That, at its simplest, is the approach Mohamed Seleem’s lab at the Center for One Health Research has found may be a key treatment strategy in the battle against Candida auris, a frighteningly deadly fungal pathogen discovered in 2009 that is considered an urgent threat by the Centers for Disease Control and Prevention (CDC).
Candida auris, first discovered in Japan as an ear infection, has a staggering 60 percent mortality rate among those it infects, primarily people with compromised health in hospitals and nursing homes.
Recently, Seleem and Ph.D. students Yehia Elgammal and Ehab A. Salama published a paper in the American Society for Microbiology’s Antimicrobial Agents and Chemotherapy journal detailing the potential use of atazanavir, an HIV protease inhibitor drug, as a new avenue to improving the effectiveness of existing antifungals for those with a Candida auris infection.
A perfect storm of antimicrobial resistance, global warming and the COVID-19 pandemic has resulted in the rapid spread of Candida auris around the world, said Seleem, director of the center, a collaboration between the Virginia-Maryland College of Veterinary Medicine and the Edward Via College of Osteopathic Medicine.
We don’t have lots of drugs to use to treat fungal pathogens. We have only three classes of antifungal drugs. With a fungal pathogen, it’s often resistant to one class, but then we have two other options. What’s scary about Candida auris is it shows resistance to all three classes of the antifungal.
The CDC has a list of urgent threats, but on that list there is just one fungal pathogen, which is Candida auris. Because it’s urgent, we need to deal with it.”
Mohamed Seleem, the Tyler J. and Frances F. Young Chair in Bacteriology at Virginia Tech
Widespread use of fungicides in agriculture, in addition to the three classes of antifungal drugs used widely in medicine, has contributed to fungal pathogens developing more resistance, particularly Candida auris.
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Also, its rise has been linked to rising global temperatures and to easier spread through hospitals filled with COVID-19 patients in recent years during the global pandemic.
Atazanavir, an HIV protease inhibitor drug, has been found by Seleem’s lab to block the ability of Candida auris to excrete antifungals through its efflux pumps.
Think of a boat taking on water and hoses siphoning that water out of the boat to keep it afloat. Atazanavir stops up the hoses.
That allows the azole class of antifungal drugs to not be expelled as easily and perform better against Candida auris, the Seleem lab’s research has found.
The research on atazanavir builds on work three years ago by Seleem’s lab, then at Purdue University, finding potentially similar benefit in lopinavir, another HIV protease inhibitor.
HIV protease drugs are already in wide use among HIV patients, who can also be extra susceptible to Candida auris. Some HIV patients have likely been taking HIV protease drugs and azole-class antifungals in tandem for separate purposes, providing a potential source of already existing data that can be reviewed on whether those patients had Candida auris and what effects the emerging pathogen had on them.
Repurposing drugs already on the market for new uses can allow those treatments to reach widespread clinical use much more rapidly than would happen with the discovery of an entirely new drug, as existing drugs have already been tested and approved by the Food and Drug Administration and have years of further observation of effects in prescriptive use.
In 2022, the Center for One Health Research received a $1.9 million grant from the National Institutes of Health for the Seleem lab’s research on repurposing already approved drugs for treating gonorrhea.
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While effective vaccines for COVID-19 should have heralded the benefits of mRNA vaccines, fear and misinformation about their supposed dangers circulated at the same time. These misconceptions about mRNA vaccines have recently spilled over into worries about whether their use in agricultural animals could expose people to components of the vaccine within animal products such as meat or milk.
In fact, a number of states are drafting or considering legislation outlawing the use of mRNA vaccines in food animals or, at minimum, requiring their labeling on animal products in grocery stores. Idaho introduced a bill that would make it a misdemeanor to administer any type of mRNA vaccine to any person or mammal, including COVID-19 vaccines. A Missouri bill would have required the labeling of animal products derived from animals administered mRNA vaccines but failed to get out of committee. Arizona and Tennessee have also proposed labeling bills. Several otherstate legislatures are discussing similar measures.
I am a researcher who has been making vaccines for a number of years, and I started studying mRNA vaccines before the pandemic started. My research on using mRNA vaccines for cattle respiratory viruses has been referenced by social media users and anti-vaccine activists who say that using these vaccines in animals will endanger the health of people who eat them.
But these vaccines have been shown to reduce disease on farms, and it’s all but impossible for them to end up in your food.
In food animals, several types of vaccines have long been available for farmers to protect their animals from common diseases. These include inactivated vaccines that contain a killed version of a pathogen, live attenuated vaccines that contain a weakened version of a pathogen and subunit vaccines that contain one part of a pathogen. All can elicit good levels of protection from disease symptoms and infection. Producing these vaccines is often inexpensive.
Inactivated and subunit vaccines often do not produce a strong enough immune response, and pathogens can quickly mutate into variants that limit vaccine effectiveness. The weakened pathogens in live attenuated vaccines have the remote possibility of reverting back to their full pathogenic form or mixing with other circulating pathogens and becoming new vaccine-resistant ones. They also must be grown in specific cell cultures to produce them, which can be time-consuming.
There are also several pathogens – such as porcine reproductive and respiratory syndrome virus, foot and mouth disease virus, H5N1 influenza and African swine fever virus – for which all three traditional approaches have yet to yield an effective vaccine.
Another major drawback for all three of these vaccine types is the time it takes to test and obtain federal approval to use them. Typically, animal vaccines take three or more years from development to licensure by the U.S. Department of Agriculture. Should new viruses make it to farms, playing catch-up using traditional vaccines could take too long to contain an outbreak.
All cells use mRNA, which contains the instructions to make the proteins needed to carry out specific functions. The mRNA used in vaccines encode instructions to make a protein from a pathogen of interest that immune cells learn to recognize and attack. This process builds immunological memory, so that when a pathogen carrying that same protein enters the body, the immune system will be ready to mount a quick and strong response against it.
Compared to traditional vaccines, mRNA vaccines have several advantages that make them ideal for protecting people and farm animals from both emerging and persistent diseases.
Unlike killed or subunit vaccines, mRNA vaccines increase the buildup of vaccine proteins in cells over time and train the immune system using conditions that look more like a viral infection. Like live attenuated vaccines, this process fosters the development of strong immune responses that may build better protection. In contrast to live attenuated viruses, mRNA vaccines cannot revert to a pathogenic form or mix with circulating pathogens. Furthermore, once the genetic sequence of a pathogen of interest is known, mRNA vaccines can be produced rather quickly.
The mRNA in vaccines can come in either a form that is structurally similar to what is normally found in the body, like those used in COVID-19 vaccines for people, or in a form that is self-amplifying, called saRNA. Because saRNA allows for higher levels of protein synthesis, researchers think that less mRNA would be needed to generate similar levels of immunity. However, a COVID-19 saRNA vaccine for people developed by biopharmaceutical company CureVac elicited less protection than traditional mRNA approaches.
Merck’s Sequivity is currently the only saRNA vaccine licensed for use in animals, and it is available by prescription to protect against swine flu in pigs.
All mRNA vaccines are made in the laboratory using methods that were developed decades ago. Only recently has the technology advanced to the point where the body doesn’t immediately reject it by activating the antiviral defenses intrinsic to each of your cells. This rejection would occur before the immune system even had the chance to mount a response.
The COVID-19 mRNA vaccines used in people mix in modified nucleotides – the building blocks of RNA – with unmodified nucleotides so the mRNA can hide from the intrinsic antiviral sensors of the cell. These modified nucleotides are what allow the mRNA to persist in the body’s cells for a few days rather than just a few hours like natural mRNAs.
New methods of delivering the vaccine using lipid nanoparticles also ensure the mRNA isn’t degraded before it has a chance to enter cells and start making proteins.
Despite this stability, mRNA vaccines do not last long enough within animals after injection for any component of the vaccine to end up on grocery store shelves. Unlike for human vaccines, animal vaccine manufacturers must determine the withdrawal period in order to obtain USDA approval. This means any component of a vaccine cannot be found in the animal prior to milking or slaughter. Given the short lifespan of some of the agriculture animals and intensive milking schedules, withdrawal periods often need to be very short.
Between the mandatory vaccine withdrawal period, flash pasteurization for milk, degradation on the shelf and the cooking process for food products, there could not be any residual vaccine left for humans to consume. Even if you were to consume residual mRNA molecules, your gastrointestinal tract will rapidly degrade them.
Several mRNA vaccines for use in animals are inearly stagesof development. Merck’s USDA-licensed Sequivity does not use the modified nucleotides or lipid nanoparticles that allow those vaccine components to circulate for slightly longer periods in the body, so long-term persistence is unlikely.
Like in people, animal vaccines are tested for their safety and effectiveness in clinical trials. Approval for use from the USDA Center for Vaccine Biologics requires a modest level of protection against infection or disease symptoms. As with all animal vaccines, future mRNA vaccines will also need to be fully cleared from the animal’s body before they can be used in animals for human consumption.
Whether mRNA vaccines will displace other vaccine types for livestock is yet to be determined. The cost of manufacturing these vaccines, their need to kept very cold and warm up before use to avoid degradation, and the efficacy of different types of mRNA vaccines all still need to be addressed before large-scale use can take place.
Traditional vaccines for food animals have protected them against many diseases. Limiting the use of mRNA vaccines right now would mean losing a new way to protect animals from pesky pathogens that current vaccines can’t fend off.
SHENZHEN, China, 10 May 2023 – MGI Tech Co. Ltd. (MGI), a company committed to building core tools and technology to lead life science, today shared that a total of nearly 60,000 samples have been sequenced among 21 institutes and over 10 participating nations throughout Europe, as part of the Million Microbiome of Humans Project (MMHP) that was officially launched in 2019.
Image Credit: MGI
The project was launched as a joint effort by the Karolinska Institute of Sweden, Shanghai National Clinical Research Center for Metabolic Diseases in China, the University of Copenhagen in Denmark, Technical University of Denmark, MetaGenoPolis at the National Research Institute for Agriculture, Food and Environment (INRAE) in France, and the Latvian Biomedical Research and Study Center. Relying on MGI’s core DNBSEQ™ technology, MMHP aims to sequence and analyze microbial DNA from a million human samples to construct a microbiome map of the human body and build the world’s largest human microbiome database.
The rise of microbial metagenomic sequencing
Since the first description of human microbiome was published in 2010, the field of human microbiome has moved fast from sampling hundreds of individuals to thousands. Advances in genome sequencing has enabled researchers to better characterize the composition of the microbiome through identification of unculturable microbes. It has also allowed them the opportunity to study how the microbiome influences the development of some cancers and drug responses.
Metagenomics, coupled with high-throughput sequencing technologies, have revolutionized microbial ecology. Today, metagenomic sequencing has become both a powerful and popular tool for identifying and classifying complex microbial communities. It facilitates accelerated discovery of new markers that translate to virulence or antibiotic resistance, as well as de novo discovery and characterization of novel species and assembly of new genomes. Besides human microbiome, it is highly applicable in agricultural microbiome studies, environmental microbiome studies, pathogen surveillance and identification, and monitoring of antimicrobial resistance genes.
Indeed, the global metagenomic sequencing market was estimated to be worth USD 1.86 billion in revenue in 2022 and is poised to reach USD 4.33 billion by 2027, growing at a CAGR of 18.4% during the forecast period. In particular, Europe and Africa account for approximately 29.7% market share from the globe, ranking second after North America at 45.6%. Thanks to continuous technological innovations in high-throughput sequencing platforms, the metagenomic sequencing market within Europe and Africa is projected to grow from USD 551.7 million in 2022 to 1.29 billion by 2027, presenting huge market opportunities and providing local institutions with the impetus to invest and get involved.
Image Credit: MGI
An optimized workflow with MGI’s cutting-edge technology
Equipped with MGI’s innovative lab systems, the MMHP Consortium guarantees high-throughput processes, extreme precision, and high quality data output. The dedicated, one-stop workflow begins with sample transfer on MGISTP-7000* high-throughput automated sample transfer processing system. It then goes through nucleic acid extraction and library preparation on MGISP-960 high-throughput automated sample preparation system, a flexible and fully automated workstation capable of processing 96 samples per run. MGISP-960’s fully automatic operation design allows DNA extraction of 50,000 samples per year and library preparation of 25,000 samples per year. MGISP-Smart 8, the professional automated pipetting robot, equipped with an independent 8 pipetting channel can be used for the pooling, normalization and DNB making. Lastly, DNBSEQ-T7* ultra-high throughput sequencer and DNBSEQ-G400* versatile benchtop sequencer enables an efficient, productive, and streamlined sequencing experience.
“We are very focused on data quality, cost and time. After contrasting DNBSEQ™ technology by MGI with other sequencing technologies, we are convinced that MGI’s products have met high industry standards and provide a very good user experience,” commented Professor Lars Engstrand, Research Director of Center for Microbial Translational Research (CMTR) at Karolinska Institutet. “MGI’s platforms have enabled our team to upgrade our original microbiological research from 16SrRNA gene amplicon sequencing to shotgun metagenomic sequencing. I look forward to introducing more equipment and super-large projects as human microbiome emerges as a crucial diagnostic and treatment method in precision medicine.”
The next chapter in microbiomics
“Microbiomics will be part of precision medicine in the future, and data from the microbiome biobank that will result from MMHP will be leveraged for therapeutic R&D,” said Professor Stanislav Dusko Ehrlich of University College London, UK. “With 21 public and private institutions and 10+ countries currently involved in MMHP, we are actively looking for more research groups to take part in this landmark international microbiological research partnership and help generate the world’s biggest free-access human microbiome database.”
Since the inception of MMHP, MGI has played an important role in providing the program with state-of-the-art research platforms and technologies. Now entering its second phase towards sequencing and analyzing a final total of one million samples, the project welcomes further exchange and participation from relevant organizations to jointly promote research and applications of cutting-edge translational medicine in the field of microbiome. Those interested can fill the application form on www.mgi-tech.eu/mmhp.
About MGI
MGI Tech Co. Ltd. (MGI), headquartered in Shenzhen, is committed to building core tools and technology to lead life science through intelligent innovation. Based on its proprietary technology, MGI focuses on research & development, production and sales of 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*, medical imaging, and laboratory automation. MGI’s mission is to develop and promote advanced life science tools for future healthcare. For more information, please visit the MGI website or connect with us on Twitter, LinkedIn or YouTube.
*Unless otherwise informed, StandardMPS and CoolMPS sequencing reagents, and sequencers for use with such reagents are not available in Germany, Spain, UK, Sweden, Italy, Czech Republic, Switzerland and Hong Kong (CoolMPS is available in Hong Kong).
*For Research Use Only. Not for use in diagnostic procedures (except as specifically noted).
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.
Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.
Drug-resistant infections are one of the most serious threats to global health, and there is an urgent need to develop new, effective antimicrobials. One promising solution could be antimicrobial peptides (AMPs). These are compounds naturally produced by most living organisms, including animals, and have important roles in innate immunity, our first line of defence against bacterial infections.
However, some AMPs are also used widely in livestock production, both to control infections and as growth promoters. This has raised concerns that agricultural AMP use may generate cross-resistant bacteria that could then overcome the human innate immune response.
In this new study, led by the University of Oxford, researchers have demonstrated that evolution of such cross-resistant bacteria is not only possible, but also highly likely.
To test the idea, the researchers used colistin, an AMP produced by a bacterium (Bacillus polymyxa) that is chemically and functionally similar to AMPs produced in animals. Colistin has become increasingly important as a ‘last-line of defence’ for treating infections caused by multidrug-resistant bacteria. However, extensive use of colistin in livestock production since the 1980s has driven the spread of E. coli bacteria carrying mobile colistin resistance (MCR) genes.
In this study, E. coli carrying an MCR gene (MCR-1) were exposed to AMPs known to play important roles in innate immunity in chickens, pigs, and humans. The bacteria were also tested for their susceptibility to human serum, which contains a complex cocktail of antimicrobial compounds, and for their ability to infect wax moth larvae (Galleria mellonella).
Key findings:
The results demonstrate that use of bacterial AMPs in agriculture can generate broad cross-resistance to the human innate immune response.
According to the researchers, cross-resistance to human AMPs is likely to be widespread, given that AMPs tend to have similar cellular targets and physico-chemical properties. Pigs and chickens in agriculture are already known to act as important reservoirs of colistin-resistant E. coli.
Lead researcher Professor Craig MacLean (Department of Biology, University of Oxford) said: ‘Our study clearly shows that anthropogenic use of AMPs such as colistin can drive the accidental evolution of resistance to the innate immune system of humans and animals. This has major implications for the design and use of therapeutic AMPs and suggests that resistant genes may be difficult to eradicate, even if AMP use in agriculture is withdrawn.’
He added: ‘AMPs have been advocated as a promising alternative to antibiotics for treating bacterial infections. Using AMPs in this way will lead to the evolution of AMP resistance in pathogenic bacteria. Our results provide strong evidence that we will need to properly assess the impacts of resistance to new therapeutic AMPs on bacterial virulence before they are used to treat patients. If not, we will run the risk of accidentally arming pathogenic bacteria against our own immune system.’
Cóilín Nunan, Scientific Adviser to the Alliance to Save Our Antibiotics (who were not involved in the study) said: ‘This new study shows that colistin resistance is probably even more dangerous than previously thought. It is astonishing that so many governments, like the UK’s, are refusing to ban colistin use in farming. It is also remarkable that the British government is still opposed to banning preventative mass medication of intensively farmed animals with antibiotics, even though the EU banned such use over a year ago.’
Dr Jessica Blair (University of Birmingham), Editor in Chief of NPJ Antimicrobials and Resistance (who was not involved in the study) said: ‘Antimicrobial peptides, including colistin, have been heralded as a potential part of the solution to the rise of multidrug-resistant infections. This study, however, suggests that resistance to these antimicrobials may have unintended consequences on the ability of pathogens to cause infection and survive within the host. This is particularly worrying because it suggests that E. coli carrying the MCR-1 gene may have a clear selective advantage even if the use of colistin is carefully controlled.’
Pramod K Jangir, Lois Ogunlana, Petra Szili, Marton Czikkely, Liam P Shaw, Emily J Stevens, Yu Yang, Qiue Yang, Yang Wang, Csaba Pál, Timothy R Walsh, Craig R MacLean. The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence. eLife, 2023; 12 DOI: 10.7554/eLife.84395
In a recent study published in the journal Clinical Microbiology and Infection, researchers in Spain, summarized the current understanding of the emergence and ecologic niches of Candida auris.
C. auris was first identified in a Japanese inpatient in 2009. The United States (US) Centers for Disease Control and Prevention (CDC) categorized the pathogen as an urgent threat. Moreover, C. auris has been designated as a fungal pathogenic species of critical concern by the World Health Organization (WHO) in their fungal priority list in October 2022.
Five clonally distinct clades of this fungus emerged independently and concurrently on three continents. Whole-genome sequencing of 47 isolates identified many single nucleotide polymorphisms (SNPs) with minimal intra-regional genetic diversity, suggesting a near-contemporary emergence in distinct geographic locations.
In the present study, the authors discussed the likely pathways of the emergence of C. auris and the role of inter-species transmission. In doing so, the study postulates that climate change has played a major role in high thermotolerant C. auris emergence. Thus, hypothesizing that climate change induced an environmental ancestor to become pathogenic through thermal adaptation.
Hypothetical emergence due to global warming
Global warming is proposed as the likely explanation for the independent and contemporary emergence of distinct C. auris clades. Few fungal species are pathogenic in endothermal animals and humans; very few fungi thrive at mammals’ high basal temperatures, creating a thermal barrier preventing infections.
Several reports suggest that increasing environmental temperatures due to climate change may result in the selection of thermotolerant fungal lineages that can circumvent the thermal barrier and infect/colonize endothermic animals.
One study showed that C. auris could grow at elevated temperatures than its close phylogenetic relatives. In addition, the remarkable halotolerance exhibited by this fungus suggested that it could have previously existed as an environmental species in wetlands/marshes.
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These ancestors might have become pathogens in humans after gaining thermotolerance due to climate change adaptation. Nevertheless, this hypothesis cannot explain the geographic dispersion of the independently evolved clades of C. auris.
Ecological niche(s) of C. auris
The first environmental isolates of C. auris were reported in 2021 from a salt marsh in the Andaman Islands and recently in Colombian estuaries. Notably, one of the isolates was less multidrug-resistant and less heat-tolerant.
It was also significantly different from clinical isolates suggesting a higher similarity to its wild ancestors from marine ecosystems.
C. auris also exhibits high-stress resistance, allowing for continued survival in stressful environments. This plasticity might contribute to its emergence and growing prevalence. Further, this fungus was detected in stored but not freshly pickled apples in India, suggesting a new human transmission pathway and a possible selection route for drug-resistant isolates in agriculture, storage, and supply chains.
Isolation from animal cultures or the environment has not been documented yet. Nonetheless, a study employing in silico DNA metabarcoding screened the internal transcribed spacer region in public datasets.
DNA metabarcoding identified partial matches in non-human sources, such as activated sludge, air dust, the ear canal of a dog with otitis, peanut fields, and the skin of newts. This provided evidence of the ubiquitous presence of the fungus in anthropogenic and natural environments.
One Health approach to understand and manage C. auris
One Health is an integrative, collaborative, multi/trans-disciplinary approach for sustainable balance and optimization of the health of humans, animals, and ecosystems.
Zoophilic fungi and, hypothetically, C. auris might have a dual life cycle wherein host, and environmental reservoirs may serve as durable sources of propagules. This might contribute to the global rise of emergent fungal diseases across continents.
Concluding remarks
The striking plasticity and the ability of C. auris to adapt to harsh environments could allow the fungus to thrive in sludge, wastewater, and fresh/marine waters.
Global warming, the impact of changes in the environment and human population, and indiscriminate antifungal use in agriculture might have led to C. auris evolving into a much more resistant/invasive pathogen that can infect/colonize endothermic animals.
Aquatic marine hosts could have spread primitive strains to humans. Therefore, adopting the One Health approach can help understand the relationship between animal/human health and ecological changes as factors in the emergence and transmission of fungal pathogens.
Microorganisms should be ‘weaponized’ to stave off conflicts across the globe, according to a team of eminent microbiologists.
The paper ‘Weaponising microbes for peace’ by Anand et al, outlines the ways in which microbes and microbial technologies can be used to tackle global and local challenges that could otherwise lead to conflict, but warns that these resources have been severely underexploited to date.
Professor Kenneth Timmis, Founding Editor of AMI journals Environmental Microbiology, Environmental Microbiology Reports and Microbial Biotechnology, says that worldwide deficits and asymmetries in basic resources and services considered to be human rights, such as drinking water, sanitation, healthy nutrition, access to basic healthcare and a clean environment, can lead to competition between peoples for limited resources, tensions, and in some cases conflicts.
There is an urgent need to reduce such deficits, to level up, and to assure provision of basic resources for all peoples. This will also remove some of the causes of conflicts. There is a wide range of powerful microbial technologies that can provide or contribute to this provision of such resources and services, but deployment of such technologies is seriously underexploited.”
Professor Kenneth Timmis, Founding Editor of AMI journals Environmental Microbiology, Environmental Microbiology Reports and Microbial Biotechnology
The paper then lists a series of ways in which microbial technologies can contribute to challenges such as food supply and security, sanitation and hygiene, healthcare, pollution, energy and heating, and mass migrations and overcrowding. For example, microbes are at the core of efforts to tackle pollution by bioremediation, replacing chemical methods of treating drinking water with metalloid conversion systems, and producing biofuels from wastes.
“There is now a desperate need for a determined effort by all relevant actors to widely deploy appropriate microbial technologies to reduce key deficits and asymmetries, particularly among the most vulnerable populations,” Professor Timmis said..
“Not only will this contribute to the improvement of humanitarian conditions and levelling up, and thereby to a reduction in tensions that may lead to conflicts, but also advance progress towards attainment of Sustainable Development Goals,” he said. .
“In this paper, we draw attention to the wide range of powerful microbial technologies that can be deployed for this purpose and how sustainability can be addressed at the same time. We must weaponise microbes for peace.”
The editorial is published in Microbial Biotechnology, an Applied Microbiology International publication, on March 7 2023.
Recommended actions to implement relevant microbial technology solutions to deficits
We need to urgently supply to communities lacking adequate levels of basic resources/services the infrastructure and know-how (capacity building), and funding for
use of agrobiologics to increase crop yields, by providing green nitrogen, stimulating plant growth, and combatting pathogens and pests,
exploitation of plant:microbe partnerships to improve soil health and implement regenerative agriculture,
creation of nutritious fermented food from locally available crops,
better use of microbes in the feed and food supply chains,
production of microbial food for humans and farm animals,
drinking water production and quality safeguarding,
waste treatment with resource recovery,
creation of modular DIY digital medical centres,
production of vaccines and medicines,
bioremediation and biorestoration of the environment in general and natural ecosystems in particular, to create healthier habitats and promote biodiversity
reduction of greenhouse gas production and capturing carbon,
production of biofuels,
creation of local employment opportunities associated with the above,
development of transdisciplinary approaches, using chemistry-related, computation technologies, psychology-related and other approaches that are synergistic to microbial solutions and
A groundbreaking Tel Aviv University study has discovered about 100,000 new types of previously unknown viruses – a ninefold increase in the number of RNA viruses known to science until now. These viruses were discovered in global environmental data from soil samples, oceans, lakes, and other ecosystems. This discovery may aid in the development of anti-microbial drugs and protect against agriculturally harmful fungi and parasites.
Doctoral student Uri Neri led the study under the guidance of Prof. Uri Gophna of the Shmunis School of Biomedicine and Cancer Research in the Wise Faculty of Life Sciences at Tel Aviv University. The research was conducted in collaboration with the US-based research bodies NIH and JGI, as well as the Pasteur Institute in France. The study was published in the prestigious journal Cell and comprised data collected by more than a hundred scientists worldwide.
Viruses are genetic parasites, meaning they must infect a living cell to replicate their genetic information, produce new viruses, and complete their infection cycle. Some viruses are disease-causing agents that can cause harm to humans (such as the coronavirus). Still, the vast majority of viruses do not harm us and infect bacterial cells – some even live inside our bodies without us being aware.
Uri Neri says that the study used new computational technologies to mine genetic information from thousands of different sampling points worldwide (oceans, soil, sewage, geysers, etc.). The researchers developed a sophisticated computational tool that distinguished between the genetic material of RNA viruses and that of the hosts and used it to analyze the big data. The discovery allowed the researchers to reconstruct how the viruses underwent diverse acclimation processes throughout their evolutionary development to adapt to different hosts.
In analyzing their findings, the researchers identified viruses suspected of infecting various pathogenic microorganisms, thus opening up the possibility of using viruses to control them.
“The system we developed makes it possible to perform in-depth evolutionary analyses and to understand how the various RNA viruses have developed throughout evolutionary history. One of the key questions in microbiology is how and why viruses transfer genes between them. We identified a number of cases in which such gene exchanges enabled viruses to infect new organisms. Furthermore, compared to DNA viruses, the diversity and roles of RNA viruses in microbial ecosystems are not well understood. In our study, we found that RNA viruses are not unusual in the evolutionary landscape and, in fact, that in some aspects, they are not that different from DNA viruses. This opens the door for future research and a better understanding of how viruses can be harnessed for use in medicine and agriculture,” said Prof. Gophna
Genetics & Genomics eBook
Compilation of the top interviews, articles, and news in the last year.
Overall, the results show a large expansion of the diversity of Orthornavira, especially that of RNA viruses associated with bacteria. In addition, they introduce relatively minor changes to the latest taxonomic scheme, supporting its overall robustness. Furthermore, RNA viruses are predicted to have multiple protein functions. This work generated a large number of sequences and derivatives, which can be accessed through the companion website (riboviria.org) or via the Zenodo deposit. Using this resource, researchers can gain meaningful context when describing new RNA viruses in future research. For example, by gaining insights into specific viral lineages’ ecological distributions or annotating their specific protein domains. Further, this resource may assist researchers in identifying key RNA virus genomes that can be further characterized experimentally.
Thanks to high-throughput sequencing technologies, shotgun metagenomic methods were made possible and had effectively transformed microbiology. Today, advances in both short- and long-read technologies are overcoming many of the previous challenges affecting metagenomic profiling, especially of highly complex samples and environment.
Researchers from France’s National Research Institute for Agriculture, Food, and Environment (INRAE) examined the performance of seven short- and long-read sequencing platforms in analyzing high-complexity metagenomic samples. The study, published in the Nature Portfolio journal Scientific Data, ran mock samples between 2018 and 2019 on various mainstream sequencers at the time, including MGI’s DNBSEQ-T7* and DNBSEQ-G400*.
Within this wide range of sequencing technologies tested, DNBSEQ-T7* was recognized for its ultra-high throughput and excellent accuracy. “We were surprised by the T7’s performance*,” said senior author Mathieu Almeida, a research fellow at INRAE.
It provides ultra-deep sequencing in a single run with similar low error rate compared to the other platforms, making it at the time of our study one of the most affordable technologies for metagenomic sequencing.”
Mathieu Almeida, Senior Author and Research Fellow, INRAE
In the study, three uneven synthetic microbial communities were constructed, consisting of up to 87 genomic microbial strains DNAs each and spanning 29 bacterial and archaeal phyla. They represented some of the most complex and diverse communities used for sequencing technology comparisons. The mock1 (71 strains) was sequenced using all platforms, mock2 (64 strains) was additionally sequenced to estimate the impact of various microbial richness, while MGI’s platforms were not performed on mock3.
To assess the impact of sequencing depth, the team ran a subsampling analysis and compared observed and theoretical genome abundances across samples at multiple depth from 10,000 to 1 million reads. Overall, Spearman rank correlations for all platforms were high at above 0.9 when mapping at least 100,000 reads. Among them, the correlations of T7* and G400* were the best in mock1 and remained excellent in mock2.
Overall comparison between observed and excepted mock compositions for each platform. Image Credit: MGI
In addition, differential analysis between observed and excepted species abundances was performed in mock1. Results showed that over or under abundance estimation for most genomes had little to do with the sequencing platform, read length, taxonomy, GC-content, genome size and genome completeness, even at a low depth of 500,000 reads. In fact, most genomes were accurately estimated on all sequencers, with the observed normalized abundances generated by T7* charting very close to the excepted values.
Differential plot between observed and excepted species abundances in mock1. Image Credit: MGI
Based on performance analyses of the different sequencers, the study formed a microbial metagenomic sequencing benchmarking database, providing researchers and scientists a comprehensive and authentic reference for sequencing platform selection. In particular, the findings demonstrated the promising value of MGI’s DNBSEQ-T7* in metagenomic sequencing.
Boasting high stability and accuracy as shown in the data, combined with outstanding throughput, T7* makes a strong platform for the identification of species and functional genes in highly complex microbial communities. Its upgraded biochemical, fluidics, and optical systems are not only making sequencing more efficient and productive, but also continuing to support research into the structure and diversity of microbial communities.
*Unless otherwise informed, StandardMPS and CoolMPS sequencing reagents, and sequencers for use with such reagents are not available in Germany, Spain, UK, Sweden, Belgium, Italy, Finland, Czech Republic, Switzerland, Portugal, Austria, and Romania. Unless otherwise informed, StandardMPS sequencing reagents, and sequencers for use with such reagents are not available in Hong Kong. No purchase orders for StandardMPS products will be accepted in the USA until after January 1, 2023.
Thanks to high-throughput sequencing technologies, shotgun metagenomic methods were made possible and had effectively transformed microbiology. Today, advances in both short- and long-read technologies are overcoming many of the previous challenges affecting metagenomic profiling, especially of highly complex samples and environment.
Researchers from France’s National Research Institute for Agriculture, Food, and Environment (INRAE) examined the performance of seven short- and long-read sequencing platforms in analyzing high-complexity metagenomic samples. The study, published in the Nature Portfolio journal Scientific Data, ran mock samples between 2018 and 2019 on various mainstream sequencers at the time, including MGI’s DNBSEQ-T7* and DNBSEQ-G400*.
Within this wide range of sequencing technologies tested, DNBSEQ-T7* was recognized for its ultra-high throughput and excellent accuracy. “We were surprised by the T7’s performance,” said senior author Mathieu Almeida, a research fellow at INRAE. “It provides ultra-deep sequencing in a single run with similar low error rate compared to the other platforms, making it at the time of our study one of the most affordable technologies for metagenomic sequencing.”
In the study, three uneven synthetic microbial communities were constructed, consisting of up to 87 genomic microbial strains DNAs each and spanning 29 bacterial and archaeal phyla. They represented some of the most complex and diverse communities used for sequencing technology comparisons. The mock1 (71 strains) was sequenced using all platforms, mock2 (64 strains) was additionally sequenced to estimate the impact of various microbial richness, while MGI’s platforms were not performed on mock3.
Genetics & Genomics eBook
Compilation of the top interviews, articles, and news in the last year.
To assess the impact of sequencing depth, the team ran a subsampling analysis and compared observed and theoretical genome abundances across samples at multiple depth from 10,000 to 1 million reads. Overall, Spearman rank correlations for all platforms were high at above 0.9 when mapping at least 100,000 reads. Among them, the correlations of T7* and G400* were the best in mock1 and remained excellent in mock2.
In addition, differential analysis between observed and excepted species abundances was performed in mock1. Results showed that over or under abundance estimation for most genomes had little to do with the sequencing platform, read length, taxonomy, GC-content, genome size and genome completeness, even at a low depth of 500,000 reads. In fact, most genomes were accurately estimated on all sequencers, with the observed normalized abundances generated by T7* charting very close to the excepted values.
Based on performance analyses of the different sequencers, the study formed a microbial metagenomic sequencing benchmarking database, providing researchers and scientists a comprehensive and authentic reference for sequencing platform selection. In particular, the findings demonstrated the promising value of MGI’s DNBSEQ-T7* in metagenomic sequencing.
Boasting high stability and accuracy as shown in the data, combined with outstanding throughput, T7* makes a strong platform for the identification of species and functional genes in highly complex microbial communities. Its upgraded biochemical, fluidics, and optical systems are not only making sequencing more efficient and productive, but also continuing to support research into the structure and diversity of microbial communities.
Meslier, V., et al. (2022) Benchmarking second and third-generation sequencing platforms for microbial metagenomics. Scientific Data.doi.org/10.1038/s41597-022-01762-z.
Microbiome: From Research and Innovation to Market
