Tag Archives: Genomics

Microbiology

How the COVID pandemic has improved genomics

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Sponsored Content by MGIMay 4 2023Reviewed by Olivia Frost
insights from industryDavide CacciharelliMolecular Biology and Genomics ProfessorUniversity of Naples

In this interview, Davide Cacchiarelli, Molecular Biology and Genomics Professor at the University of Naples talks to NewsMed about how the COVID pandemic has highlighted the vital role of genomic surveillance and improved genomics.

Please introduce yourself and what inspired your career in molecular biology and genomics?

My name is Davide Cacchiarelli, and I am a molecular biology and genomics professor at the University of Naples. I was inspired by the fact that genomics is classed as an effective tool to improve human health, dissect the molecular events happening in the cell and nucleus, and better understand how cells and organisms work.

Image Credit: ShutterStock/pinkeyes

In The Telethon Institute of Genetics and Medicine, you combine various disciplines with cell biology, molecular biology, and genomics. Why is having a multidisciplinary approach useful when making discoveries, particularly surrounding infectious diseases such as COVID?

The majority of the time, a single omic, measuring only gene expression by RNA sequencing, measuring only epigenetics, or measuring only phenotype, is insufficient to understand how a cell works.

The best solution is to combine all efforts to understand how these events happen, from the nucleus to the cell’s exterior. COVID, in particular, has been a case where acquiring one single omic or a single view of how the system works is ineffective in understanding how COVID behaviors occur in the population or clinically hospitalized patients.

We, therefore, try to combine the general information and patient outcome to get the best result regarding COVID infection.

Davide Cacciarelli at ICG17 – How the COVID pandemic has improved genomics

On what research areas are you and your team at TIGEM currently focusing?

Our group aims to answer various questions, from basic microbiology to developmental biology. Then we can re-engineer it for real regenerative medicine purposes. We also look at how we can effectively use genomics as a medical instrument that can be used to impact the healthcare of patients in our healthcare system.

You have recently co-authored a paper, “Improved SARS-CoV-2 sequencing surveillance allows the identification of new variants and signatures in infected patients.” Can you expand on that?

One of the significant issues in Italy regarding SARS-CoV-2 genome sequencing was the cost. Sequencing the COVID genome was also a tedious and elaborate procedure.

Image Credit: ShutterStock/Kateryna Kon

The main objective was first to make this approach economically affordable and create a proof of printing pulled by which this approach could become a cost-effective method for anyone and any country.

Our second approach, therefore, included integrating the genome information and the transcriptomic profiling of the patient airway epithelia. This helps us to understand how the genome evolves and allows us to track its evolution, in addition to seeing the response of the host respiratory epithelium. Finally, we implemented new ways to classify viral variants based on different characteristics using this approach.

What are the advantages of better identifying new cells, or two variants, for healthcare centers and patients?

The European Center for Disease Control has issued several requirements for next year focused on tracking respiratory viruses. One of these is tracking emerging variants as soon as possible, which we have done with COVID-19. We now know that new, specific variants can emerge in a short timeframe, so immediate tracking is crucial to help contain or at least delay the spreading of possible pathogenic variants.

MGI offers a variety of tools and technology surrounding genomics. Can you tell us more about some of the products used during your research and your experience with them?

At MGI, we have typically applied the COVID and whole genome solutions. We also have the freedom to test the stereo-seq they have in production this month. MGI can offer alternative solutions for various genome sequencing needs.

Image Credit: ShutterStock/peterschreiber.media

At present many sequencing genomic companies are coming up with different solutions. At MGI, we understand that the best genomic solution is the one that better fits your needs. With our experience, for example, with COVID, MGI had the right solution at the right moment.

How important is selecting the right sequencing technology for your research? When undertaking new research, what do you look for in a product/sequencer?

When the primary focus is not on identifying genes or mapping gene expression but on identifying or qualifying gene variants, there must be no issues in the sequencing, as the sequencing issue might be an error in the sequencing and misinterpreted data.

The error rate of MGI technology on DNB sequencing is extremely low, which offers significant benefits. Users can confidently rely on the data at the level of leaders in the field, which is what we look for when we start COVID genome sequencing.

You have often collaborated with other researchers throughout your research projects, especially concerning COVID. How vital have these collaborations been in accelerating your research?

Like many scientists who faced the COVID pandemic, I had much to learn. We used our knowledge in medical genetics and variant interpretation, and the crosstalk we had with virologists, MGI scientists, and genomic specialists was a step towards acquiring the best solution and the best effort to try to get those results as soon as possible, which is crucial for COVID sequencing.

Surprisingly, some scientists who had no interest in healthcare possessed knowledge valuable in tackling COVID issues. The circumstances and contingencies around the event forced them to think outside the box.

Do you believe that if we can understand SARS-CoV-2 better, we could better use this knowledge to prepare ourselves for future pandemics better? What advantages would this have for global health?

COVID did not give us any significant advantages for healthcare, but it may have for science. It highlighted how vital advanced genomics is to track diseases which influenced decisions at the governmental level.

Image Credit: ShutterStock/CKA

Today, several diseases require advanced genome sequencing, such as cancer diagnostics and medical genetics. Given that the issues with this problem affect a small population, you do not feel the urgency to improve specific knowledge or tests.

Therefore, the COVID pandemic has highlighted the vital role of genomic surveillance and improved genomics. Today, we have laboratories that, until two years ago, thought they could never afford to set up a genomic workflow; the pandemic forced them to enter the genomics field. Our mission as genomic scientists is to help them implement this solution in their lab because improving genomics in any lab is the best for healthcare in the future.

There is a saying, “omics for all.” As a scientist, what does that mean to you?

‘Omics for all’ has to be understood in two ways. It is critical to give everybody the chance to have access to omics. However, we need to remember that it is still a medical procedure. Thus, the omics flow offers everybody access to high-quality omics profiling of their genome, but under medical supervision.

Finally, what is the future for you in your research?

I will continue my basic research in my lab: studying how pluripotent cells and stem cells can be manipulated and organized for medical purposes. We also want to use the knowledge accumulated in the COVID pandemic to apply fast, cost-effective, and reliable genome sequencing to other types of screening.

Image Credit: ShutterStock/Anusorn Nakdee

With this in mind, we hope to screen for several hereditary cancers, for example, breast cancer inheritance. Therefore, we can effectively use the COVID strategies we set up for COVID sequencing as proof of principle to apply the sequencing to human and human disease-driving genes.

About MGI

MGI Tech Co., Ltd. (referred to as MGI) is committed to building core tools and technology to lead life science through intelligent innovation. MGI focuses on R&D, production, and sales of DNA sequencing instruments, reagents, and related products to support life science research, agriculture, precision medicine, and healthcare. MGI is a leading producer of clinical high-throughput gene sequencers, and its multi-omics platforms include genetic sequencing, mass spectrometry, medical imaging, and laboratory automation.

Founded in 2016, MGI has more than 1000 employees, nearly half of whom are R&D personnel. MGI operates in 39 countries and regions and has established multiple research and production bases around the world. Providing real-time, comprehensive, life-long solutions, its vision is to enable effective and affordable healthcare solutions for all.

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MGI Tech Co., Ltd. 

Microbiology

Can a disrupted gut microbiota contribute to anorexia nervosa pathogenesis?

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Pooja Toshniwal PahariaBy Pooja Toshniwal PahariaApr 18 2023Reviewed by Danielle Ellis, B.Sc.

In a recent study published in the journal Nature Microbiology, researchers investigated whether intestinal microbial alterations contribute to anorexia nervosa (AN) pathogenesis.

AN, a disorder associated with altered eating, has caused considerable mortality, especially among women. However, therapies based on scientific evidence are scarce. AN pathogenesis likely involves several environmental and genetic factors. Studies have reported intestinal microbial dysbiosis among AN-affected individuals. However, data were obtained from small sample sizes, and genus-level microbial alterations were analyzed by amplicon sequencing.

Study: The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice. Image Credit: Tatiana Shepeleva / ShutterstockStudy: The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice. Image Credit: Tatiana Shepeleva / Shutterstock

About the study

In the present study, researchers assessed the association between the intestinal microbiome and AN.

The team performed metabolomics and shotgun metagenomic analyses on serum and fecal samples, respectively, that were obtained from women with AN (n=77) and age- and sex-matched healthy controls (n=70). Further, the fecal microbiome was transplanted from anorexia nervosa cases to murine animals fed calories-limited diets over three weeks to simulate AN eating behavior for in vivo analysis. In addition, the team explored causal associations in silico by bidirectional mediation analysis. The intestinal microbiome was analyzed at functional, taxonomic, and genetic levels.

The team used the eating disorder inventory-3 (EDI-3) questionnaire to assess eating behaviors and insulin resistance was assessed using the homoeostatic model assessment for insulin resistance (HOMA-IR) tool. The team examined covariations between bacterial abundance at species and genus levels and clinical variables for AN cases and controls. Linear regression modeling was performed, adjusting for confounders such as age, smoking status, medications, and body mass index (BMI).

Further, the team evaluated the growth dynamics of gut bacteria by calculating peak-to-trough ratios (PTR) using the metagenomic dataset. The functional modules of gut bacteria were identified using gut-brain modules (GBMs) and gut metabolic modules (GMMs). Differences in bacterial genomics were explored based on the Canberra distance of bacterial structural variant profiles.

​​​​​​​Graphical abstract of the study workflow and findings.

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Results

Several bacterial organisms (including Clostridium) were altered among individuals with anorexia nervosa and were associated with mental well-being and eating behavior estimates. Bacterial functional-type modules related to neurotransmitter degradation were enriched among those with anorexia nervosa. Further, several structural variants (SVs) in bacterial organisms were associated with the metabolic characteristics of anorexia nervosa.

The findings indicated a probable role of the intestinal microbiome in AN-associated changes concerning satiety and the metabolism of secondary bile acids. The metabolomic analysis indicated an elevation in metabolites linked to lowered food consumption (including taurine-hyodeoxycholic acid, taurine-α-muricholic acid, and indole-3-propionic acid molecules). Causal inference analysis indicated that serological bacterial metabolites probably mediate the effect of gut microbial alterations on anorexia nervosa. At the phylum level, AN microbiome samples showed lowered Actinobacteriota and Bacteroidota counts. Among families of bacteria, Christensenellaceae species, particularly CAG-138, showed the most significant enrichment in AN.

At the genus level, elevated Lactobacillus counts were observed in the AN microbiota. The Ruminococcacea-enterotype was more prevalent in cases of AN. Species-level analysis indicated greater β-diversity among AN-affected women. In AN, Roseburia inulinivorans and Roseburia intestinalis were depleted, whereas those of Erysipelatoclostridium ramosum, Blautia species CAG, and Enterocloster bolteae innocuum (Clostridium) were increased. Clostridium counts correlated positively with eating disorder scores. The abundance of Bifidobacterium and Parasutterella, in absolute terms, showed positive correlations with perfectionism and body dissatisfaction, respectively.

Absolute Brachyspira count showed a positive association with ‘drive for thinness’ markers in anorexia nervosa. Median values for PTR markedly differed between individuals with AN and controls. Women with AN were leaner, had lower fasting serological insulin, glucose, and C-reactive protein (CRP) levels, and were more sensitive to insulin than controls. Bacterial organisms with significant growth retardation, among AN case individuals included Alistipes finegoldii, Akkermansia muciniphila, Eubacterium siraeum, Coprococcus catus, SS3/4, and Odoribacter splanchnicus.

In addition, the intestinal virome was altered among AN-affected individuals, including lowered bacterial-viral interactions, due to attenuated interactions of viruses with short-chain fatty acid (SCFA)-producing bacteria, including Roseburia inulinivorans, Roseburia hominis, and Faecalibacterium prausnitzii. The team observed greater viral richness and Shannon diversity in the fecal samples of AN cases compared to controls. Notably, 25/30 viruses increased in AN were Lactococcus bacteriophages. The abundance of GBMs for serotonin synthesis and degradation of tryptophan, glutamate, and dopamine, were enriched in AN.

The team detected 2,423 and 5,056 variable SVs and deletion SVs, respectively, across 56 species of bacteria, including Bacteroides uniformis, Faecalibacterium prausnitzii, Parabacteroides distasonis, Methanobrevibacter smithii. Individuals with AN lacking the genomic region of B. uniformis had greater scores for self-denial and bulimia. The genetic deletion in B. uniformis could result in the deficiency of thiamine, a vitamin associated with intestinal and mental health. The serotonin synthesis module causally affected BMI through glycoursodeoxycholic acid, which is upregulated by serotonin.

Serum leucine mediated the influence of B. vulgatus counts on glucose homeostasis. Mice receiving AN individuals’ fecal transplants initially lost more weight with a slower gain of weight with time than those receiving fecal transplants of control individuals. The finding was related to greater levels of hypothalamic appetite-suppressing genes and thermogenesis-associated genes in the adipose tissues of mice receiving fecal transplants from individuals with AN.

Based on the study findings, gut microbial disruptions may contribute to the pathogenesis of AN.

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Journal reference:
Microbiology

Genomic study reveals Babesia duncani’s pathogenicity and virulence

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Reviewed by Emily Henderson, B.Sc.Apr 13 2023

‘Tis the season for hiking now that spring has arrived and temperatures are on the upswing. But with hikes come insect bites and on the increase in North America is babesiosis, a malaria-like disease spread especially between May and October by a tick.

Indeed, recent research suggests an increase in the incidence of diseases transmitted by ticks around the world, not just the United States and Canada, due likely to climate change and other environmental factors. Among the tick-borne pathogens, Babesia parasites, which infect and destroy red blood cells, are considered a serious threat to humans and animals. All cases of human babesiosis reported in the United States have been linked to either Babesia microti, B. duncani, or a B. divergens-like species.

Now a research team led by scientists at the University of California, Riverside, and Yale University reports the first high-quality nuclear genome sequence and assembly of the pathogen B. duncani. The team also determined the 3D genome structure of this pathogen that resembles Plasmodium falciparum, the malaria-causing parasite.

“Our data analysis revealed that the parasite has evolved new classes of multigene families, allowing the parasite to avoid the host immune response,” said Karine Le Roch, a professor of molecular, cell and systems biology at UC Riverside, who co-led the study with Choukri Ben Mamoun, a professor of medicine at Yale University.

According to Le Roch, who directs the UCR Center for Infectious Disease Vector Research, the study, published today in Nature Microbiology, not only identifies the molecular mechanism most likely leading to the parasite’s pathogenicity and virulence, but also provides leads for the development of more effective therapies.

By mining the genome and developing in vitro drug efficacy studies, we identified excellent inhibitors of the development of this parasite -; a pipeline of small molecules, such as pyrimethamine, that could be developed as effective therapies for treating and better managing human babesiosis. Far more scientific and medical attention has been paid to B. microti. The genome structure of B. duncani, a neglected species until now, will provide scientists with important insights into the biology, evolution, and drug susceptibility of the pathogen.”

Karine Le Roch, professor of molecular, cell and systems biology at UC Riverside

Human babesiosis caused by Babesia duncani is an emerging infectious disease in the U.S. and is often undetected because healthy individuals do not usually show symptoms. It has, however, been associated with high parasite burden, severe pathology, and death in multiple cases. Despite the highly virulent properties of B. duncani, little was known about its biology, evolution, and mechanism of virulence, and recommended treatments for human babesiosis against B. duncani are largely ineffective.

A strong immune system is required to fight the pathogen. A compromised immune system could lead to flu-like illness. The tick that spreads babesiosis is mostly found in wooded or grassy areas and is the same tick that transmits bacteria responsible for Lyme disease. As a result, around 20% of patients with babesiosis are co-infected with Lyme disease.

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B. duncani mostly infects deer, which serve as the reservoir host during the pathogen’s asexual development. The parasite’s sexual cycle occurs in the tick after the tick bites the infected deer. When this tick bites humans, infection begins. The full life cycle of Babesia parasites has not yet been determined. The tick that spreads babesiosis, called Dermacentor albipictus, lives longer than mosquitoes and could facilitate a long life cycle for B. duncani.

Even though scientists are discovering more Babesia species, diagnostics are mostly developed for B. microti. Le Roch is already working with Stefano Lonardi, a professor of computer science and engineering at UCR and co-first author of the study, on new Babesia strains that have evolved.

“The Babesia genomes are not very long,” said Lonardi, who assembled the B. duncani strain. “But they are challenging to assemble due to their highly repetitive content and can require years of research. Once the genome is assembled and annotated, it can provide valuable information, such as how the genes are organized, which genes are transcribed during infection, and how the pathogen avoids the host’s immune system.”

In older and immunocompromised people, if B. duncani is left unattended, babesiosis could worsen and lead to death. Once the pathogen enters the body and red blood cells start to get destroyed, fever, headache, and nausea can follow. People who get bitten by the ticks often don’t feel the bite, which complicates diagnosis. Skin manifestations of babesiosis are rare, Lonardi said, and difficult to separate from Lyme disease.

Le Roch and Lonardi urge people to be mindful of ticks when they go hiking.

“Check yourself for tick bites,” Le Roch said. “When you see your physician don’t forget to let them know you go hiking. Most physicians are aware of Lyme disease but not of babesiosis.”

Next the team plans to study how B. duncani survives in the tick and find novel vector control strategies to kill the parasite in the tick.

Le Roch, Mamoun, and Lonardi were joined in the study by colleagues at UCR, Yale School of Medicine, Université de Montpellier (France), Instituto de Salud Carlos III (Spain), Universidad Nacional Autónoma de México, and University of Pennsylvania. Pallavi Singh at Yale and Lonardi contributed equally to the study. The B. duncani genome, epigenome, and transcriptome were sequenced at UCR and Yale.

The study was supported by grants from the National Institutes of Health, Steven and Alexandra Cohen Foundation, Global Lyme Alliance, National Science Foundation, UCR, and Health Institute Carlos III.

Source:

University of California – Riverside

Journal reference:

Singh, P., et al. (2023). Babesia duncani multi-omics identifies virulence factors and drug targets. Nature Microbiology. doi.org/10.1038/s41564-023-01360-8.

Microbiology

Tulane receives up to $16 million to move nasal pneumonia vaccine from the lab to clinical trials

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Reviewed by Emily Henderson, B.Sc.Mar 24 2023

The National Institute of Allergy and Infectious Diseases awarded an up to $16 million contract to Tulane University to bring to phase one clinical trial a nasal spray vaccine university researchers invented to thwart antibiotic-resistant Klebsiella pneumoniae, a leading cause of pneumonia.

Antibiotic-resistant bacteria are on the rise and are a significant cause of infections requiring hospitalization among children and the elderly. As doctors try to find new types of antibiotics to fight these so-called superbugs, Tulane University School of Medicine researchers Elizabeth Norton, PhD, and Jay Kolls, MD, inventors of the vaccine, are working to protect people before they are exposed to the pathogens in the first place.

“Multidrug-resistant bacteria are causing more severe infections and are a growing public health threat. Vaccines targeting these pathogens represent the most cost-effective option, particularly if you can use this vaccine to prevent or treat the infection in high-risk individuals,” said Norton, principal investigator and associate professor of microbiology and immunology. “Right now, there is no vaccine on the market that targets this type of pneumonia.”

Klebsiella pneumoniae is the third leading cause of hospital-acquired pneumonia and the second leading cause of bloodstream infections with the highest incidence of serious infections. It is also a major cause of childhood pneumonia in parts of Asia. The Tulane vaccine would target high-risk populations such as immunocompromised individuals, diabetics or organ transplant recipients.

Norton said that while the vaccine targets the Klebsiella bacteria, its unique design gives it the potential to be cross-reactive to other members of the Enterobacteriaceae family, the antibiotic-resistant bacterial species behind many hospital-acquired infections, including E. coli.

The vaccine, called CladeVax, is designed to efficiently target mucosa in the nose, throat and lungs to protect the area most at risk for infection.

The nasal spray vaccine uses an adjuvant -; a compound that stimulates the immune system -; named LTA1 that Norton developed at Tulane. That adjuvant, which is made using a protein derived from the E. coli bacteria, will be combined with a series of proprietary antigens identified by the Kolls lab that include outer membrane proteins from the target bacteria.

This is an entirely novel vaccine platform, from the use of the adjuvant to the needle-less route of administration. This represents an entirely new class of vaccines for bacteria that elicits protection in two ways -; both antibody and T-cell immunity. All current pneumonia vaccines only elicit antibodies against surface carbohydrates. Our platform has the potential advantage of providing a much broader protection against pneumonia.”

Jay Kolls, co-principal investigator, and the John W. Deming Endowed Chair in Internal Medicine

Tulane researchers will first test vaccine formulations in animal models and nonhuman primates for dosing and safety before advancing to clinical trials. The project will include collaborators at Tulane National Primate Research Center, the School of Public Health and Tropical Medicine, Tulane Clinical Translational Unit, and the University of North Carolina as well as contractors for GMP manufacturing.

“If this succeeds, we will have another arsenal for the growing number of antibiotic resistant sources of pneumonia or bloodstream infections,” Norton said. “And we can hopefully expand this nasal spray delivery platform to other infections, working on a single, combination vaccine that is needle-less and targets several organisms at once.”

Source:

Tulane University

Microbiology

Researchers Decipher the Inner Workings of a Bacterium

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A group led by Professor Ralf Rabus, a microbiologist at the University of Oldenburg, and his Ph.D. student Patrick Becker has made significant advancements in comprehending the cellular processes of a widespread environmental bacterium. The team conducted an extensive analysis of the entire metabolic network of the bacterial strain Aromatoleum aromaticum EbN1T and utilized the findings to construct a metabolic model that allows them to forecast the growth of these microbes in various environmental conditions.

According to their report in the journal mSystems, the researchers uncovered surprising mechanisms that enable the bacteria to adjust to fluctuating environmental conditions. These results are crucial for the study of ecosystems, where the Aromatoleum strain, as a representative of a significant group of environmental bacteria, can act as a model organism. The findings could also have implications for the cleanup of contaminated sites and biotechnological applications.

The studied bacterial strain specializes in the utilization of organic substances that are difficult to break down and is generally found in soil and in aquatic sediments. The microbes thrive in a variety of conditions including oxygen, low-oxygen, and oxygen-free layers, and are also extremely versatile in terms of nutrient intake. They metabolize more than 40 different organic compounds including highly stable, naturally occurring substances such as components of lignin, the main structural material found in wood, and long-lived pollutants and components of petroleum.

In particular, substances with a benzene ring composed of six carbon atoms, known as aromatic compounds, can be biodegraded by these microbes – with or without the aid of oxygen. Due to these abilities, Aromatoleum plays an important environmental role in the complete degradation of organic compounds in soil and sediments to carbon dioxide – a process which is also useful in biological soil remediation.

The aim of the current study was to gain a holistic understanding of the functioning of this unicellular organism. To this end, the researchers cultivated the microbes under both oxic and anoxic conditions – i.e. with and without oxygen – using five different nutrient substrates. For each of these ten different growth conditions, they grew 25 cultures and then examined the various samples using molecular biology methods (technical term: multi-omics) which enable simultaneous analysis of all the transcribed genes in a cell, all the proteins produced, and all its metabolic products.

“With this systems biology approach, you gain a deep understanding of all the inner workings of an organism,” explains Rabus, who heads the General and Molecular Microbiology research group at the University of Oldenburg’s Institute for Chemistry and Biology of the Marine Environment (ICBM). “You break down the bacterium into its individual components and then you can put them back together – in a model that predicts how fast a culture will grow and how much biomass it will produce.”

Through their meticulous work, the researchers obtained a comprehensive understanding of the metabolic reactions of this bacterial strain. They found that around 200 genes are involved in the degradation processes and determined which enzymes break down the substances added as nutrients and via which intermediates the various nutrients are decomposed. The scientists incorporated their findings about the metabolic network into a growth model, and demonstrated that the model predictions largely corresponded to the measured data.

“We can now describe the organism with a level of precision that has so far only been possible with very few other bacteria,” says Rabus. This holistic view of the bacteria’s cellular inner workings forms the basis for a better understanding of the interactions between the analyzed strain (and related bacteria) and their biotic and abiotic environment, he adds, and can also help scientists to better predict the activity of these unicellular organisms in polluted soils and thus, for example, determine the optimal conditions for the remediation of a contaminated site.

By combining different methods, the team was able to uncover unexpected mechanisms in the metabolism of these bacteria. Much to the researchers’ surprise, it emerged that the microbe produces several enzymes which they cannot use under the given growth conditions – which at first glance would seem to be a superfluous expenditure of energy. “Usually the bacterial cells detect whether oxygen is present in their environment and then, via specific mechanisms, activate only the nutrient-specific metabolic pathway with the corresponding enzymes,” Rabus explains.

But with some substrates, the microbe produced all the enzymes for aerobic and anaerobic degradation pathways regardless of oxygen levels – even though some of these enzymes were entirely superfluous. Rabus suspects that this apparent waste is in fact a strategy for surviving in an unstable environment: “Even if oxygen levels suddenly fluctuate – which is often the case in natural environments – Aromatoleum remains flexible and can utilize this nutrient and produce energy as required,” the microbiologist explains, adding that so far, no other bacteria are known to use such a mechanism.

Reference: “Systems Biology of Aromatic Compound Catabolism in Facultative Anaerobic Aromatoleum aromaticum EbN1T” by Patrick Becker, Sarah Kirstein, Daniel Wünsch, Julia Koblitz, Ramona Buschen, Lars Wöhlbrand, Boyke Bunk and Ralf Rabus, 29 November 2022, mSystems.
DOI: 10.1128/msystems.00685-22

University of Oldenburg

Microbiology

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

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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

Microbiology

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

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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

Microbiology

Study finds unique epigenetic biosignature in individuals with post-COVID syndrome

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Reviewed by Emily Henderson, B.Sc.Feb 28 2023

A reprogramming of which genes are active, and which are not, is visible in post-COVID sufferers. This is shown in a study from Linköping University, Sweden, on a small group of individuals. The researchers can see that genes associated with taste and smell, as well as cell metabolism, are affected in individuals with post-COVID syndrome. These findings may ultimately contribute to the development of new diagnostic tools for this and similar diseases.

There are many external factors that can affect which of all the genes in a cell are used at a certain point in time. The body’s ability to switch genes on and off contributes to our ability to adapt to various conditions. This gene use regulation is called epigenetics.

One of the regulation mechanisms entails that a small chemical group, a methyl group, is switched on and removed from the DNA strand. Reduced methylation of a gene may be a sign of it becoming easier for the cell to read and use, whereas high methylation most often means that the gene is not used. The researchers in Maria Lerm’s research group at Linköping University have previously found that exposure to the tuberculosis bacteria is visible in individuals’ DNA by looking at certain epigenetic changes.

In their new study, published in Clinical Epigenetics, the researchers studied blood samples from ten individuals having had persistent post-COVID symptoms for more than 12 weeks. The most common symptoms were a feeling of not being able to draw in enough air, palpitations, muscle weakness and loss of smell and taste.

These individuals were compared with two other groups: healthy COVID-19 convalescents, and individuals who had not had COVID-19 when the samples were taken. The researchers measured the methylation pattern on 850,000 sites of the DNA and then used an algorithm that can find data similarities and differences. It turned out that the three groups differed from each other and had distinct methylation profiles. The researchers then identified the genes that differ in methylation patterns between the groups.

“We have found that, for example, signaling pathways that control taste and smell have been affected. This confirms that the epigenetic differences may in fact be associated with the set of symptoms and be physiologically relevant,” says Maria Lerm, Professor of Medical Microbiology at the Department of Biomedical and Clinical Sciences, BKV, at Linköping University.

A previous study conducted by the research group concerned individuals who had recently recovered from COVID-19 and who showed a similar epigenetic reprogramming of signaling pathways associated with taste and smell.

In their new study, the researchers also found epigenetic changes in what is known as the angiotensin-2 system in post-COVID sufferers. This could be biologically relevant as the coronavirus which causes COVID-19, i.e., the SARS-CoV-2 virus, uses the angiotensin-2 system to enter and infect cells.

One of several conditions similar to post-covid is chronic fatigue syndrome, CFS, which is also known as myalgic encephalomyelitis, ME.

“One important finding is that we can see that the cells’ energy factories, the mitochondria, are affected in the post-COVID group. Other studies have shown that the cells’ energy factories have also been affected in cases of chronic fatigue,” says Maria Lerm.

There is currently no test that doctors can use to decide whether a person has post-COVID syndrome. The researchers are hoping that their recent findings can contribute to the development of diagnostic tools for health care providers, tools that might perhaps even make it possible to distinguish post-COVID from similar conditions.

The study was financed with support from the Swedish Heart Lung Foundation and the Swedish Research Council. The methylation pattern of study participants’ DNA was analyzed at Clinical Genomics, a SciLifeLab platform at Linköping University and Region östergötland.

Source:

Linköping University

Journal reference:

Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells, Frida Nikesjö, Shumaila Sayyab, Lovisa Karlsson, Eirini Apostolou, Anders Rosén, Kristofer Hedman and Maria Lerm, (2022), Clinical Epigenetics 14:172, published online on 14 December 2022 https://doi.org/10.1186/s13148-022-01398-1

Microbiology

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

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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

Microbiology

Researchers were able to take advantage of “an incredibly unique opportunity” to study the microbial life that rapidly …

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Researchers were able to take advantage of “an incredibly unique opportunity” to study the microbial life that rapidly colonized a short-lived island that formed in the South Pacific after a volcanic eruption. This work, reported in mBio, revealed a variety of unique microbes that could metabolize sulfur and gases in their local atmosphere, like the extremophile microbes that are sometimes found near hydrothermal vents or in hot springs. The lead author of a report on the findings, CIRES graduate student Nick Dragone noted that, “These types of volcanic eruptions happen all over the world, but they don’t usually produce islands.”

Hunga Tonga-Hunga Ha'apai in 2017 / Image credit: NASA/Damien Grouille/Cecile Sabau

But in 2015, an eruption of a submarine volcano created the Hunga Tonga Hunga Ha’apai Island, which existed for seven years. The formation of the island is described in the NASA video below. During the island’s lifetime, the study authors collected soil samples from the site and sent them off to the laboratory so that DNA in those samples could be extracted. By analyzing the genetic sequences, the scientists determined that some unusual bacteria were living on the island.

The investigators said they were surprised by the findings. Instead of revealing organisms that accompany the retreat of glaciers, or marine microbes like cyanobacteria, they found something else — an unusual bunch of microbes that metabolize sulfur and atmospheric gases.

On January 15, 2022, the research team got another surprise; there was another eruption near the island, which destroyed the entire landmass in the 21st century’s largest volcanic explosion (so far). Now, the site can’t be monitored ever again.

“We were all expecting the island to stay,” said Dragone. “In fact, the week before the island exploded we were starting to plan a return trip.”

Luckily the team was able to make use of the island while it existed. “No one had ever comprehensively studied the microorganisms on this type of island system at such an early stage before,” added Dragone.

The short life of the island, and its volcanic origins, fostered an unusual community of microbes, as well as an international group of researchers working together. Learning more about this unique type of microbial community can provide insights into how ecosystems might start to develop, even before organisms like plants or animals arrive on the scene, noted corresponding study author and CIRES fellow Noah Fierer, a professor of ecology and evolutionary biology at CU Boulder.

Sources: University of Colorado Boulder (CU Boulder) and Cooperative Institute for Research in Environmental Sciences (CIRES), mBio


Carmen Leitch