the neurons involved, with the goal of figuring out how to block it. He also wants to identify the airway cells that produce prostaglandins in the initial pathway and study them in more depth.

Liberles is excited to explore the full diversity of sickness pathways in the body to learn whether they specialize for different types and sites of infection. A deeper understanding of these pathways, he said, can help scientists learn how to manipulate them to better treat a range of illnesses.

Reference: “An airway-to-brain sensory pathway mediates influenza-induced sickness” by Na-Ryum Bin, Sara L. Prescott, Nao Horio, Yandan Wang, Isaac M. Chiu and Stephen D. Liberles, 8 March 2023, Nature.
DOI: 10.1038/s41586-023-05796-0

The study was funded by the National Institutes of Health, the Chan Zuckerberg Initiative, a Banting Postdoctoral Fellowship, and a Harvard Medical School Goldberg Fellowship.

Liberles is a consultant for Kallyope.

Harvard Medical School

Microbiology

Antibiotics can destroy many types of bacteria, but increasingly, bacterial pathogens are gaining resistance to many commonly used …

7 March, 2023 Admin Leave a comment

Antibiotics can destroy many types of bacteria, but increasingly, bacterial pathogens are gaining resistance to many commonly used types. As the threat of antibiotic resistance looms large, researchers have sought to find new antibiotics and other ways to destroy dangerous bacteria. But new antibiotics can be extremely difficult to identify and test. Bacteriophages, which are viruses that only infect bacterial cells, might offer an alternative. Bacteriophages (phages) were studied many years ago, before the development of antibiotic drugs, and they could help us once again.

If we are going to use bacteriophages in the clinic to treat humans, we should understand how they work, and how bacteria can also become resistant to them. Microbes are in an arms race with each other, so while phages can infect bacteria, some bacterial cells have found ways to thwart the effects of those phages. New research reported in Nature Microbiology has shown that when certain bacteria carry a specific genetic mutation, phages don’t work against them anymore.

In this study, the researchers used a new technique so they could actually see a phage attacking bacteria. Mycobacteriophages infect Mycobacterial species, including the pathogens Mycobacterium tuberculosis and Mycobacterium abscessus, as well as the harmless Mycobacterium smegmatis, which was used in this research.

The scientists determined that Mycobacterial gene called lsr2 is essential for many mycobacteriophages to successfully infect Mycobacteria. Mycobacteria that carry a mutation that renders the Lsr2 protein non-functional are resistant to these phages.

Normally, Lsr2 aids in DNA replication in bacterial cells. Bacteriophages can harness this protein, however, and use it to reproduce the phage’s DNA. Thus, when Lsr2 stops working, the phage cannot replicate and it cannot manipulate bacterial cells.

In the video above, by first study author Charles Dulberger, a genetically engineered mutant phage infects Mycobacterium smegmatis. First, one phage particle (red dot at 0.42 seconds) binds to a bacterium. The phage DNA (green fluorescence) is injected into the bacterial cell (2-second mark). The bright green dots at the cells’ ends are not relevant. For a few seconds, the DNA forms a zone of phage replication, and fills the cell. Finally, the cell explodes at 6:25 seconds. (About three hours have been compressed to make this video.)

The approach used in this study can also be used to investigate other links between bacteriophages and the bacteria they infect.

“This paper focuses on just one bacterial protein,” noted co-corresponding study author Graham Hatfull, a Professor at the University of Pittsburgh. But there are many more opportunities to use this technique. “There are lots of different phages and lots of other proteins.”

Sources: University of Pittsburgh, Nature Microbiology

Carmen Leitch

Microbiology

Streptococcus pyogenes, which is often called group A Streptococcus, infects people around the world. While estimates vary, these …

6 March, 2023 Admin Leave a comment

Streptococcus pyogenes, which is often called group A Streptococcus, infects people around the world. While estimates vary, these infections could be responsible for the deaths of over half a million individuals every year. The pathogen can also cause an illness known as scarlet fever, which usually occurs in kids between the ages of 5 and 15. Scarlet fever was once a major health threat for children, and there were infection rates as high as 20 percent in the early 20th century. The disease became less of a public health concern until its recent reemergence in the UK, Hong Kong, and mainland China.

Isolates taken from patients have shown that S. pyogenes can carry resistance genes that shield it from the effects of antibiotics including tetracycline, erythromycin and clindamycin. These bacteria can also generate powerful toxins, like molecules called SSA and SpeC, known as superantigens, and an enzyme called Spd1.

While S. pyogenes infections are still rare, they can kill as many as 20 percent of people who are infected.

In 2019, a variant isolated in the UK, the so-called M1UK strep A variant, was shown to produce five times more strep A toxins compared to previous strains. The SpeA superantigen generated by this variant can short-circuit host immunity and was once known as the scarlet fever toxin. The M1UK variant also carried a few genetic mutations compared to previous strains, and one of those mutations was located close to the toxin gene. The findings have been reported in Nature Communications.

More research will be needed to know whether this variant has gotten better at moving from one person to another to cause infection.

Strep A is very rare, and the study authors noted that people should not be concerned about this novel variant at this time. Basic hygiene practices, like hand washing, can still protect us from dangerous germs like S. pyogenes. Strep A infections are spread through close contact with infected people, who may be coughing and sneezing. Other symptoms include a rash and fever.

The study authors also noted that these findings have highlighted the importance of developing a vaccine for Strep A infections.

An unrelated study reported in mBio has also revealed a different mutation that occurs in a Strep A variant that increases the production of a toxin called streptolysin O (SLO). SLO can help Strep A survive in the host, evade host immunity, and is destructive to host tissues. Variants that did not express SLO were not as virulent, noted the study authors.

Right now, scientists are working on a Strep A vaccine, as described in the video above.

Sources: Nature Communications, Griffith University, mBio

Carmen Leitch

Microbiology

Infections with many different types of bacteria including Streptococcus pneumonia, Listeria monocytogens, and Neisseria mengitidis can cause bacterial …

4 March, 2023 Admin Leave a comment

Infections with many different types of bacteria including Streptococcus pneumonia, Listeria monocytogens, and Neisseria mengitidis can cause bacterial meningitis. It’s estimated that every year over 1.2 million cases of bacterial meningitis happen around the world, and without treatment, this deadly disease is fatal to seven of ten people who are sickened by it. Even with antibiotic treatments, three of ten patients die. Survivors are left with issues like chronic headaches, seizures, loss of vision or hearing, and other neurological consequences. New research reported in Nature has revealed how bacteria are able to penetrate the meninges that surround and protect the brain to cause bacterial meningitis. The findings have shown that bacteria use neurons to evade immunity and infect the brain, and the work may aid in the creation of new therapeutics.

Right now, antibiotics can help eliminate the bacterial pathogens that cause this illness. But steroids are also needed to control the dangerous inflammation that can occur along with the infection. However, reducing inflammation also weakens the immune response, making it harder to get rid of the infection.

In this research, the scientists used Streptococcus pneumoniae and Streptococcus agalactiae bacteria, which can both cause bacterial meningitis in humans. They determined that when these bacteria get to the meninges, they release a toxin, which activates neurons in the meninges that sense pain. This pain neuron activation could explain why bacterial meningitis patients get horrible headaches, noted the researchers.

The activated pain neurons then release a signaling molecule called CGRP, which binds to a receptor called RAMP1 on the surface of immune cells called macrophages. Once CGRP binds to RAMP1 on macrophages, the immune cells are basically disabled, and they stop responding to bacterial infections like they normally would.

The link between CGRP and RAMP1 on macrophages also stops them from signaling to other immune cells, which allows the bacterial infection to not only penetrate the meninges but to spread infection.

This work was confirmed with the use of a mouse model that lacked the pain neurons that are activated by bacteria. Compared to mice with those neurons, the engineered mice had less severe brain infections when they were exposed to bacteria that cause meningitis. There were also lower levels of CGRP in the engineered mice compared to normal mice. The normal mice, however, had higher levels of bacteria in the meninges.

Additional experiments also showed that when mice were treated with drugs that block RAMP1, the severity of the bacterial infection was reduced. Mice treated with RAMP1 blockers were able to clear their infections faster too.

It may be possible to help the immune system clear cases of bacterial meningitis with medications that block either CGRP or RAMP1, potentially in conjunction with antibiotics. There are already drugs that can do this, and they are generally used to treat migraine.

Sources: Harvard Medical School, Nature

Carmen Leitch

Microbiology

Though the COVID-19 pandemic has waned, SARS-CoV-2 is still with us, and we still need diagnostic tests. Scientists …

28 February, 2023 Admin Leave a comment

Though the COVID-19 pandemic has waned, SARS-CoV-2 is still with us, and we still need diagnostic tests. Scientists have been improving those tests in several ways. Researchers are developing a test that can rapidly diagnose new COVID-19 infections within hours of exposure. A combination flu and COVID-19 test has recently been approved by the US Food and Drug Administration (FDA) and is now available to consumers for use at home. A COVID-19 home test with greater sensitivity has also been created and will hopefully reach the market soon.

Typical COVID-19 tests identify viral particles in swabs of the nostrils, throat, and/or cheeks. But those tests are best used during certain windows, and they can miss active infections when there isn’t much viral material available because a person is asymptomatic, or the infection has not yet set in and begun to replicate robustly. A totally new type of test uses a different approach, and aims to detect the immune response to the virus. The work has been published in Cell Reports Methods.

A viral infection activates the expression of a variety of immune genes, which are transcribed into mRNA molecules. The test detects certain levels of those mRNA molecules. The researchers used blood samples collected during the COVID-19 pandemic to validate their results; the test detected COVID-19 infections, even in asymptomatic people, with 98.4 percent accuracy.

More work is still needed to improve the test. For example, it uses blood samples and not nasal swabs. The scientists also need to verify that it can distinguish between different types of viral infections, like COVID-19 and the flu. But the researchers are hopeful that the diagnostic test will be available in the near future.

A combination flu and COVID-19 test is already on the market. The FDA recommends the test for anyone with symptoms of a respiratory tract infection symptoms. It’s called the Lucira COVID-19 & Flu Home test. It does not require a prescription, requires nasal swabs that can be collected by the user at home, and results are available in about 30 minutes.

While samples have to be collected by an adult, the test can be used on anyone older than 2. There is a small risk of false negatives, noted the FDA, so if respiratory infection symptoms exist and the test is negative, people may still want to follow up with their healthcare provider.

Scientists have also developed a much more sensitive test for COVID-19 that can be used at home. The work was reported in ACS Infectious Diseases.

At-home tests change color when an antibody-linked reporter molecule latches onto viral particles in a sample. But that color change is very faint when few viral particles are present. PCR-based tests are good for disease detection because only very small amounts of viral material have to be present; they are then amplified by PCR. But special equipment is needed for PCR.

This new, sensitive test has added an amplification step to a test that can be used at home. A hybridization chain reaction (HCR) boosts the signal of reporter molecules instead. The viral protein gets tagged with a DNA molecule, which can act as a scaffold that more reporter molecules can bind to. Thus, every viral particle triggers the emission of a much stronger signal.

When the sensitive test was compared to tests that are on the market, it was 2.5 times more sensitive than the best, and 100 times more sensitive than the worst. The researchers are now working to get the new test to the market.

Sources: California Institute of Technology, ACS Infectious Diseases, The Associated Press, Simons Foundation, Cell Reports Methods

Carmen Leitch

Microbiology

The Centers for Disease Control and Prevention (CDC) has issued an alert about a rise in extensively drug-resistant …

28 February, 2023 Admin Leave a comment

The Centers for Disease Control and Prevention (CDC) has issued an alert about a rise in extensively drug-resistant (XDR) Shigella infections (shigellosis). There has been a concerning increase in drug resistance among Shigella infections in the United States; they rose from zero in 2015 to 5 percent in 2022. There are few treatment options for these infections, the bacteria are easy to transmit from one person to another, and few microbes need to be transmitted for illness to occur. The microbes generally spread through the fecal-oral route, which means contaminated food and water can also cause the illness. The bacteria are also transmitted during sexual contact. The XDR strains of Shigella can also share those resistance genes with other bacteria. Therefore, the CDC is especially concerned about these infections, and is calling on health professionals to watch for cases of XDR shigellosis.

Shigella causes abdominal cramping and diarrhea that can be bloody; it may also cause fever or tenesmus, a feeling of flu bowels. Usually, these infections resolve on their own after a few days, and only supportive care, such as hydrating fluids, are needed. Antibiotics can shorten the duration of the illness, reduce the likelihood of transmission to others, and can also prevent complications.

Strains of XDR Shigella are resistant to many popular antibiotics that are usually used to treat shigellosis, including azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole (TMP-SMX), and ampicillin. Right now, there is no consensus on the best way to eliminate XDR Shigella. Strains of resistant Shigella include Shigella sonnei and Shigella flexneri.

Shigella infections tend to impact certain populations, including children between the ages of 1 and 4. International travelers, and men who have sex with men are other groups who tend to have higher than usual rates of shigellosis.

There have been 232 confirmed cases that have occured in recent years that the CDC has information about, and of those cases, 82 percent were men, 13 percent were women and 5 percent were children. While only 41 of these individuals answered questions about sexual activity, 88 percent of them reported male-to-male sexual contact.

The CDC has noted that clinicians should consider shigellosis when patients, particularly young children, international travelers, or men who have sex with men present with acute diarrhea.

A diagnosis is usually confirmed with a stool sample, particularly for patients who will receive antibiotics. Tests can also be performed to determined whether Shigella strains are susceptible to antibiotics.

Source: CDC

Carmen Leitch

Microbiology

A variety of studies have shown that when the air is drier, viral particles can linger there longer. …

25 February, 2023 Admin Leave a comment

A variety of studies have shown that when the air is drier, viral particles can linger there longer. These findings have now been confirmed in an analysis of particles of a virus that is very similar to the one that causes COVID-19, SARS-CoV-2. Although previous work has shown that relative humidity levels affect the length of time of a virus stays infectious in the air, this is the first to factor in the effect of saliva, which helps shield viral particles. The data can help explain why people tend to get more sick during winter, when humidity levels drop significantly indoors. It also stresses the importance of good ventilation systems and other mitigation efforts for preventing the spread of illness. The work has been reported in PNAS Nexus.

This study used a mammalian coronavirus that is very similar to SARS-CoV-2. Particles containing this virus remained infectious for twice as long when air was drier. These particles are normally expelled with saliva, which acts like a protective shield, particularly when humidity is low.

Although civil engineers typically design and maintain buildings so their indoor relative humidity will stay between 40 and 60 percent, the reality is a bit different, and varies widely depending on the climate of the region. The researchers suspected that these humidity levels were influencing the spread of SARS-CoV-2.

To test that theory, the investigators engineered airborne particles containing virus, with and without saliva. These were then released into large, sealed chambers with relative humidity levels of 25, 40, and 60 percent.

The saliva protected the virus at every humidity level, and at 40 and 60 percent relative humidity, half of the airborne viral particles were still infectious one hour after release. Half of the airborne particles were still infectious two hours after release at 25 percent humidity; as the relative humidity dropped, the virus was still pathogenic for much longer.

“It shows this virus can hang around for quite a while, hours even. It’s longer than a class, longer than the time you’re in a restaurant, longer than the time you take to hang out in the cafe. An occupant may come in, spread coronavirus in the air, and leave. Depending on architectural factors, then someone else could walk into that space with potent doses still hanging around,” said senior study author Mark Hernandez, a Professor of Civil and Environmental Engineering at the University of Colorado at Boulder.

The virus is probably also contaminating air for longer than it takes typical ventilation systems to eliminate it. Thus, additional mitigation strategies like filtration could reduce transmission, suggested the study authors.

“I hope this paper has an engineering impact in our buildings, for example, in schools and hospitals, so that we can minimize the infectivity of these viruses in the air,” said lead study author Marina Nieto-Caballero, PhD.

Increasing indoor humidity levels could help reduce risk for people who live in naturally arid environments, but that can be inefficient and expensive, said Hernandez. We can use strategies that we already know about instead, like opening windows, using inexpensive air filters, and increasing ventilation rates to introduce more fresh air, Hernandez added.

Sources: University of Colorado at Boulder, PNAS Nexus

Carmen Leitch

Microbiology

Gut Bugs: The Microbes Responsible for Controlling Your Body’s Temperature

25 February, 2023 Admin Leave a comment

Normal body temperature can vary from individual to individual. However, despite this variation, the average basal body temperature of humans has mysteriously dropped since the 1860s. A recent study points to the gut microbiome as a possible contributor to regulating body temperature, both in healthy individuals and during life-threatening infections.

The study, conducted by a team of researchers led by Robert Dickson, M.D., at the University of Michigan Medical School, utilized health records from patients admitted to the hospital with sepsis and conducted experiments on mice to investigate the relationship between the gut bacteria composition, temperature changes, and health outcomes.

Sepsis, the body’s response to a life-threatening infection, can cause drastic changes in body temperature, the trajectory of which is linked to mortality. Previous work has demonstrated that hospitalized patients with sepsis vary widely in their temperature responses, and this variation predicts their survival.

“There’s a reason that temperature is a vital sign,” said Kale Bongers M.D. Ph.D., a clinical instructor in the Department of Internal Medicine and lead author of the study. “It’s both easily measured and tells us important information about the body’s inflammatory and metabolic state.”

Yet the causes of this temperature variation, both in sepsis and in health, have remained unknown.

“We know that temperature response is important in sepsis because it strongly predicts who lives and who dies,” said Dickson. “But we don’t know what drives this variation and whether it can be modified to help patients.”

To try to understand the cause of this variation, the team analyzed rectal swabs from 116 patients admitted to the hospital. The patients’ gut microbiota varied widely, confirming that it is a potential source of variation.

“Arguably, our patients have more variation in their microbiota than they do in their own genetics,” said Bongers. “Any two patients are more than 99% identical in their own genomes, while they may have literally 0% overlap in their gut bacteria.”

The authors found that this variation in gut bacteria was correlated with patients’ temperature trajectories while in the hospital. In particular, common bacteria from the Firmicutes phylum were most strongly associated with increased fever response. These bacteria are common, variable across patients, and are known to produce important metabolites that enter the bloodstream and influence the body’s immune response and metabolism.

To confirm these findings under controlled conditions, the team used mouse models, comparing normal mice with genetically identical mice that lack a microbiome. Experimental sepsis caused dramatic changes in the temperature of conventional mice but had a blunted effect on the temperature response of germ-free mice. Among mice with a microbiome, variation in temperature response was strongly correlated with the same bacterial family (Lachnospiraceae) that was found in humans.

“We found that the same kind of gut bacteria explained temperature variation both in our human subjects and in our laboratory mice,” said Dickson. “This gave us confidence in the validity of our findings and gives us a target for understanding the biology behind this finding.”

Even in health, mice without a microbiome had lower basal body temperatures than conventional mice. Treating normal mice with antibiotics also reduced their body temperature.

The study highlights an underappreciated role of the gut microbiome in body temperature and could explain the reduction in basal body temperature over the past 150 years.

“While we certainly haven’t proven that changes in the microbiome explain the drop in human body temperature, we think it is a reasonable hypothesis,” said Bongers. “Human genetics haven’t meaningfully changed in the last 150 years, but changes in diet, hygiene, and antibiotics have had profound effects on our gut bacteria.”

Further research is needed to understand whether targeting the microbiome to modulate body temperature could help alter the outcome for patients with sepsis.

Reference: “The Gut Microbiome Modulates Body Temperature Both in Sepsis and Health” by Kale S. Bongers, Rishi Chanderraj, Robert J. Woods, Roderick A. McDonald, Mark D. Adame, Nicole R. Falkowski, Christopher A. Brown, Jennifer M. Baker, Katherine M. Winner, Daniel J. Fergle, Kevin J. Hinkle, Alexandra K. Standke, Kimberly C. Vendrov, Vincent B. Young, Kathleen A. Stringer, Michael W. Sjoding and Robert P. Dickson, 23 January 2023, American Journal of Respiratory and Critical Care Medicine.
DOI: 10.1164/rccm.202201-0161OC

Michigan Medicine – University of Michigan

Microbiology

Scientists have found that a gene that has been previously identified in many animals and their associated microbes …

25 February, 2023 Admin Leave a comment

Scientists have found that a gene that has been previously identified in many animals and their associated microbes can enable resistance to antimicrobial drugs. The resistance gene encodes for an enzyme called EstT, which can deactivate antibiotic drugs known as macrolides. The enzyme can disrupt the chemical ring structure of these antibiotics through hydrolysis. When the ring is broken or opened with water, the antibiotic loses both its active shape, and its target affinity, explained study leader Dr. Tony Ruzzini PhD, an assistant professor at the Western College of Veterinary Medicine (WCVM) of the University of Saskatchewan. The findings have been reported in the Proceedings of the National Academy of Sciences.

This gene can take macrolide antibiotics out of commission, and illnesses can no longer be treated effectively. Macrolides such as tylosin, tilmicosin and tildipirosin are often used to treat cattle with bovine respiratory disease or liver abscesses, and may also be used to treat other diseases in livestock and companion animals.

In this study, the researchers analyzed genes that were found within microbes that were living in watering bowls at a beef cattle feedlot in western Canada. The investigators isolated the microbes that were in the water, and compared the genes in the microbes to databases of antimicrobial resistance genes.

A bacterium called Sphingobacterium faecium WB1 was found to carry the EstT gene, which was contained within a cluster of three antibiotic resistance genes (ARGs). It was also near plasmids and retrotransposons, suggesting it can move easily from one microbe to another. EstT is commonly found in microbes in the human microbiome too.

“This gene, even though we found it in an environmental organism, it is also present in pathogens that are responsible for causing bovine respiratory disease,” noted Ruzzini.

“Our finding adds to the considerable database of ARGs, which can be crossmatched to a bacteria’s DNA to determine if the bacterium has the potential to be resistant to a particular antimicrobial,” said first study author Dr. Poonam Dhindwal PhD, a postdoctoral fellow at WCVM.

The researchers are continuing to study EstT to learn more about how it works.

“As [antimicrobial resistance] surveillance systems rely more on molecular tools for detection, our knowledge of this specific gene and its integration into those systems will help to better inform antimicrobial use,” said Ruzzini.

Sources: University of Saskatchewan, Proceedings of the National Academy of Sciences (PNAS)

Carmen Leitch

Microbiome: From Research and Innovation to Market