Tag Archives: Plasmid

New tool shows early promise to help reduce the spread of antimicrobial resistance

A new tool which could help reduce the spread of antimicrobial resistance is showing early promise, through exploiting a bacterial immune system as a gene editing tool.

Antimicrobial resistance is a major global threat, with nearly five million deaths annually resulting from antibiotics failing to treat infection, according to the World Health Organisation.

Bacteria often develop resistance when resistant genes are transported between hosts. One way that this occurs is via plasmids – circular strands of DNA, which can spread easily between bacteria, and swiftly replicate. This can occur in our bodies, and in environmental settings, such as waterways.

The Exeter team harnessed the CRISPR-Cas gene editing system, which can target specific sequences of DNA, and cuts through them when they are encountered. The researchers engineered a plasmid which can specifically target the resistance gene for Gentamicin – a commonly used antibiotic.

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In laboratory experiments, the new research, published in Microbiology, found that the plasmid protected its host cell from developing resistance. Furthermore, researchers found that the plasmid effectively targeted antimicrobial-resistant genes in hosts to which it transferred, reversing their resistance.

Antimicrobial resistance threatens to outstrip covid in terms of the number of global deaths. We urgently need new ways to stop resistance spreading between hosts. Our technology is showing early promise to eliminate resistance in a wide range of different bacteria. Our next step is to conduct experiments in more complex microbial communities. We hope one day it could be a way to reduce the spread of antimicrobial resistance in environments such as sewage treatment plants, which we know are breeding grounds for resistance.”

David Walker-Sünderhauf, Lead Author, University of Exeter

The research is supported by GW4, the Medical Research Council, the Lister Institute, and JPI-AMR.

Source:
Journal reference:

Walker-Sünderhauf, D., et al. (2023) Removal of AMR plasmids using a mobile, broad host-range, CRISPR-Cas9 delivery tool. Microbiology. doi.org/10.1099/mic.0.001334.

Genetically-engineered probiotic could be a new way to reduce alcohol-induced health problems

Excessive alcohol consumption leads to painful hangovers and accompanying headaches, fatigue, and nausea. Drinking alcohol has also been linked to a raft of health problems in the human body, including heart disease, cirrhosis, and immune deficiency. One way to avoid those consequences would be to drink less, but researchers in China have introduced another way to mitigate hangovers and other adverse outcomes -; a genetically-engineered probiotic.

In a paper published this week in Microbiology Spectrum, the researchers described their approach and reported that in experiments on mice, the treatment reduced alcohol absorption, prolonged alcohol tolerance, and shortened the animals’ recovery time after exposure to alcohol. The probiotic hasn’t yet been tested on humans, but the authors predicted that if it confers the same benefits, it could present a new way to reduce alcohol-induced health problems, and liver problems in general.

Meng Dong, Ph.D, at the Chinese Academy of Science’s Institute of Zoology, who worked on the study, noted that clinical applications may extend beyond alcohol-related conditions. “We believe that genetically engineered probiotics will provide new ideas for the treatment of liver diseases,” she said.

The human body primarily uses forms of an enzyme called alcohol dehydrogenase, or ADH, to metabolize alcohol. But some variants are more effective than others: Some studies have found that a form called ADH1B, found primarily in East Asian and Polynesian populations, is 100 times more active than other variants. Previous studies on mice have shown that viral vectors genetically engineered to express ADH1B can accelerate the breakdown of alcohol, but that approach hasn’t been shown to be safe in humans.

Motivated by those findings, Dong and her colleagues looked for a safer delivery method, focusing on the probiotic Lactococcus lactis, a bacterium often used in fermentation. They used molecular cloning to introduce the gene for human ADH1B into a bacterial plasmid, which was then introduced into a strain of L. lactis. Lab tests confirmed that the probiotic secreted the enzyme. The researchers encapsulated the probiotic to ensure it would survive against stomach acid, then tested it on 3 groups of 5 mice, each exposed to different levels of alcohol.

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Untreated mice showed signs of drunkenness 20 minutes after exposure to alcohol. When the mice were placed on their backs, for example, they were unable to get back on their feet. But in the group that received a probiotic that expressed human ADH1B, half the mice were still able to turn themselves over an hour after alcohol exposure. A quarter never lost their ability to turn themselves over.

Further tests showed that 2 hours after exposure, blood alcohol levels in the control group continued to rise, while those in the probiotic-treated mice had begun to fall. In addition, the researchers found that treated mice showed lower levels of lipids and triglycerides in their livers, suggesting that the probiotic could alleviate alcohol-related damage to that organ.

The next step, Dong said, is to investigate whether the potential therapeutic effect of the modified probiotic extends to humans.

We are excited about the improvement of recombinant probiotics in acute alcohol-induced liver and intestinal damage.”

Meng Dong, Ph.D, Chinese Academy of Science’s Institute of Zoology

Source:
Journal reference:

Jiang, X., et al. (2023) Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice. Microbiology Spectrum. doi.org/10.1128/spectrum.04294-22.

Bacterial outer membrane vesicles: utility as vaccines and novel engineering approaches

In an article published in Frontiers in Microbiology, scientists have described the utility of gram-negative bacteria-derived outer membrane vesicles as vaccines and methods to expand their applications.

Study: Outer membrane vesicles: A bacterial-derived vaccination system. Image Credit: Maxx-Studio/Shutterstock
Study: Outer membrane vesicles: A bacterial-derived vaccination system. Image Credit: Maxx-Studio/Shutterstock

Background

Outer membrane vesicles (OMVs) are spherical lipid nanoparticles with a diameter of 20-300 nm. These vesicles are derived from the cell membrane of Gram-negative bacteria and are composed of bacterial proteins, lipids, nucleic acids, and other components.

OMVs derived from pathogenic or non-pathogenic bacteria play an essential role in bacterial pathogenesis, cell-to-cell communication, horizontal gene transfer, quorum sensing, and maintaining bacterial fitness. However, as a non-replicative component, OMVs cannot induce disease pathogenesis independently.  

Bacterial proteins and glycans make OMVs a potent immunogenic component that can be used as adjuvants to induce host immune response. Because of this property, OMVs are considered potential candidates for vaccine development.

Isolation of OMVs

Gram-negative bacteria release OMVs during growth or in stressful conditions. However, such spontaneous OMVs are released in low quantities and, thus, cannot be used for large-scale vaccine production.

Several strategies have been developed to increase OMV production. Sonication, vortexing, or EDTA-mediated extraction have been applied to mechanically disrupt the bacterial membrane, leading to the release of OMVs.

OMVs extracted by EDTA closely relate to the native bacterial membrane and induce comparable immune responses. In contrast, sonication and vortexing increase the amount of non-membrane components in the final product, resulting in increased antigenicity and reduced safety.

Detergent-based extraction is another well-documented method that produces OMVs with reduced levels of lipopolysaccharides (LPS), which are bacterial toxins. Despite reducing the risk of toxicity, this process leads to the loss of many bacterial proteins and lipoproteins, which in turn results in the suppression of OMV-stimulated immune responses.

Manipulating certain bacterial genes can increase vesiculation and, thus, can produce high levels of genetically-modified OMVs. The genes encoding bacterial lipoproteins Lpp and NlpI and the outer membrane protein OmpA are the major targets for genetic manipulation.

Heterologous OMVs

Non-pathogenic bacterial strains can express heterologous proteins to reduce toxicity and improve the immunogenicity of OMVs.

A protein of interest can be fused with a bacterial transmembrane protein, and the resulting plasmid can be introduced into the bacterial strain, which will subsequently produce recombinant OMVs expressing the desired protein on the surface.

Another potential strategy for expressing heterologous proteins is glycoengineering of the LPS O antigen. Glycosylated OMVs can be produced by expressing the O antigen gene of a pathogen in a non-pathogenic O-antigen mutant strain of bacteria.

OMV-induced immune response

The pathogen-associated molecular patterns present on the OMV outer membrane activate the pattern recognition receptors on the host cells, leading to the activation of innate immune signaling and the release of proinflammatory cytokines. The engulfment of OMVs by innate immune cells induces adaptive immune responses.

LPS acts as an adjuvant to induce an effective host immune response to the bacterial antigen expressed on the OMV surface. However, overexpression of LPS can lead to overstimulation of immune responses and induction of systemic toxic shock. Detergent-based preparations or genetic manipulations can be used to reduce the level of highly reactive LPS on the OMV surface.

OMV-based vaccines

OMVs expressing desired antigens can be administered into the body through various routes, including oral/intranasal, intramuscular, subcutaneous, intraperitoneal, and intradermal. It has recently been shown that OMV expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces robust immune responses in hamsters when administered intranasally.

Two clinically-approved OMV vaccines, VA-MENGOC-BC™ and Bexsero™, are currently available against the invasive N. meningitidis serogroup B strain. The PorA protein expressed by this bacterium is highly variable between strains. The OMVs derived from the meningitis-causing strain have been used successfully to develop vaccines against this particular bacterial strain.

Many OMV vaccines are currently under development. These vaccine candidates have been designed to target N. gonorrhoeae, Shigella spp., Salmonella spp., extraintestinal pathogenic E. coli (EXPEC), V. cholerae, M. tuberculosis, and non-typeable H. influenzae.    

Besides anti-bacterial vaccines, OMVs have been used to produce vaccines against viruses, including influenza virus and coronavirus. Tumor-targeted OMVs containing therapeutic siRNA or tumor antigens have also been developed as therapeutic cancer vaccines.

Journal reference:

World Antimicrobial Awareness Week 2022: What is the burden of antimicrobial resistance?

Thought LeadersDr. Tomislav MeštrovićAffiliate Associate ProfessorUniversity of WashingtonAs part of World Antimicrobial Resistance Week 2022, News-Medical speaks to Dr. Tomislav Meštrović about his new research discussing the burden of bacterial antimicrobial resistance in the WHO European region, as well as about how we can prevent antimicrobial resistance together.

Please can you introduce yourself and tell us about your background and interest in antimicrobial resistance (AMR)?

Before participating in the research on the global burden of antimicrobial resistance (AMR), as a medical doctor, clinical microbiologist, and biomedical scientist, I was a part of relevant research endeavors on antibiotic resistance in my home country Croatia – such as a nationwide study on extended-spectrum beta-lactamases and plasmid diversity in urinary Escherichia coli isolates, as well as describing the emergence of multidrug-resistant Proteus mirabilis in long-term care facilities.

Since my Ph.D. thesis was on addressing AMR in the most common sexually transmitted bacterial agent, Chlamydia trachomatis, I was also a part of the team that aimed to standardize the method for laboratory susceptibility testing of chlamydiae by using both special cell culture and direct molecular-based monitoring, which was published in one methodological textbook.

Therefore, I would say AMR in different microorganisms was always my passion – from the diagnostic standpoint and the therapeutic one. More specifically, I was also involved in certain aspects of drug research, such as proposing a novel dual antagonist to prevent and treat urinary Escherichia coli infections and the usage of liposomal encapsulation to increase the efficacy of azithromycin against Chlamydia trachomatis. The latter technology gained a lot of prominence when liposome-based mRNA COVID-19 vaccines entered the market, so it is no wonder that we tried to capitalize on the positive aspects of such an approach.        

Regarding my other professional positions, I am also a Secretary General of the Croatian Society for Clinical Microbiology, Executive Committee Member of the ESCMID study group for Mycoplasma and Chlamydia Infections, and External Affairs Committee Member of the Society for Healthcare Epidemiology of America (SHEA). I have several leadership roles in the American Society for Microbiology (ASM), where I organized conference sessions on antibiotic resistance, such as the Track Hub Session for ASM Microbe, “The global scenario of antimicrobial resistance: do developing and developed countries share the same threats?”. Finally, I am very invested in science communication. As one of the writers for News-Medical, I have written several pieces on the topic of antimicrobial resistance and many other topics.

AMR is a threat to not only humans but also animals, plants, and the environment. Can you tell us more about what exactly AMR is?

Antimicrobial resistance (AMR) is regarded as one of the predominant and most salient public health issues of the 21st century, as it threatens the effective treatment and prevention of an ever-growing range of infections caused by bacteria, viruses, fungi, and parasites. In other words, these groups of microorganisms are no longer susceptible to the common medical agents used to treat them, and the issue is particularly serious and urgent in bacteria. This is an evolving issue that took place over several decades, resulting in frequent pathogenic bacteria harboring some type of resistance to each new antibiotic coming to the market. This means there is an urgent call for action to avoid a global crisis in health care when we can lose the ability to perform surgeries and other types of quotidian medical procedures.

In an attempt to define AMR, we can say that this is a natural phenomenon arising when microorganisms are exposed to antimicrobials or antibiotics. Under such selective pressure, susceptible bacteria are inhibited or killed, whereas those that are naturally (or intrinsically) resistant or those with antibiotic-resistant traits have a much greater chance of surviving and multiplying. The issue arises not only as a result of the overuse of antimicrobial agents but also when they are used inappropriately (such as inadequate drug choices, faulty dosing regimens, and/or low compliance to relevant treatment guidelines). All of this can have a compounding effect and contribute to the rise of antibiotic resistance.

During the last few years, the importance of animal reservoirs and the environment in spreading AMR has been widely recognized. In the past several decades, we have witnessed an increased awareness of the potential problems that resistance among food-producing animals could have on human health. In addition, the soil is regarded as a reservoir of AMR genes since most antibiotics are derived from soil microorganisms that are intrinsically resistant to the antibiotics produced. Finally, water potentially contaminated with organic fertilizers and fecal microorganisms may disseminate resistant bacteria in the soil and is considered a principal way of bacterial propagation between various environmental compartments.

Given the dangers of AMR and the slogan of World Antimicrobial Awareness Week – ‘Antimicrobials: Handle with Care,’ why is it crucial to handle antimicrobials with care?

Judicious and careful use of antimicrobial agents is one of the pillars of successfully diminishing the threat of AMR. In the clinical milieu, there is an important concept of antimicrobial stewardship that refers to a set of coordinated strategies for improving patient care and outcomes by instituting optimal therapy, minimizing collateral damage by reducing antimicrobial usage (which translates to lower resistance rates), and lowering the price of antimicrobials. This concept is also amenable to global implementation to help control AMR by increasing awareness of the public and educating healthcare professionals on the prudent use of antimicrobials.

In the hospital setting, antimicrobial stewardship programs and infection control measures are of utmost importance to prevent the emergence and transmission of antibiotic-resistance microorganisms and preserve the effectiveness of currently available antimicrobial drugs. Hence, multidisciplinary teams of experts (such as infectious disease specialists, medical microbiologists, and clinical pharmacists) participate in such endeavors. Moreover, as the ongoing COVID-19 pandemic can lead to the increased indiscriminate usage of antimicrobials (which was particularly the case in the early days of SARS-CoV-2 spread), handling antibiotics with care can result in lower bacterial resistance and, subsequently, a lower death toll.

Nevertheless, the antimicrobial stewardship concept has to be extended to family doctors in the community, where there is often a very high consumption of antibiotics. Relevant public health actions that are needed to reduce inappropriate antimicrobial prescriptions and antibiotic misuse should consider adequate information campaigns for the consumers, training of healthcare professionals, enhanced diagnostics to improve treatment decisions, the development of treatment guidelines, as well as regular prescription audits. In a nutshell, different healthcare organizations should strive to make coordinated efforts to institute new policies and put more emphasis on antimicrobial stewardship in professional curricula.

Image Credit: dturphoto/ShutterstockImage Credit: dturphoto/Shutterstock

You recently published research concerning the burden of bacterial antimicrobial resistance in the WHO European region. Can you tell us more about this study and the results you identified?

To our knowledge, this new study brings the most comprehensive analysis of the AMR burden in the WHO European region, and our estimates span across 53 countries, 23 bacterial pathogens, and 88 pathogen–drug combinations in 2019. There are several advances in comparison to previous work on this topic, primarily in scope (as not only the European Union is included, but all countries of the WHO European region), as well as in the number of included pathogen-drug combinations.

Furthermore, we used major methodological innovations that were first identified in the 2019 global burden of bacterial AMR study. The magnitude of the problem was described with the use of two scenarios, which means we provided estimates for both deaths directly caused by AMR (attributable mortality) and deaths that occurred from a drug-resistant infection, but for which AMR may or may not have been the cause (associated mortality).

Finally, our study allows comparisons with other causes of death since it builds on estimates of disease incidence, prevalence, and mortality from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019.

And results were striking. By identifying more than half a million deaths associated with AMR and more than 130 thousand deaths attributable to AMR, we have shown that antibiotic resistance is a considerable and potentially neglected problem in the WHO European region as a whole, with evident differences between subregions and specific countries. The largest fatal burden of AMR in the region came from bloodstream infections, followed by intra-abdominal infections and respiratory infections. The leading pathogens that we identified were (in descending order of death) Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterococcus faecium.

Such estimates of the impact of AMR on morbidity and mortality are crucial for informing public health investment decisions for each country in this region. Furthermore, highlighting specific pathogens and pathogen–drug combinations with the highest estimated burden – which we showed were methicillin-resistant Staphylococcus aureus (MRSA) and aminopenicillin-resistant Escherichia coli – might specifically inform policy targets and policy design. Our results emphasize that the most effective way to address AMR in this region will necessitate targeted efforts and investments, together with continuous outcome-based research endeavors.

Study: fizkes/ShutterstockStudy: fizkes/Shutterstock

What do you believe are some of the challenges with approximating the magnitude of the AMR crisis and its downstream effect on human health?

There are indeed many challenges with this type of complex estimation process, and the biggest one is definitely data scarcity, as the availability of data on AMR can differ from one country to the next. This is not the only problem with our study but is universal for all research projects that aim to assess the burden of AMR. We also acknowledge that the effect of resistance on mortality may differ across locations, which can be pertinent when we pursue a global estimation of the AMR crisis.

More specifically, certain locations might not be well-suited to treat susceptible infections, which means that the effect of resistance is minimized; conversely, other locations might not have access to second-line antimicrobials; thus, the effect of resistance is magnified. It is also possible that the relative risk of death attributable to resistance can be different across anatomical sites of infection due to variable antibiotic penetrance.

Moreover, countries with low socio-demographic index (which is a summary measure that combines information on the education, economy, and fertility rate) might have much less stringent surveillance systems, as well as insufficient laboratory support – potentially resulting in an underestimation of attributable and associated AMR mortality globally and the countries of the WHO European Region. Nonetheless, our estimates are informed by data from all countries included in the study. When data for a specific country were lacking, estimates and model building relied on regional patterns, co-variates, and out-of-sample predictive validity.

Despite these limitations, our analysis reflects the widest and presently best available range of data, as well as the use of models that have been developed and implemented specifically for incorporating disparate data sources for the Global Burden of Disease analysis. We are in agreement with other studies that highlight and underscore critical data gaps on resistant organisms in certain parts of the world; therefore, solving this problem which will be extremely important in the future to fine-tune our estimates additionally.

WHO: What is antimicrobial resistance (AMR)?

The specific theme of World Antimicrobial Awareness Week (WAAW) 2022 is ‘Preventing antimicrobial resistance together.’ What does this theme mean to you personally, and how do you believe we can take steps toward this goal?

It is without any doubt that manifold joint efforts from healthcare workers (acting as prescribers) and patients to policymakers and international regulators are necessary to stand a chance against the global spread of antibiotic resistance. In other words, different stakeholders have to join forces in order to tackle this issue from many angles, as no single action will provide an acceptable solution in isolation.

Also, this issue is a truly global problem. Together with rational and prudent usage of currently available antimicrobial drugs and the introduction of antibiotics where there is a lack of them, the development of new and effective compounds, as well as the introduction of new diagnostic approaches, are all recognized as urgent priorities.

Governments should introduce several essential processes to inspire change by all stakeholders related to AMR, as appropriately described within the WHO policy package for combating drug resistance. More specifically, this policy package refers to a national plan that strives to be comprehensive, engages civil societies, and insists on the accountability of everyone involved. Also, strengthened surveillance systems, improved laboratory capacity, wide access to essential medicines of sufficient quality, regulated use of antibiotics, the emphasis on infection prevention and control, as well as promotion of innovations will be crucial in the near future. There has to be a commitment to a rather high level of human health protection.

How do you believe that different sectors, for example, healthcare, animal care, farming, and agriculture, can work collaboratively to help curb AMR?

Our quest against AMR should be addressed through the lens of a One Health approach. This means more stringent infection prevention/control in healthcare facilities, food industry premises, and farms, as well as insisting on best practices in agriculture, clean water, sanitation and waste management. A set of diverse but coordinated strategies against antibiotic resistance should be implemented, taking into account the type of pathogen (either human or zoonotic), the setting (healthcare or the community) and possibly other specific factors contributing to the emergence of resistance.

In veterinary medicine, the required interventions consist in enforcing regulations for improved surveillance and monitoring, governing the use of antimicrobials in food-producing animals, and decreasing the need for antibiotics through improved animal husbandry. Naturally, more research is needed to elucidate the exact pathways of transmission of resistant microbial agents between animals and humans (but also their subsequent impact). There is a need to adequately implement legislation if we are to achieve long-lasting effects.

In addition, innovative approaches are needed for the development of new antibiotics and other products to limit AMR. There is a shortage of new antibiotics in the pipeline and few incentives for the industry to invest in research and development in this field. Research into digital technologies and eHealth solutions has to be strengthened to improve prescription practices, care solutions, and overall awareness of this issue. All of this necessitates a well-designed roadmap to orchestrate further collaboration efforts between governments, industry, and non-governmental organizations.

Image Credit: AnaLysiSStudiO/ShutterstockImage Credit: AnaLysiSStudiO/Shutterstock

What are the next steps for you and your research? Do you have any exciting projects coming up?

The Global Research on AntiMicrobial resistance (GRAM) Project will definitely continue to be one of the most important global projects in years to come. Assessing the burden of bacterial antimicrobial resistance in the WHO European region in 2019 was our first regional endeavor, which will be followed by research publications covering other regions of the world. We believe it is of utmost importance to obtain a full picture of this pressing issue not only on a global but also on a regional and country level. In the future, one of the goals is to pursue a time-series analysis of the AMR burden through the years, which will be helpful in forecasting, preparedness planning, and key policy decisions.

Furthermore, we have already mentioned how the animal and environmental sectors present a plethora of opportunities for resistance to evolve and be introduced into human populations. Therefore, we believe it will be important to assess data gaps and links between animal and human resistance in one of our future projects. Our goal is also to assess significant indirect effects of AMR, such as the effect of AMR on antibiotic prophylaxis in transplant recipients or for the prevention of surgical site infections. One of the salient goals is to assess AMR in the context of health equity, particularly considering the results from the paper on the global burden of AMR.

Finally, there is a need to prioritize the improved collection of high-quality AMR data in both the human and animal sectors, as well as the environment, in order to improve all our future estimation processes. One of our goals is to facilitate data and resource sharing between countries to improve policy-making and capacity building. Finally, continuously broadening both the quantity and quality of data acquisition worldwide will allow us to monitor levels of resistance much more effectively and course-correct action where needed. We are confident that our data-driven approach will result in even more stringent estimates and help in tackling this enormous challenge.

Where can readers find more information?

About Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is an Associate Professor at the University North in Croatia and an Affiliate Associate Professor at the Institute for Health Metrics and Evaluation (IHME) and the Department of Health Metrics Sciences of the University of Washington. He finished his medical and doctoral training at the University of Zagreb School of Medicine (Croatia), his MPH at the London School of Hygiene and Tropical medicine of the University of London (United Kingdom), and his MBA in International Healthcare Management at the Frankfurt School of Finance & Management (Germany). He is a board-certified clinical microbiology and sexual medicine specialist, with an additional one-year training in clinical research from Harvard Medical School.

His primary research interest with IHME is the public health significance and impact of antimicrobial resistance (AMR) within the Global Burden of Antimicrobial Resistance (GRAM) project, working in the AMR research team led by Professor Mohsen Naghavi. He joined this group as a Fulbright Visiting Scholar during the academic year 2021/2022, and was a lead author on the comprehensive assessment of AMR burden in the WHO European Region. Alongside his ongoing work in antibiotic resistance, he participates in other IHME-led and GBD-related projects, providing expertise for many pivotal global and public health research questions (particularly those in relation to infectious diseases). He is also a member of the WHO/HIFA Working Group Member on Learning for Quality Health Services, which is a part of the WHO Global Learning Laboratory (GLL) for Quality Universal Health Coverage (UHC).

IHME was established at the University of Washington in Seattle in 2007. Its mission is to deliver to the world timely, relevant, and scientifically valid evidence to improve health policy and practice.

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One of the most significant consequences of climate change is the greenhouse gases generated from the microbial decomposition …

One of the most significant consequences of climate change is the greenhouse gases generated from the microbial decomposition of organic matter in thawing permafrost soil. Permafrost refers to ground soil frozen at 0℃ or lower, year after year. Permafrost regions of the Earth are mostly found in the north and south poles. During summer, some thawing of the permafrost landscape is considered normal, but with climate change, thawing has increased annually.

Studies of permafrost soil have previously identified ancient bacteria, viruses, fungi, and even protozoans that can potentially become infectious after several years of being frozen. Apart from identification, the global impact of the microbial composition of permafrost on human health remains largely undetermined. 

More recently, DNA was isolated from soil samples in the carbon-rich Yedoma permafrost of Siberia. The Yedoma permafrost is known to have preserved animal remains like mammoths and ancient microbial content. An international team of scientists from Russia and Germany conducted a ‘metagenomic’ analysis of various soil samples from the Yedoma permafrost, which involves the detailed characterization of all DNA extracted from multiple soil samples. Their studies from the Yedoma soils have identified bacterial genes from several bacterial species with no specific correlation to the age of the permafrost. Interestingly, a high frequency of the beta-lactamase gene was detected within the identified bacterial genomes. What does this mean? The DNA samples belong to diverse bacterial species, and all carry the gene for the enzyme beta-lactamase. Beta-lactamases are enzymes that cause the inactivation of penicillin-derived antibiotics, thereby conferring antibiotic resistance to the bacteria carrying them (in their genome or plasmids). 

Active microbial life has been discovered in the arctic before. But the discovery of bacterial DNA, a large proportion of which carries antibiotic resistance, is unexpected. This finding is even more perplexing to scientists because these soils have remained far removed from human civilization that have heavy antibiotic usage. The acquisition of antibiotic resistance is technically possible outside a clinical setting. Bacteria acquire genes from their environment all the time. However, the potential danger of thawing permafrost and the release of bacterial DNA offering antibiotic resistance is concerning.

Antimicrobial resistance (AMR) is a global health issue that severely challenges our ability to treat bacterial infections effectively. Tracking and early identification of AMR in clinical settings is key to reducing its spread. The discovery of antibiotic resistance in permafrost does not directly affect clinical care today but has implications for the future of AMR, especially with a rising concern about climate change. 


Anusha Naganathan