Tag Archives: Molecular Microbiology

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

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.

Image credit: Pixabay

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

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

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.

Colorized scanning electron micrograph of Group A Streptococcus (Streptococcus pyogenes) bacteria (blue) and a human neutrophil (purple). Credit: NIAID

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

In recent years, we have learned a lot about the crucial role gut microbes play in our health …

In recent years, we have learned a lot about the crucial role gut microbes play in our health and well being. The extent of their influence can be surprising at times. Research has shown that gut microbes can impact the repair of tissue damage by fueling the production of a type of immune cell called Tregs, or regulatory T cells. These cells reside in various tissues and help regulate inflammation and immunity in different organs. But new work has shown that Tregs can also move around the body and respond when they are called to help fix injuries and tissue damage, such as in the muscles and liver. The findings, which used a mouse model and still have to be confirmed in humans, have been reported in the journal Immunity.

Image credit: Pixabay

There are Tregs that reside in the colon, and these cells are known to play an important role in the maintenance of gut health. The immune system in the gut has to protect us from infection while also ignoring the harmless or beneficial microbes in the gut microbiome. Gut microbes have also been known to affect Treg production. But colonic Tregs were thought to stay in the gut. In this study, the investigators found colonic Tregs among muscle cells.

First study author Bola Hanna, a research fellow in immunology at Harvard Medical School (HMS) noticed cells that looked like gut-derived Tregs among muscle tissue. The researchers wanted to known more about these mysterious cells. First, they confirmed the identity of the Tregs by analyzing gene expression and molecular characteristics. This indicated that these cells were just like colonic Tregs. Next, the investigators tagged those cells and watched as they moved around the bodies of a mouse model. The researchers assessed the antigens on these cells as well, confirming that they were equivalent to Tregs from the gut.

When a mouse model was created to lack these Tregs, and was then subjected to muscle injury, the mice had high levels of inflammation and difficulty healing. When healing did happen, it was accompanied by scarring.

In another experiment, mice were given antibiotics to reduce the levels of gut microbes. Once again, when muscle injury occurred, it took longer to heal. But if the gut microbiome was restored, normal healing commenced.

The colonic Tregs are promoting healing in muscles by reducing the levels of an inflammatory molecule called IL-17.

The investigators also found evidence of gut Tregs in different organs including the kidneys, liver, and spleen. In a mouse model of fatty liver disease, there were unusually high levels of colonic Tregs compared to healthy mice, suggesting that Tregs are influencing inflammation in a variety of tissues.

In the mouse model of fatty liver disease, symptoms got worse when the mice lacked Tregs, which also seems to confirm that colonic Tregs are playing an important role in countering the effects of inflammation due to fatty liver disease.

“Our observations indicate that gut microbes drive the production of a class of regulatory T cells that are constantly exiting the gut and act as sentries that sense damage at distant sites in the body and then act as emissaries to repair that damage,” explained senior study author Diane Mathis, a professor of immunology in the Blavatnik Institute at HMS. This work may also help scientists create therapies for fatty liver disease.

Sources: Harvard Medical School, Immunity

Carmen Leitch

The SARS-CoV-2 virus and the illness it causes, COVID-19, have made an indelible mark on our lives. It …

The SARS-CoV-2 virus and the illness it causes, COVID-19, have made an indelible mark on our lives. It seems that is also true in more ways than one; new research has shown that when the virus infects cells, portions of the viral genome integrate into the genome of host cells in a phenomenon known as reverse transcription. While this is a relatively rare even for SARS-CoV-2, so many people have been infected with the virus that integration has probably happened many times. Scientists have now used several techniques to show that SARS-CoV-2 can integrate into a host cell genome, and the findings have been reported in the journal Viruses. This study is confirmation of previous work reported in the Proceedings of the National Academy of Sciences in 2021.

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

This research may help explain why some people continue to test positive for the virus long after their infection has subsided and they have recovered. In reverse transcription, RNA molecules, in this case from SARS-CoV-2, are transcribed into cDNA, a flip of the typical process in which active genes are transcribed into RNA molecules. Those reverse-transcribed cDNA molecules are then stitched into the host cell genome. If some of those cells are captured during a COVID-19 test, PCR would recognize and amplify the viral DNA in the host cell, causing a positive test result.

This study has also shown that simply inserting viral RNA into cells is not enough to cause genomic integration, so it seems unlikely based on the evidence we have now that mRNA from the COVID-19 vaccines would cause integration into cells’ DNA.

“This paper puts our data on a very firm footing. Hopefully, it will clarify some of the issues raised in the discussion that followed the first paper, and provide some reassurance to people who were worried about the implications for the vaccine,” said corresponding study author Rudolf Jaenisch, a founding member of the Whitehead Institute.

Since the integration of the SARS-CoV-2 genome into cells’ DNA is unusual, the researchers had to use a very sensitive method called digital PCR, which detects very specific genetic sequences, to identify instances in which viral RNA had been integrated into the genome of a cell.

The digital PCR results found viral RNA that had been reverse-transcribed to cDNA in about 4 to 20 of every 1,000 cells, but this includes all molecules of the sort, whether they ended up being integrated into a genome or not. Thus, the researchers suggested that viral integration is even more rare than that.

Whole genome sequencing can be used to show when that integration also occurred, because those events are typically accompanied by a reverse transcription complex called LINE1. The LINE1 sequences act as an indicator of integration. However, WGS is usually only used on a handful of cells, so when other investigators looked for those sequences, they could not usually be found.

“Because the human cell genome coverage by whole genome sequencing is very limited, you would need to run the sequencing experiment many times in order to have a good chance of detecting one viral genome copy,” explained postdoctoral researcher and first study author Liguo Zhang.

In this study, the researchers created cells that would overexpress LINE1, and make viral integration more common artificially. This time, the digital PCR showed that viral cDNA appeared in fourteen to twenty of every 1,000 cells, and WGS identified instances of integration along with LINE1. Further work with a tool called TagMap confirmed viral integration without overexpressing LINE1.

“This is unambiguous proof of viral genomic integration,” Zhang said. When this approach was repeated with cells that were treated with SARS-CoV-2 vaccine, there was no evidence of integration.

“We need to do further testing, but our results are consistent with vaccine RNA not integrating,” Jaenisch said.

Sources: Whitehead Institute for Biomedical Research, Viruses

Carmen Leitch

Rheumatoid arthritis (RA)  is a complex, chronic inflammatory disease that is thought to affect about one percent of …

Rheumatoid arthritis (RA)  is a complex, chronic inflammatory disease that is thought to affect about one percent of the world’s population. RA happens when a person’s own antibodies attack joint tissue, causing painful swelling, stiffness, and redness. Some research has suggested that there is a link between RA and gum disease.

Image credit: Pixabay

Gum disease is estimated to affect up to 47 percent of adults, and in the disorder, oral microbes can move to the blood after the gums start to bleed. An increase in disease activity has been observed in RA patients who also have gum disease. Gum disease has been shown to be more common in RA patients who carry a certain type of antibodies, called anti-citrullinated protein antibodies (ACPAs), though ACPAs are often found in the blood of individuals with RA. The presence of ACPAs can often predate the diagnosis of RA by a few years.

A new study investigated the connections between these observations. In this work, the researchers collected blood samples from a small group of ten people with RA, five with and five without gum disease. These samples were collected every week for one year, and the investigators assessed the expression of both human and bacterial genes in those samples.

Certain types of inflammatory immune cells carried gene expression signatures that were associated with the autoimmune flares of arthritis patients who also had periodontal disease, as well as the presence of certain oral bacteria in the blood.

Many of these oral bacteria were chemically altered by deimination; they were citrullinated. Citrullination can change the structure and function of proteins. Although citrullination can be a part of the normal function of tissues, high levels of citrullination have been linked to inflammation.

Citrullination can also create targets for ACPAs; when the normal, unconverted forms of the oral bacteria were incubated with ACPAs, the antibodies did not react, but when the citrullinated oral bacteria were exposed to ACPAs, there was a reaction. ACPAs appear to be bound to oral microbes in RA patients.

The findings have been reported in Science Translational Medicine.

The study noted that the immune response to oral microbes could be influencing RA flares, that oral microbes can trigger a specific antibody reaction in patients with both RA and gum disease, and that RA flares cause varying immune signatures, which could reflect different flare triggers.

It could be that gum disease repeatedly causes the immune system to respond, and as the immune system keeps reacting and repeatedly increasing inflammation, RA may eventually begin to emerge. More work will be needed, however, to fully understand whether gum disease is playing a causative role in the development of RA.

Source: Science Translational Medicine

Carmen Leitch

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

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.

Image credit: Pixabay

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

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

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

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

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

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

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

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

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

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

Sources: The Mount Sinai Hospital, Cell

Carmen Leitch

Long COVID still affects many people who had a case of COVID-19; even people who had mild cases …

Long COVID still affects many people who had a case of COVID-19; even people who had mild cases and were not hospitalized are at risk for the chronic disorder. Scientists and clinicians are still learning about the illness, which causes a wide range of symptoms and happens for unknown reasons. There are several hypotheses, however, and the disorder may also arise in different people for different reasons. New research has suggested that long COVID happens because particles of SARS-CoV-2, the virus that causes COVID-19, hide away in parts of the body, and the immune system becomes overactivated trying to eliminate them. The study has been reported in PLOS Pathogens.

Colorized scanning electron micrograph of a cell (brown) infected with the Omicron strain of SARS-CoV-2 virus particles (purple), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Symptoms of long COVID can include fatigue, brain fog, cough, shortness of breath, and chest pain, and these symptoms last more than four weeks after the acute phase of COVID-19. The illness is thought to impact about 20 percent of people who get COVID, noted Brent Palmer, Ph.D., an associate professor at the University of Colorado School of Medicine.

In this study, the researchers followed forty COVID-19 patients; twenty of them totally eliminated the infection and twenty developed long COVID, also known as  post-acute sequelae of COVID (PASC). The investigators used blood and stool samples from the study volunteers to identify T cells that were specific to COVID-19 and remained active after the initial infection was over.

These cells were then incubated with bits of the virus, and the scientists were able to see how frequently CD4 and CD8 T cells were reacting by generating cytokines. They found that long COVID patients carried levels of cytotoxic CD8 T cells that were as much as 100 times higher compared to people who cleared the infection.

Palmer also studies HIV infection, and he was astonished to find that about 50 percent of T cells were still directed against COVID-19 six months after their initial infection. “That’s an amazingly high frequency, much higher than we typically see in HIV, where you have ongoing viral replication all the time,” he added. “These responses were in most cases higher than what we see in HIV.”

CU pulmonologist Sarah Jolley, MD was a study co-author who obtained pulmonary data for the study volunteers. The researchers found that pulmonary function decreased as the level of COVID-19-specific T cells increased.

“That showed a really strong connection between these T cells that were potentially driving disease and an actual readout of disease, which was reduced pulmonary function. That was a critical discovery.”

The researchers have suggested that long COVID is drive by the immune system, which is increasing inflammation as it attempts to remove residual SARS-CoV-2 particles that cannot be detected with a nasal swab, but nonetheless remain. Palmer noted that some autopsies of COVID-19 patients have revealed the virus in many organs including the lungs, gut and kidney.


Additional work by Palmer and colleagues was reported in the journal Gut; this study indicated that the composition of the gut microbiomes of long COVID patients reflects an elevation of inflammatory markers. There may also be a link between the gut microbiome and the inflammation that is observed in long COVID, noted the researchers.

Palmer added that some studies have shown that antiviral medications like Paxlovid, or doses of vaccine may help relieve the symptoms of long COVID patients. This may happen because their immune systems are being given enough of a stimulatory bump to finally remove the infection, and it would show that a hidden reservoir of virus likely exists in these patients.

Sources: CU Anschutz Medical Campus, PLOS Pathogens, Gut

Carmen Leitch

Partners can accomplish amazing things, and it seems that is true for bacteria. Large colonies of bacteria called …

Partners can accomplish amazing things, and it seems that is true for bacteria. Large colonies of bacteria called biofilms become very resilient and can even gain new abilities. New research has shown that different types of bacteria can even work cooperatively to become more powerful. Scientists have revealed a collaborative relationship between Klebsiella pneumoniae and Acinetobacter baumannii, bacterial pathogens that can cause illnesses including pneumonia and urinary tract infections. They can even cause deadly infections of the bloodstream.

An SEM image of a human neutrophil (blue) interacting with two multidrug-resistant (MDR), Klebsiella pneumoniae bacteria (pink), which are known to cause severe hospital acquired, nosocomial infections. / Credit: National Institute of Allergy and Infectious Diseases (NIAID) / David Dorward; Ph.D.; NIAID

Both of these microbial pathogens have been highlighted by the World Health Organization because new antibiotics are needed to fight them. They are often identified in so-called polymicrobial infections, in which combinations of bacteria, fungi, parasites, and viruses cause illness. They are also a common problem in hospital-acquired infections.

This study has shown that Klebsiella produces metabolic byproducts that provide nutrition to Acinetobacter, and in return, Acinetobacter acts as a shield, releasing enzymes that degrade Klebsiella-destroying antibiotics. A combination of methods from various fields including microbiology, microscopy, and genetics were used in this effort; it illustrated an example of syntrophy, in which bacterial species are in a mutually symbiotic relationship, with one consuming the byproducts of another. The findings have been reported in Nature Communications.

In this research, the investigators analyzed strains of microbes isolated from a co-infection, and used an animal model to reveal “a mutually beneficial relationship” between Klebsiella and Acinetobacter. This allows Klebsiella to survive significantly higher antibiotic concentrations significantly than it would by itself, said Dr. Lucie Semenec of Macquarie University.

Co-lead study author Associate Professor Amy Cain of Macquarie University noted that the findings highlight the importance of screening for polymicrobial infections in clinical settings, because together, these pathogens are more dangerous and they feed off one another.

“This research is significant because diagnostic methods commonly look for the most dominant pathogen and therefore treatment is targeted at that,” noted Semenec. “New drugs now can be informed in future research by the molecular mechanisms we find in this work.”

Sources: Macquarie University, Nature Communications

Carmen Leitch

Even though humans are complex organisms and bacteria are single cells, and each are made of completely different …

Even though humans are complex organisms and bacteria are single cells, and each are made of completely different cell types (eukaryotic and prokaryotic cells, respectively), there are some similar immune mechanisms at work in both of them. Scientists have now learned more about how a complex found in both human and bacterial cells, a group of enzymes called ubiquitin transferases, works to regulate immune pathways. The findings, which have been reported in Nature, may provide new insights into treatments for a wide range of human diseases, suggested the researchers.

Image credit: Pixabay

“This study demonstrates that we’re not all that different from bacteria,” said senior study author Aaron Whiteley, an assistant professor at the University of Colorado Boulder. “We can learn a lot about how the human body works by studying these bacterial processes.”

Some research has suggested that the immune system found in humans has its origins in bacterial cells. Bacteria have to fight their own infections from other microbes like bacteriophages, viruses that infect bacterial cells. The CRISPR gene editing tool is derived from a bacterial immune defense.

An enzyme called cGAS (cyclic GMP-AMP synthase) can be found in humans, and a simpler version of it is also carried by bacteria; cGAS works to activate an immune defense when viral pathogens are detected.

Researchers have now analyzed the structure of bacterial cGAS, and revealed other proteins that are involved in the response to a viral infection. This study has shown that in bacteria, cGAS is modified by a simplified form of ubiquitin transferase, a crucial enzyme also found in human cells.

Bacteria are far easier to manipulate genetically compared to human cells, so this opens up a world of new research opportunities, said co-first study author Hannah Ledvina, PhD, a postdoctoral researcher. “The ubiquitin transferases in bacteria are a missing link in our understanding of the evolutionary history of these proteins.”

In this research, the scientists have also revealed two critical parts of ubiquitin transferase: Cap2 and Cap3 (CD-NTase-associated protein 2 and 3) that activate and deactivate the cGAS response, respectively.

In humans cells, ubiquitin tags also work to mark cellular garbage, like dysfunctional or unnecessary proteins that have to be degraded and disposed. Problems with this system can lead to a buildup of cellular trash, which may lead to some disorders, such as neurodegeneration.

Thus, while more research is needed, the study authors are hopeful that this work will enable us to learn more about many diseases, including autoimmune disorders like arthritis or neurodegenerative diseases such as Parkinson’s disease

Parts of the bacterial ubiquitin transferase complex, like Cap3 – the off switch, could be harnessed to eliminate some pathologies related to human disease, suggested Whiteley.

Sources: University of Colorado at Boulder, Nature

Carmen Leitch