New U.S. rules on risky pathogen research draw mixed reviews

Food for thought! No doubt this has been a dangerous grey area for several decades of e.g. dual use!

Remember: Under Anthony Fauci so called gain of function research was funded by the US government at the Wuhan Institute of Virology (a dual use research institute) in China, where the Covid-19 coronavirus may have escaped (lab leak hypothesis). What moron ever had that great idea?

"A new U.S. policy that aims to reduce the risks arising from federally funded research with dangerous pathogens ...

Last year, in response to those concerns, President Donald Trump ordered the National Institutes of Health (NIH) and other research funding agencies to pause or review studies that potentially involved so-called dangerous gain-of-function (DGOF) research. Such experiments give pathogens new characteristics, such as the ability to more easily spread or cause death. The White House also tasked agencies with developing the new policy to stop other “high risk life sciences research.”

The 12-page policy—which broadly follows the language in Trump’s executive order—includes several departures from past U.S. attempts to govern similar work. It appears to cover all pathogens, rather than limiting regulation to a specific list, such as only those with “pandemic potential.” It requires researchers and universities to identify any study that might produce a biological agent that would “significantly endanger” people or agriculture. They must thoroughly evaluate its risks and benefits before submitting a funding proposal to the government. ...

In addition, the policy imposes an outright ban—rather than tighter review requirements—on funding for seven kinds of biological research that the policy defines as DGOF. That list of forbidden studies includes projects that could make a pathogen more transmissible, for instance, or better able to evade the human immune system. It also includes efforts to resurrect an extinct pathogen, such as the virus that caused the 1918 flu pandemic—a project completed in 2012 by a team led by one of NIH’s own scientists.

The policy also bars funding for studies in the nascent field of “mirror life”—engineered microorganisms with reversed molecular building blocks that could theoretically threaten all life on Earth. No governments have so far enacted bans on such research and the issue has divided scientists, with some calling such prohibitions premature. ..."

"... This comprehensive framework prohibits federally supported dangerous gain-of-function (DGOF) research while establishing stronger oversight for life sciences research that could pose significant risks to public health, biosecurity, or national security. The policy fulfills President Trump’s Executive Order aimed at improving the safety and security of biological research, and it ensures that taxpayer-funded research advances scientific discovery and medical innovation without exposing Americans to biological risks. ...

“Today, we are ending federal support for dangerous gain-of-function research and replacing weak oversight with clear, enforceable safeguards. ... ”Specifically, the new policy prohibits federal support for dangerous gain-of-function research conducted in the United States and abroad, establishes rigorous independent review for certain high-risk life sciences research, and restricts federal funding for research conducted in countries or institutions that lack appropriate biosafety, biosecurity, and oversight standards. At the same time, the policy preserves critical biomedical research — including the development of vaccines, therapeutics, diagnostics, and other medical countermeasures — under strong safety and security safeguards. ..."

New U.S. rules on risky pathogen research draw mixed reviews | Science | AAAS

Trump Administration Releases New Government-Wide Policy to End Dangerous High-Risk Research

Breakthrough microscope reveals real time flu virus cell invasion

Amazing stuff! What other pathogens can we now watch in action? This could be a breakthrough!

Will we soon have even better flu vaccinations?

"... On the surface of the influenza virus are two molecular "keys": hemagglutinin (HA) and neuraminidase (NA). They are the virus's lockpicks, the tools that let it slip into our cells and spread from one host to another.

The flu virus attacks much like a thief looking for unlocked doors. Its HA and NA proteins grab onto tiny molecules called sialic acids on the surface of cells. Once attached, the virus slides along the surface until the cell reshapes itself and swallows the virus inside. This process is called endocytosis.

But watching how the flu virus sneaks into cells has been difficult because standard microscopes can't capture these fast, tiny steps clearly.

In a breakthrough study, scientists from Switzerland and Japan built a new kind of "super microscope" by blending two powerful imaging tools: atomic force microscopy (AFM) and fluorescence microscopy, creating a new method called virus-view dual confocal and AFM (ViViD-AFM). This hybrid system lets researchers zoom in on living human cells with incredible detail. This offers a new real time insight into how the flu virus operates.

For the first time, researchers could actually see the nanoscale drama of influenza invading a cell. But what surprised them most was the target cell's role in this process. Instead of sitting quietly and letting the virus in, the cell seemed to fight back: stretching, shifting, and even trying to grab hold of the virus as if to control the encounter. "The infection of our body cells is like a dance between virus and cell," ...

With their new system, the team watched how single flu virus particles move across the surface of a cell under different conditions, like when specific viral proteins were blocked, when fewer binding sites were available on the cell, or when different virus types were tested. They also studied how the cell's membrane changes shape before and during the virus's entry. ..."

From the significance and abstract:

"Significance

Influenza A viruses (IAVs) continue to cause epidemics worldwide due to their high mutability. Nevertheless, the initial step of infection, viral uptake into cells, has been challenging to observe directly with conventional microscopy techniques. Here, we developed a hybrid imaging system combining atomic force microscopy and confocal microscopy with enhanced mechanical functionality and minimal invasiveness to directly visualize nanoscale dynamics of IAV and cell membranes during viral uptake into living cells. This system enables the analysis of IAV lateral diffusion resulting from IAV–membrane interactions and characteristic membrane morphological changes induced by IAV during endocytosis. Our approach offers a method to rapidly assess the impact of viral mutations on host cell entry, which is critical for understanding emerging IAV variants.

Abstract

Influenza A virus (IAV) entry into host cells begins with interactions between the viral envelope proteins hemagglutinin (HA)/neuraminidase (NA) and sialic acid moieties on the cell plasma membrane.

These interactions drive IAV’s lateral diffusion along the cell membrane and trigger membrane morphological changes required for endocytosis. However, directly visualizing these dynamic processes, which are crucial for IAV entry, has been challenging using conventional microscopy techniques.

In this study, we enabled live-cell observation of nanoscale morphological dynamics of IAV and the cell membrane by reducing the mechanical invasiveness of atomic force microscopy (AFM).

A customised cantilever with less than half the spring constant of conventional cantilevers enabled virus-view AFM imaging that preserved IAV–membrane interactions.

By combining virus-view AFM with confocal microscopy, we performed correlative morphological and fluorescence observations of IAV lateral diffusion and endocytosis in living cells.

Variations in diffusion coefficients of single virions suggested heterogeneity in sialic acid density on the cell membrane. NA inhibition decreased diffusion coefficients, while reduced sialic acid density increased them.

The timing of clathrin accumulation at virion binding sites coincided with a decrease in diffusion coefficients, a relationship that was maintained independent of NA activity or sialic acid density. As clathrin assembly progressed, ~100-nm-high membrane bulges emerged adjacent to the virus, culminating in the complete membrane envelopment of the virus at peak clathrin accumulation.

Our virus-view AFM will deepen our understanding of various virus–cell interactions, facilitate the evaluation of drug effects and promote future translational research."

Breakthrough microscope reveals real time flu virus cell invasion

How influenza viruses enter our cells (original news release) "For the first time, researchers have observed live and in high resolution how influenza viruses infect living cells. This was possible thanks to a new microscopy technique, which could now help to develop antiviral therapies in a more targeted manner. "

Enhanced visualization of influenza A virus entry into living cells using virus-view atomic force microscopy (open access)

Fig. 4 Membrane bulges cover virus particles during IAV CME. 

The African clawed Frog That Unleashed the World’s Most Lethal Pathogen Batrachochytrium dendrobatidis on amphibians

Recommendable!

Scientists discover how cells use a secret weapon to fight off some pathogens

Amazing stuff! Did you take your vitamin supplement today?

"Key takeaways

• ... research shows that mitochondria detect invading pathogen Toxoplasma gondii and ramp up competition for vitamin B9, also known as folate, depriving it of the nourishment it needs to grow.
• This new discovery came about when a researcher noticed that the amount of mitochondrial DNA in a mitochondrion increased during an infection.
• The new discovery raises the possibility that a vitamin regimen could rewire mitochondrial metabolism to make it even more effective at preventing infections, such as toxoplasmosis, in people.

...

mitochondria starve pathogens by competing with them for vitamin B9 (folate) to prevent infection. The researchers found that the folate used by mitochondria as part of their normal metabolism reduced the amount of folate available to a specific parasite, Toxoplasma gondii, which subsequently grew more slowly. ..."

From the editor's summary and abstract:

"Editor’s summary

Mitochondria consume nutrients that are also needed by invading pathogens. Whether cells exploit this overlap for host defense has been unclear. Medeiros et al. found that cells harness mitochondrial metabolism to restrict access of the intracellular parasite Toxoplasma gondii to the essential B vitamin folate (see the Perspective by Suomalainen and Nikkanen). When host cells detect intracellular parasite effectors, they activate the integrated stress response and its key effector, ATF4. ATF4 induces one-carbon metabolism processes in host mitochondria that use folate. Because Toxoplasma requires folate to generate thymidine for DNA synthesis, ATF4 activation restricts parasite replication. Thus, infected cells can weaponize mitochondrial metabolism to defend against pathogens. ...

Structured Abstract

INTRODUCTION

Mitochondria ... also use and consume many nutrients that invading pathogens rely on. ...

RATIONALE

... We focused on the replication of mitochondrial DNA (mtDNA), which requires nutrients including those that maintain one-carbon metabolism processes required for nucleotide biosynthesis. We found that infection with the intracellular parasite Toxoplasma gondii increased mtDNA copy number. This response was independent of mitochondrial biogenesis but required activating transcription factor 4 (ATF4), which was activated through the integrated stress response (ISR) kinase HRI in response to parasite effector–induced mitochondrial stress.

RESULTS

Having identified that Toxoplasma infection led to an increase in mtDNA in an ATF4-dependent manner, we next investigated the underlying mechanism. During infection, ATF4 induced the mitochondrial one-carbon enzymes MTHFD2 and SHMT2, which use folate to provide carbon units for biosynthetic pathways, such as nucleotide synthesis. Both ATF4 and MTHFD2 were required for the increase in mtDNA and for restricting parasite growth. We pinpointed this restriction to competition for folate, an essential cofactor that Toxoplasma requires to produce deoxythymidine monophosphate (dTMP) and to proliferate.

Disrupting mitochondrial one-carbon metabolism—through ATF4 loss or methotrexate treatment—led to increased parasite dTMP synthesis and replication. In vivo, preventing ATF4 activation through pharmacological inhibition of the ISR similarly elevated parasite burden.

CONCLUSION

We discovered a host defense strategy rooted in metabolic competition between mitochondria and an intracellular pathogen. This defense was mediated by the ISR effector ATF4, which was activated in response to the detection of parasite effector–induced mitochondrial stress. ATF4 enhanced mitochondrial one-carbon metabolism, thereby depriving Toxoplasma gondii of host folate(s) and limiting its ability to synthesize dTMP and proliferate.

Thus, mitochondria execute a noncanonical metabolic defense against an intracellular pathogen. We propose that these organelles are positioned to compete with other intracellular pathogens for nutrients, such as folate, that are essential for their replication."

Scientists discover how cells use a secret weapon to fight off some pathogens | UCLA "Mitochondria use folate in such quantities that invading Toxoplasma gondii grows more slowly"

Mitochondria protect against an intracellular pathogen by restricting access to folate

Host cells weaponize mitochondrial metabolism.

One major Flu Strain Has Likely Gone Extinct Since 2020

Good news! They come and go! 

OMG, my next flu shot in September 2025 will not contain this strain anymore? A new strain will be added? How will my body respond? Just kidding!

Contrast this with the daily reports/alarmism of new Avian flu, Covid-19 strains and so on as if we are doomed.

"“Flu viruses spread every year and cause seasonal outbreaks. But one type, called influenza B Yamagata, may have completely disappeared…

This likely happened because COVID-19 precautions — such as social distancing, masks, and travel restrictions — sharply reduced social contact. With fewer opportunities to spread from person to person, B Yamagata couldn’t sustain transmission and eventually died out.

Regulatory health agencies like the WHO, European Medicines Agency, and US CDC have recommended removing it from flu vaccines. This could allow room for other strains to be included in seasonal flu vaccines, improving overall vaccine effectiveness.”"

A Flu Strain Has Likely Gone Extinct Since 2020 - Human Progress

Metagenomic sequencing test proves effective in diagnosing almost any kind of pathogen

Good news! A good diagnosis precedes a successful treatment!

"... It uses a powerful genomic sequencing technique, called metagenomic next-generation sequencing (mNGS).

Rather than looking for one type of pathogen at a time, mNGS analyzes all the nucleic acids, RNA and DNA, that are present in a sample. ...

The test has now been performed on thousands of patients with unexplained neurological symptoms, both at UCSF and other hospitals across the country.

In a paper ... the team demonstrated that the mNGS test correctly identified 86% of neurological infections. ...

In a companion study ... the team also used mNGS to identify pathogens in respiratory fluid that can cause pneumonia, and automated it to get results faster. ..."

From the abstract (1):

"Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples (n = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples (P < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection."

From the abstract (2):

"Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in <24 h. The mNGS assay achieved mean limits of detection of 543 copies/mL, viral load quantification with 100% linearity, and 93.6% sensitivity, 93.8% specificity, and 93.7% accuracy compared to gold-standard clinical multiplex RT-PCR testing. Performance increased to 97.9% overall predictive agreement after discrepancy testing and clinical adjudication, which was superior to that of RT-PCR (95.0% agreement). To enable discovery of novel, sequence-divergent human viruses with pandemic potential, de novo assembly and translated nucleotide algorithms were incorporated into the automated SURPI+ computational pipeline used by the mNGS assay for pathogen detection. Using in silico analysis, we showed that after removal of all human viral sequences from the reference database, 70 (100%) of 70 representative human viral pathogens could still be identified based on homology to related animal or plant viruses. Our assay, which was granted breakthrough device designation from the US Food and Drug Administration (FDA) in August of 2023, demonstrates the feasibility of routine mNGS testing in clinical and public health laboratories, thus facilitating a robust and rapid response to the next viral pandemic."

Metagenomic sequencing test proves effective in diagnosing almost any kind of pathogen "A genomic test developed at UC San Francisco to rapidly detect almost any kind of pathogen—virus, bacteria, fungus or parasite—has proved successful after a decade of use."

1 Genomic Test Can Diagnose Nearly Any Infection (original news release) "Next-generation metagenomic sequencing test developed at UCSF proves its effectiveness in quickly diagnosing almost any kind of pathogen."

Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections (open access)

Laboratory validation of a clinical metagenomic next-generation sequencing assay for respiratory virus detection and discovery (open access)

Fig. 1: Schematic of the mNGS assay workflow.

Gene expression levels of the enzyme, OLAH, is critical in determining disease severity

Good news! Amazing stuff!

"... Scientists have identified a gene associated with whether patients hospitalised with respiratory viral infections experience mild disease or life-threatening complications.

According to the new study published in Cell, expression levels of the gene, OLAH, is critical in determining disease severity. ..."

From the highlights and abstract:

"Highlights

• Fatal H7N9 flu patients express high OLAH levels throughout hospitalization

• High OLAH levels are detected in severe H1N1, COVID-19, RSV, and MIS-C patients

• Olah−/− mice are protected from lethal influenza disease and excessive inflammation

• Olah expression in macrophages drives viral infection and an inflammatory milieu

Summary

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death. Recovered patients had low OLAH expression throughout hospitalization. High OLAH levels were also detected in patients hospitalized with life-threatening seasonal influenza, COVID-19, respiratory syncytial virus (RSV), and multisystem inflammatory syndrome in children (MIS-C) but not during mild disease. In olah−/− mice, lethal influenza infection led to survival and mild disease as well as reduced lung viral loads, tissue damage, infection-driven pulmonary cell infiltration, and inflammation. This was underpinned by differential lipid droplet dynamics as well as reduced viral replication and virus-induced inflammation in macrophages. Supplementation of oleic acid, the main product of OLAH, increased influenza replication in macrophages and their inflammatory potential. Our findings define how the expression of OLAH drives life-threatening viral disease."

Gene linked to life-threatening respiratory viral infections

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases

Graphical abstract

Microbe-wave: radiation-resistant microbes found in microwave ovens

Sounds appetizing? I bet this is not the first study on microwave ovens with such or similar results since microwave ovens for consumers became affordable in the 1960s.

I suppose, the microbes growing and living in our microwave ovens are not particularly dangerous. No hazmat signs necessary yet. 😊

"The microbiomes in some microwaves are similar to those found on solar panels. The authors propose this is due to constant thermal shock, electromagnetic radiation, and desiccation (extreme drying) selecting for highly resistant bacteria. ..."

From the abstract:

"Microwaves have become an essential part of the modern kitchen, but their potential as a reservoir for bacterial colonization and the microbial composition within them remain largely unexplored. In this study, we investigated the bacterial communities in microwave ovens and compared the microbial composition of domestic microwaves, microwaves used in shared large spaces, and laboratory microwaves, using next-generation sequencing and culturing techniques. The microwave oven bacterial population was dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, similar to the bacterial composition of human skin. Comparison with other environments revealed that the bacterial composition of domestic microwaves was similar to that of kitchen surfaces, whereas laboratory microwaves had a higher abundance of taxa known for their ability to withstand microwave radiation, high temperatures and desiccation. These results suggest that different selective pressures, such as human contact, nutrient availability and radiation levels, may explain the differences observed between domestic and laboratory microwaves. Overall, this study provides valuable insights into microwave ovens bacterial communities and their potential biotechnological applications."

Microbe-wave: radiation-resistant microbes in microwaves

The microwave bacteriome: biodiversity of domestic and laboratory microwave ovens (open access)

Figure 1. Main bacterial genera isolated from domestic, domestic-shared and laboratory microwaves.

Do not attach to your microwave yet!

Key process discovered in migraines with aura

Good news! Hopefully less suffering in the future!

"A team of Danish and US scientists has uncovered a new signalling pathway in the brain, which is linked to migraine attacks with auras – the sensory disturbances like flashing lights in vision or tingling in limbs.

The study, which was done mostly on mice, helps to explain the still poorly understood processes that trigger migraines.

The researchers found cerebrospinal fluid moves aura-causing proteins in one part of the brain to pain receptors in the nervous system, becoming the source of the sharp migraine headache. ..."

From the editor's summary and abstract:

"Editor’s summary

The pathophysiology of migraine remains to be fully elucidated. Cortical spreading depression (CSD), a wave of suppression of brain activity, has been hypothesized to play a main role in triggering headache. However, the mechanism remains elusive. Kaag Rasmussen et al. used rodent models to show that CSD could induce alterations in cerebrospinal fluid proteome, with increased expression of proteins able to activate the trigeminal nerve (see the Perspective by Russo and Iliff). These proteins could reach and activate the trigeminal nerve, thus triggering headache, through a previously unrecognized zone of the trigeminal ganglion lacking epineural sheath. These results identify a route of communication between the central and peripheral nervous systems that is potentially involved in triggering migraine. ...

Abstract

Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and trigeminal cells. After CSD, ~11% of the CSF proteome is altered, with up-regulation of proteins that directly activate receptors in the trigeminal ganglion. CSF collected from animals exposed to CSD activates trigeminal neurons in naïve mice in part by CSF-borne calcitonin gene–related peptide (CGRP). We identify a communication pathway between the central and peripheral nervous system that might explain the relationship between migrainous aura and headache."

Key process discovered in migraines with aura

A new path to migraine (no public access) Cerebrospinal fluid influx directly activates trigeminal neurons in a migraine model

Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model (no public access)

Newly discovered virus kills dormant bacteria in superbug breakthrough

Good news!

"... In hostile environments – such as when they’re exposed to antibiotics – bacteria can go into a form of hibernation, where they stop growing and dividing until things calm down. This makes it difficult to fully wipe them out and contributes to the growing problem of antibiotic resistance, which threatens to eventually make even basic infections deadly. ...

Scientists at ETH Zurich hypothesized that there must be some [bacteriophage] species that can attack bacteria in this dormant state. Now, after years of searching, they’ve identified just such a phage, which they’ve named Paride. The team found that Paride was able to infect the bacteria species Pseudomonas aeruginosa, which is responsible for a range of common infections like pneumonia and UTIs, and is increasingly becoming drug-resistant. ..."

"In brief

• For the first time, ETH Zurich researchers have isolated a bacteriophage from rotting plant material that can attack and kill bacteria in a dormant state.
• How the phage manages this is still unclear.
• Combination therapy with this phage and an antibiotic eradicates many dormant germs in pure culture and in the mouse model.

In nature, most bacteria live on the bare minimum. If they experience nutrient deficiency or stress, they shut down their metabolism in a controlled manner and go into a resting state. In this stand-​by mode, certain metabolic processes still take place that enable the microbes to perceive their environment and react to stimuli, but growth and division are suspended. ..."

From the abstract:

"Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates (“hibernation”). However, a newly isolated Pseudomonas aeruginosa phage, named Paride, can directly replicate and induce the lysis of deep-dormant hosts. While non-growing bacteria are notoriously tolerant to antibiotic drugs, the combination with Paride enables the carbapenem meropenem to eradicate deep-dormant cultures in vitro and to reduce a resilient bacterial infection of a tissue cage implant in mice. Our work might inspire new treatments for persistent bacterial infections and, more broadly, highlights two viral strategies to infect dormant bacteria (hibernation and direct replication) that will guide future studies on phage-host interactions."

Newly discovered virus kills "sleeping" bacteria in superbug breakthrough

A virus that kills sleepers (ETH Zurich) ETH Zurich researchers have found a virus that kills dormant bacteria. This rare discovery could help to combat germs that can’t be treated with antibiotics alone.

Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication (open access)

The paride phage (purple) is one of the few phages to attack dormant bacteria. 

Fig. 1: Most bacteriophages cannot replicate on deep-dormant E. coli or P. aeruginosa.

Study reveals how some bacterial infections become chronic

Good news!

"... A new study ... sheds light on the biological mechanisms that enable another kind of Salmonella to evade the immune system and cause long-term infections. The team focused on the “nontyphoidal” forms of Salmonella, which cause food-borne illness and, like the typhoidal form, can linger in the body long after the initial infection. By examining the genomes of bacteria collected from hundreds of people with persistent Salmonella infections, they discovered genetic mutations that both reduce the bacteria’s “virulence,” or ability to infect, and dampen the host’s immune responses, creating a kind of molecular camouflage that shields the bacteria from the immune system’s gaze. This insight could one day lead to new diagnostic approaches or treatments that prevent these infections from becoming chronic.  ...
they found that while most people cleared the infection after a week or so without treatment, roughly 2.2 percent of the cases became persistent infections that lingered for months to years. ...
They confirmed that most of the ​​cases were due to chronic infection by the same strain, rather than reinfection by different strains of the same bacteria. After analyzing the genomes of Salmonella in patient samples at various time points, the team highlighted mutations in two genes, barA and sirA, that arose in the bacteria repeatedly during chronic infection. ...
The mutated genes had different misspellings in different patients, suggesting that the bacteria evolve independently to lower the host immune response. ..."

From the highlights and abstract:

"Highlights

• Salmonella global regulators are frequently mutated during persistent human infection

• The barA/sirA virulence regulatory pathway was most frequently mutated

• barA/sirA mutants were less virulent and elicited a weakened host immune response

• barA/sirA mutants colonized mice and were shed during persistent salmonellosis

Summary

Several bacterial pathogens, including Salmonella enterica, can cause persistent infections in humans by mechanisms that are poorly understood. By comparing genomes of isolates longitudinally collected from 256 prolonged salmonellosis patients, we identified repeated mutations in global regulators, including the barA/sirA two-component regulatory system, across multiple patients and Salmonella serovars. Comparative RNA-seq analysis revealed that distinct mutations in barA/sirA led to diminished expression of Salmonella pathogenicity islands 1 and 4 genes, which are required for Salmonella invasion and enteritis. Moreover, barA/sirA mutants were attenuated in an acute salmonellosis mouse model and induced weaker transcription of host immune responses. In contrast, in a persistent infection mouse model, these mutants exhibited long-term colonization and prolonged shedding. Taken together, these findings suggest that selection of mutations in global virulence regulators facilitates persistent Salmonella infection in humans, by attenuating Salmonella virulence and inducing a weaker host inflammatory response."

Study reveals how some bacterial infections become chronic | Broad Institute Scientists uncover mutations that allow Salmonella to fly under the immune system’s radar for years

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway (no public access)

Graphical abstract

Syphilis-like diseases were already widespread in America before the arrival of Columbus, new study finds

So were the conquistadors actually infected by indigenous women not vice versa? (Caution: Facetious question)

"Researchers at the Universities of Basel and Zurich have discovered the genetic material of the pathogen Treponema pallidum in the bones of people who died in Brazil 2,000 years ago. This is the oldest verified discovery of this pathogen thus far, and it proves that humans were suffering from diseases akin to syphilis—known as treponematoses—long before Columbus's discovery of America. ...

The researchers used dentists' drilling tools to remove minuscule samples of bone under sterile conditions. From those samples they isolated prehistoric genetic material (ancient DNA) belonging to the syphilis pathogen. Their study demonstrates that all the bacterial genomes that have been investigated can be attributed to the Treponema pallidum endemicum strain—that is, the pathogen that leads to bejel. ...

Intense debates are still ongoing today among specialists and medical historians concerning whether Christopher Columbus's sailors and soldiers brought sexually transmitted syphilis from the New World to the Old upon their return in 1492. The illness spread rapidly from the end of the 15th century onwards, particularly in harbor towns. ...

The DNA comparison also allows the date of the Treponema pallidum family's emergence to be deduced. The team's investigations show that these pathogens arose at some point between 12,000 and 550 BCE. The history of these pathogens therefore stretches much further back than previously assumed. ..."

From the abstract:

"The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus’ expeditions. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses."

Syphilis-like diseases were already widespread in America before the arrival of Columbus, new study finds

Syphilis-like diseases were already widespread in America before the arrival of Columbus (University of Basel)

Redefining the treponemal history through pre-Columbian genomes from Brazil (open access)

Professor Verena Schünemann isolates ancient DNA in the laboratory. 

Fig. 1: The archaeological site and the T. pallidum-positive samples that yielded the reconstructed genomes.

Laboratory-acquired infections and pathogen escapes worldwide between 2000 and 2021

Maybe lab leaks are not so rare as want to believe! These events seem to be rare, but they could also be underreported.

There is a high probability that the SARS-CoV-2/Covid-19 escaped from a lab possibly the Wuhan Institute of Virology.

From the abstract:

"Laboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021. We identified LAIs in 309 individuals in 94 reports for 51 pathogens. Eight fatalities (2·6% of all LAIs) were caused by infection with Neisseria meningitidis (n=3, 37·5%), Yersinia pestis (n=2, 25%), Salmonella enterica serotype Typhimurium (S Typhimurium; n=1, 12·5%), or Ebola virus (n=1, 12·5%) or were due to bovine spongiform encephalopathy (n=1, 12·5%). The top five LAI pathogens were S Typhimurium (n=154, 49·8%), Salmonella enteritidis (n=21, 6·8%), vaccinia virus (n=13, 4·2%), Brucella spp (n=12, 3·9%), and Brucella melitensis (n=11, 3·6%). 16 APELS were reported, including those for Bacillus anthracis, SARS-CoV, and poliovirus (n=3 each, 18·8%); Brucella spp and foot and mouth disease virus (n=2 each, 12·5%); and variola virus, Burkholderia pseudomallei, and influenza virus H5N1 (n=1 each, 6·3%). Continual improvement in LAI and APELS management via their root cause analysis and thorough investigation of such incidents is essential to prevent future occurrences. The results are biased due to the reliance on publicly available information, which emphasises the need for formalised global LAIs and APELS reporting to better understand the frequency of and circumstances surrounding these incidents."

Laboratory-acquired infections and pathogen escapes worldwide between 2000 and 2021: a scoping review - The Lancet Microbe (open access)

Credits: Die unterschätzte Gefahr

Figure 1 Laboratory-acquired infection case reports, including causal pathogens for each geographical region for the period from 2000 to 2021. Note that in 1 instance the geographic location of the LAI case was not stated.

Could the next pandemic come from pets? Really!

More alarmism and hysteria spread by the AAAS (American Association for the Advancement of Science)! The AAAS is irresponsible and reckless! And the AAAS blames climate change!

Humans have domesticated animals for about 15,000 years. If there was such a danger from zoonoses we would be all dead a long time ago!

"As the COVID-19 pandemic made painfully clear, diseases that spillover from animals to humans [???]can cause devastating outbreaks. Evaluating which animals are likely reservoirs for potential pathogens and studying the nature of the diseases they carry is understandably a priority for epidemiological research. But researchers may not need to trek deep into jungles or go spelunking to find the next zoonotic virus—it may already be lurking in our homes or backyards, inside our favorite furry and feathered friends. ..." (Source)

From the abstract:

"The spillover of human infectious diseases from animal reservoirs is now well appreciated [???]. However, societal and climate-related changes [???] are affecting the dynamics of such interfaces. In addition to the disruption of traditional wildlife habitats, in part because of climate change [???] and human demographics and behavior, there is an increasing zoonotic disease risk from companion animals. This includes such factors as the awareness of animals kept as domestic pets and increasing populations of free-ranging animals in peri-domestic environments. This review presents background and commentary focusing on companion and peri-domestic animals as disease risk for humans, taking into account the human-animal interface and population dynamics between the animals themselves."

Backyard zoonoses: The roles of companion animals and peri-domestic wildlife | Science Translational Medicine (open access)

Fig. 1. Pathways for zoonotic spillovers between and via (peri-)domestic species.

Germicidal UV lights could be producing indoor air pollutants, study finds

Life is full of trade offs! What is worse?

From the abstract:

"One strategy for mitigating the indoor transmission of airborne pathogens, including the SARS-CoV-2 virus, is irradiation by germicidal UV light (GUV). A particularly promising approach is 222 nm light from KrCl excimer lamps (GUV222); this inactivates airborne pathogens and is thought to be relatively safe for human skin and eye exposure. However, the impact of GUV222 on the composition of indoor air has received little experimental study. Here, we conduct laboratory experiments in a 150 L Teflon chamber to examine the formation of secondary species by GUV222. We show that GUV222 generates ozone (O3) and hydroxyl radicals (OH), both of which can react with volatile organic compounds to form oxidized volatile organic compounds and secondary organic aerosol particles. Results are consistent with a box model based on the known photochemistry. We use this model to simulate GUV222 irradiation under more realistic indoor air scenarios and demonstrate that under some conditions, GUV222 irradiation can lead to levels of O3, OH, and secondary organic products that are substantially elevated relative to normal indoor conditions. The results suggest that GUV222 should be used at low intensities and in concert with ventilation, decreasing levels of airborne pathogens while mitigating the formation of air pollutants."

Germicidal UV lights could be producing indoor air pollutants, study finds | MIT News | Massachusetts Institute of Technology While useful for killing pathogens including SARS-CoV-2, the lights may cause unwanted chemical reactions and should be used with ventilation, researchers say.

Indoor Air Quality Implications of Germicidal 222 nm Light (open access)

Scientists develop tools for early detection of SARS-CoV-2 variants in wastewater | Scripps Research

Good news! Don't we all like sewage and wastewater! It can tell so much about us! 😄

"Now, scientists ... reported that with just two teaspoons [???] of raw sewage, they can accurately determine the genetic mixture of SARS-CoV-2 variants present within a population and identify new variants of concern up to 14 days before traditional clinical testing. In San Diego wastewater, the group detected the Omicron variant 11 days before it was first reported clinically. ..."

From the abstract:

"... SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission."

Scientists develop tools for early detection of SARS-CoV-2 variants in wastewater | Scripps Research New tools developed at Scripps Research and UC San Diego are helping public health officials around the world get vital information about pathogen variants from wastewater.

Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission (probably no public access, but preprint is available)

Ancient teeth reveal Black Death began in Kyrgyzstan, researchers say

Amazing stuff!

Molecules found in mucus can thwart fungal infection

Amazing stuff! Could be a breakthrough!

"... researchers have now identified components of mucus that can interact with Candida albicans and prevent it from causing infection. These molecules, known as glycans, are a major constituent of mucins, the gel-forming polymers that make up mucus.

Mucins contain many different glycans, which are complex sugar molecules. A growing body of research suggests that glycans can be specialized to help tame specific pathogens — not only Candida albicans but also other pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus ...

“The picture that is emerging is that mucus displays an extensive small-molecule library with lots of virulence inhibitors against all sorts of problematic pathogens, ready to be discovered and leveraged,” ..."

From the abstract:

"Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important human fungal pathogen. However, the molecular motifs in mucins that inhibit filamentation remain unclear despite their potential for therapeutic interventions. Here, we determined that mucins display an abundance of virulence-attenuating molecules in the form of mucin O-glycans. We isolated and cataloged >100 mucin O-glycans from three major mucosal surfaces and established that they suppress filamentation and related phenotypes relevant to infection, including surface adhesion, biofilm formation and cross-kingdom competition between C. albicans and the bacterium Pseudomonas aeruginosa. Using synthetic O-glycans, we identified three structures (core 1, core 1 + fucose and core 2 + galactose) that are sufficient to inhibit filamentation with potency comparable to the complex O-glycan pool. Overall, this work identifies mucin O-glycans as host molecules with untapped therapeutic potential to manage fungal pathogens."

Molecules found in mucus can thwart fungal infection | MIT News | Massachusetts Institute of Technology Harnessing the strength of these specialized sugar molecules could help researchers develop new antifungal drugs.

Mucin O-glycans are natural inhibitors of Candida albicans pathogenicity (no public access)

The more infectious form of the yeast Candida albicans is a long filament (left). MIT researchers have shown that when the yeast is grown in the presence of mucin glycans, it remains in its round, harmless form (right).

Delayed T cell Response Allows Tuberculosis to Gain Foothold in Monkeys

Amazing stuff! Why does the immune system respond so slow to an infection with TB?

"Tuberculosis kills about 1.5 million people worldwide each year. Among infectious diseases, it’s currently second only to COVID-19 as a cause of death. ...
there are many unanswered questions about the infection, including why it can linger in the body for months or years. Now, in a study conducted on monkeys ... researchers find that a key subset of infection-fighting immune cells only become fully active three months after the body first encounters Mtb, with a second subset of these cells emerging five months postinfection. The results suggest that a delayed adaptive immune response might be crucial to Mtb’s ability to establish a foothold in a host.  ...
“That [the] TB immune response is unusual compared to other pathogens had been known for years, but people still don’t really understand why,” ...
Researchers have found that Mtb is equipped with an arsenal of tools that allow it to escape the immune response, often leading to latent TB with the formation of secondary granulomas that consist of infected macrophages surrounded by immune cells “guards.” The bacteria within those structures sometimes become reactivated months or years later if the immune system weakens due to immunosuppressive therapies or disease. ..."

From the abstract:

"Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. Here, we identify and compare the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differ in transcription-factor expression within adaptive lymphocytes, with those at 12 weeks showing higher frequencies of CD8+T-bet+ T cells, while CD4+T-bet+ T cells increase at 20 weeks post-infection. The appearance of T-bet+ adaptive T cells at 12 and 20 weeks is coincident with a reduction in bacterial burden, suggesting their critical role in Mtb control. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+ T cells would enhance mycobacterial control."

Delayed T cell Response Allows Tuberculosis to Gain Foothold in Monkeys | The Scientist Magazine® The results could help guide the design of new vaccines for the disease.

T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques (open access)

Desktop air curtain could block viral spread in hospitals

Air curtains to block pathogens in hospitals? Sounds interesting, but is it practical?

"... To protect them from exposure to infections in such scenarios, a team at Nagoya University in Japan has developed a desktop air curtain system (DACS) that blocks emitted aerosol particles and prevents potential spread of viruses such as SARS-CoV-2.

The DACS contains a generator at the top that produces a steady airflow, which is then guided to a suction port at the bottom of the device, effectively creating a smooth curtain of air. ..."

Desktop air curtain could block viral spread in hospitals – Physics World