Discovery Alert

Researchers from the Catalonian Institute of Bioengineering and the Seville Chemical Research Institute have described a new method for the transmission of electrons between proteins that refutes the evidence from experiments until now. This process, involved in the generation of energy in both animal and plant cells, will permit better understanding of the behaviour of proteins in the cells, as well as giving a deeper understanding of the energy dysfunctions that cause diseases. The findings were published in the review Nature Communications. Learn More

In an advance that could lead to new treatments for lung disease, MIT researchers have now designed an inhalable form of mRNA. This aerosol could be administered directly to the lungs to help treat diseases such as cystic fibrosis, the researchers say. The researchers showed that they could induce lung cells in mice to produce a target protein -- in this case, a bioluminescent protein. If the same success rate can be achieved with therapeutic proteins, that could be high enough to treat many lung diseases, the researchers say. Asha Patel, a former MIT postdoc who is now an assistant professor at Imperial College London, is the lead author of the paper, which appears in the January 4th, 2019 issue of the journal Advanced Materials. Learn More

Proteins have now been designed in the lab to zip together in much the same way that DNA molecules zip up to form a double helix. The technique, whose development was led by University of Washington School of Medicine scientists, could enable the design of protein nanomachines that can potentially help diagnose and treat disease, allow for the more exact engineering of cells and perform a wide variety of other tasks. The research was performed at UW Medicine's Institute of Protein Design and the Howard Hughes Medical Institute. The researchers report their findings in the December 19th, 2018 issue of the journal Nature. Learn More

Princeton molecular biologist Bonnie Bassler and graduate student Justin Silpe have identified a virus, VP882, that can listen in on bacterial conversations -- and then, in a twist, they found a way to use that to make it attack bacterial diseases like E. coli and cholera. "The idea that a virus is detecting a molecule that bacteria use for communication -- that is brand-new," said Bassler, the Squibb Professor of Molecular Biology. "Justin found this first naturally occurring case, and then he re-engineered that virus so that he can provide any sensory input he chooses, rather than the communication molecule, and then the virus kills on demand." Their paper will appear in the January 10th, 2019 issue of the journal Cell. Learn More

After over a decade of preclinical research and development, a new gene therapy treatment for sickle cell anemia (SCA) is reversing disease symptoms in two adults and showing early potential for transportability to resource-challenged parts of the world where SCA is most common. Preliminary data from a pilot Phase 1-2 clinical trial testing the gene-addition therapy were presented Dec. 3 at the American Society of Hematology's (ASH) annual meeting in San Diego by principal investigator Punam Malik, MD. She is a physician-scientist at the Cincinnati Children's Cancer and Blood Diseases Institute and director of its Comprehensive Sickle Cell Center. Malik called the data promising. Learn More

In the wild uproar around an experiment in China that claimed to have created twin girls whose genes were altered to protect them from HIV, there's something worth knowing-research to improve the next generation of humans is happening in the U.S., too. In fact, it's about to happen at Harvard University.At the school's Stem Cell Institute, IVF doctor and scientist Werner Neuhausser says he plans to begin using CRISPR, the gene-editing tool, to change the DNA code inside sperm cells. The objective: to show whether it is possible to create IVF babies with a greatly reduced risk of Alzheimer's disease later in life. To be clear, there are no embryos involved-no attempt to make a baby. Learn More

Epigenetic therapies, those targeting enzymes that alter what genes are turned on or off in a cell, are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant. Researchers at Boston Children's Hospital now report that at least one epigenetic therapy that initially looked promising for lung cancer actually has the opposite effect, boosting cancer stem cells that are believed to drive tumors. They also identify a strategy that reduces these cells, curbing lung cancer in mice. The findings were published online in Nature Communications. Learn More

Scientists at The Wistar Institute and collaborators have successfully engineered novel DNA-encoded monoclonal antibodies (DMAbs) targeting Zaire Ebolavirus that were effective in preclinical models. Study results, published online in Cell Reports, showed that DMAbs were expressed over a wide window of time and offered complete and long-term protection against lethal virus challenges. DMAbs may also provide a novel powerful platform for rapid screening of monoclonal antibodies enhancing preclinical development. Learn More

Promising findings from preclinical animal studies show the potential of gene therapy for treating incurable neurological disorders. In recently presented research scientists successfully used gene therapy to slow the progression and improve symptoms of disorders such as amyotrophic lateral sclerosis and Parkinson's disease. The findings were presented at Neuroscience 2018, the annual meeting of the Society for Neuroscience. Learn More

Biophysicists at Ruhr-Universität Bochum (RUB) have demonstrated that Raman microscopy can be used to detect the resistance of tumour cells to cancer drugs. Unlike conventional approaches, this method does not require any antibodies or markers. It detects the response of cells to administered drugs and therefore could determine the effect of drugs in preclinical studies. The team headed by Professor Klaus Gerwert and Dr. Samir El-Mashtoly from the RUB Department of Biophysics, in collaboration with Professor Stephan Hahn from the RUB Department of Molecular GI-Oncology, published an article on their work in the journal Scientific Reports on October 15th, 2018. Learn More

Biophysicists at Ruhr-Universität Bochum (RUB) have demonstrated that Raman microscopy can be used to detect the resistance of tumour cells to cancer drugs. Unlike conventional approaches, this method does not require any antibodies or markers. It detects the response of cells to administered drugs and therefore could determine the effect of drugs in preclinical studies. The team headed by Professor Klaus Gerwert and Dr. Samir El-Mashtoly from the RUB Department of Biophysics, in collaboration with Professor Stephan Hahn from the RUB Department of Molecular GI-Oncology, published an article on their work in the journal Scientific Reports on October 15th, 2018. Learn More

Scientists have reported this week that they used the genome-editing technique CRISPR to alter the DNA of laboratory mice in the womb, eliminating an often-fatal liver disease before the animals had even been born. The research, by a team at the University of Pennsylvania and the Children's Hospital of Philadelphia (CHOP), is a very early proof of concept. But while CRISPRing human fetuses is years away, at best, the success in mice bolsters what Dr. William Peranteau, who co-led the study, calls his dream of curing genetic diseases before birth. Learn More

The Nobel Assembly at Karolinska Institutet has today decided to award the 2018 Nobel Prize in Physiology or Medicine jointly to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation. Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer. Learn More

Harnessing the immune system to treat cancer shows great promise in some patients, but for many, the response does not last long-term. In an effort to find out why, Fred Hutchinson Cancer Research Center scientists are using a new technology to look at how cancer cells change under the pressure of immunotherapy treatments. In a study published on September 24th, 2018 in Nature Communications, researchers used a newly developed method for measuring molecules in single cells to deeply analyze the response to a combination immunotherapy for patients with Merkel cell carcinoma, a rare skin cancer caused by a common virus. Learn More

Human skeletal stem cells that become bone, cartilage, or stroma cells have been isolated from fetal and adult bones. This is the first time that skeletal stem cells, which had been observed in rodent models, have been identified in humans. The researchers were also able to derive the skeletal stem cells from human induced pluripotent stem cells, opening up new therapeutic possibilities. The discovery, by researchers at Stanford University, was published this week in the journal Cell. Learn More

Cancer cells often have mutations in their DNA that can give scientists clues about how the cancer started or which treatment may be most effective. Finding these mutations can be difficult, but a new method may offer more complete, comprehensive results. A team of researchers at Penn State has developed a new framework that can combine three existing methods of finding these large mutations -- or structural variants -- into a single, more complete picture. The new method, published this week in Nature Genetics,
could help researchers find new structural variations within cancer cell DNA and learn more about how those cancers begin. Learn More

"Lego block" artificial cells that can kill bacteria have been created by researchers at the University of California, Davis Department of Biomedical Engineering. The work appears in the August 29th edition of the journal ACS Applied Materials and Interfaces.The team's artificial cells mimic the essential features of live cells, but are short-lived and cannot divide to reproduce themselves. The cells were designed to respond to a unique chemical signature on E. coli bacteria. They were able to detect, attack and destroy the bacteria in laboratory experiments. Learn More

Scientists have traditionally believed that combining more than two drugs to fight harmful bacteria would yield diminishing returns. Now, a team of UCLA biologists has discovered thousands of four- and five-drug combinations of antibiotics that are more effective at killing harmful bacteria than the prevailing views suggested. Their findings, reported today in the journal npj Systems Biology and Applications, could be a major step toward protecting public health at a time when pathogens and common infections are increasingly becoming resistant to antibiotics. Learn More

A new study published in the journal Nucleic Acids Research, led by the Spanish National Cancer Research Centre (CNIO), reveals that up to 20% of genes classified as coding, those that produce the proteins that are the building blocks of all living things, may not be coding after all because they have characteristics that are typical of non-coding or pseudogenes (obsolete coding genes). The consequent reduction in the size of the human genome could have important effects in biomedicine since the number of genes that produce proteins and their identification is of vital importance for the investigation of multiple diseases. Learn More

A universal flu vaccine that protects people against most influenza strains is one step closer to reality, with a study from the Perelman School of Medicine at the University of Pennsylvania. The candidate vaccine, described in Nature Communications this week, elicited a strong antibody response to a structure on the surface of flu viruses, called the hemagglutinin (HA) stalk. It protected mice from infection by various flu strains. "This vaccine was able to do something that most other candidate flu vaccines have not been able to do," said study co-senior author Drew Weissman, MD, PhD, a professor of Infectious Diseases. "It was able to elicit protective responses against a conserved region that offers broad protection." Learn More

Scientists in China have used a next-generation form of CRISPR genome-editing to repair a disease-causing mutation in human embryos, the first use of the technique in viable embryos that were created by a standard fertility clinic technique. The study is a notable advance over previous attempts to edit human embryos and brings closer the day when genome editing might be used to alter the DNA of early-stage IVF embryos in such a way that the changes would be inherited by subsequent generations, potentially wiping out diseases caused by single genetic mutations.
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Research led by a Salk Institute scientist suggests why, at a cellular level, this might be true. The team reports that brief exposures to stressors can be beneficial by prompting the cell to trigger sustained production of antioxidants, molecules that help get rid of toxic cellular buildup related to normal metabolism. The research, which appeared in the journal Cell Metabolism this week, also revealed that short-term stress to cells leads to remodeling mitochondria, the powerhouses of the cell that deteriorate with age, so they generate fewer toxic byproducts. The findings could lead to new approaches to counter the cellular effects of aging, possibly even extending lifespan. Learn More

A new study published in Nature Communications from MIT and Massachusetts Eye and Ear has found that glaucoma may, in fact, be an autoimmune disorder. In a study of mice, the researchers showed that the body's own T cells are responsible for the progressive retinal degeneration seen in glaucoma. Furthermore, these T cells appear to be primed to attack retinal neurons as the result of previous interactions with bacteria that normally live in our body. The discovery suggests that it could be possible to develop new treatments for glaucoma by blocking this autoimmune activity, the researchers say. Learn More

In a laboratory study of endothelial cells at the University of Exeter, researchers tested compounds designed to target mitochondria. In the samples used in the study, the number of senescent cells was reduced by up to 50%. The Exeter team also identified two splicing factors that play a key role in when and how endothelial cells become senescent. The findings raise the possibility of future treatments not only for blood vessels, which become stiffer as they age, raising the risk of problems including heart attacks and strokes, but also for other cells. Learn More

Scientists at the University of Texas at Austin have found conclusive evidence that Cas9, the most popular enzyme currently used in CRISPR gene editing, is less effective and precise than one of the lesser-used CRISPR proteins, Cas12a. Because Cas9 is more likely to edit the wrong part of a plant's or animal's genome, disrupting healthy functions, the scientists make the case that switching to Cas12a would lead to safer and more effective gene editing. The study was published this week in the journal Molecular Cell. Learn More

Scientists have discovered that a well-known DNA repair pathway, the Fanconi anemia pathway, surprisingly plays a key role in repairing double-strand DNA breaks created by CRISPR-Cas9. It acts as a traffic cop to steer repair to simple end-joining or to patching the cut with new, single-strand DNA. Scientists could potentially tweak proteins involved in the pathway to preferentially steer the outcome toward replacement with DNA, which is important for gene therapy for hereditary diseases.The discovery gives insight into why CRISPR-Cas9 gene editing works remarkably well in nearly every cell attempted, though not with equal success with all cells. Learn More

The discovery of microRNAs encoded by papillomaviruses supports the important role of these small molecules in persistent infection, according to a study published July 26th in the open-access journal PLOS Pathogens. Study author Rachel Chirayil of the University of Texas at Austin and colleagues made this discovery using a new approach that enables microRNA identification for the enormous range of pathogens that have genomic data but cannot be cultured in a laboratory setting. Learn More

Research published this week in Nature suggests that CRISPR-Cas9 can cause significantly greater genetic havoc than experts thought, the study concludes, perhaps enough to threaten the health of patients who would one day receive
CRISPR-based therapy. The DNA damage found in the new study included deletions of thousands of DNA bases, this includes deletions at spots far from the edit. Some of the deletions can silence genes that should be active while activating genes that should be silent, including genes known to cause cancer. Learn More

In an achievement that has significant implications for research, medicine, and industry, UC San Francisco scientists have genetically reprogrammed the human immune cells known as T cells without using viruses to insert DNA. The researchers said they expect their technique -- a rapid, versatile, and economical approach employing CRISPR gene-editing technology -- to be widely adopted in the burgeoning field of cell therapy, accelerating the development of new and safer treatments for cancer, autoimmunity, and other diseases, including rare inherited disorders. The new method, described in the July 11, 2018 issue of Nature, relies on electroporation. Learn More

Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) and the FIRC Institute of Molecular Oncology (IFOM) in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification, this is accomplished by confining them to a defined geometric space for an extended period of time. "Our breakthrough findings will usher in a new generation of stem cell technologies for tissue engineering and regenerative medicine that may overcome the negative effects of geonomic manipulation," said Prof Shivashankar.
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The effectiveness of antibiotics can be altered by combining them with each other, non-antibiotic drugs or even with food additives. Depending on the bacterial species, some combinations stop antibiotics from working to their full potential whilst others begin to defeat antibiotic resistance, report EMBL researchers and collaborators in Nature on July 4th, 2018. In the first large-scale screening of its kind, scientists profiled almost 3000 drug combinations on three different disease-causing bacteria. The research was led by EMBL group leader Nassos Typas. Learn More

Researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences have developed an oral delivery method that could dramatically transform the way in which diabetics keep their blood sugar levels in check. By encapsulating the insulin-ionic liquid formulation in an enteric coating, the team overcame the challenge of resisting a breakdown by gastric acids in the gut. This polymer coating dissolves when it reaches a more alkaline environment in the small intestine, where the ionic liquid carrying insulin is released. The research was published in the Proceedings of the National Academy of Sciences. Learn More

Cancer researchers at KU Leuven in Belgium have shown that some patients with T-cell leukemia produce too much of the BCL-2 protein. The overproduction of the BCL-2 protein is due to a defect in the ribosome, the protein factory of the cell. This defect is found in 10% of the pediatric patients with T-cell leukemia. Cancer cells take advantage of this 'survival protein' which allows them to escape chemotherapy. The impact of this ribosome defect on T-cell leukemia has never been elucidated before. A drug suppressing this BCL-2 shows promising results. Learn More

Researchers at Columbia University Irving Medical Center (CUIMC) have developed a highly innovative computational framework that can support personalized cancer treatment by matching individual tumors with the drugs or drug combinations that are most likely to kill them. The study, published this week on Nature Genetics, by Dr. Andrea Califano of Columbia University Irving Medical Center and Dr. Irvin Modlin of Yale University and Wren Laboratories LLC, co-senior author on the study, with collaborators from 17 research centers worldwide, details a proof of concept for a novel analytical platform applicable to any cancer type.
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To fight cancer, researchers increasingly use vaccines that stimulate the immune system to identify and destroy tumor cells. However, the desired immune response is is not always guaranteed. In order to strengthen the efficacy of vaccines on the immune system -- and in particular on T lymphocytes, specialized in the detection of cancer cells -- researchers from the universities of Geneva (UNIGE), Freiburg (UNIFR), Munich, and Bayreuth, in collaboration with the German company AMSilk, have developed spider silk microcapsules capable of delivering the vaccine directly to the heart of immune cells. This process, published in the journal Biomaterials, could also be applied to preventive vaccines... Learn More

Researchers at the University of Pennsylvania's Abramson Cancer Center say a patient treated for chronic lymphocytic leukemia (CLL) in 2013 went into remission because of a single CAR T cell and the cells it produced as it multiplied, and has stayed cancer free in the five years since, with CAR T cells still present in his immune system. The findings, published this week in Nature, show the response is tied to where the CAR gene inserted itself into the patient's T cell DNA, a key factor that may help improve response rates to the therapy. Learn More

A new discovery about the effects of aging in our cells could allow doctors to cure or prevent diabetes, fatty liver disease and other metabolic diseases -- and possibly even turn back the clock on aging itself. The new discovery from the lab of Irina M. Bochkis, PhD, of UVA's Department of Pharmacology, shows that the location of our DNA inside the cell's nucleus is critically important. Genes that are turned off are shoved up against the nuclear membrane, which encases the nucleus. But with age, our nuclear membranes become lumpy and irregular, and that prevents genes from turning off appropriately. Learn More

Scientists know that faulty proteins can cause harmful deposits or "aggregates" in neurological disorders such as Alzheimer's and Parkinson's disease. Although the causes of these protein deposits remain a mystery, it is known that abnormal aggregates can result when cells fail to transmit proper genetic information to proteins. University of California San Diego Professor Susan Ackerman and her colleagues first highlighted this cause of brain disease more than 10 years ago. Now, probing deeper into this research, she and colleagues have identified a gene, Ankrd16, that prevents the protein aggregates they originally observed.
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Biochemists have determined the detailed structure of a volume-regulated chloride channel. This cellular valve is activated in response to swelling to prevent the cell from bursting. The protein also plays an important role in the uptake of chemotherapeutics and the release of neurotransmitters after a stroke. The controlled regulation of its activity thus opens up a promising strategy for novel therapies. The study findings are published in this months issue of the journal Nature. Learn More

A new study published in Science by Professors Yossi Paltiel of the Hebrew University of Jerusalem and Ron Naaman from the Weizmann Institute of Science describes a breakthrough technology with the power to create drugs with fewer unwanted side effects. Chemical compounds are made up of molecules. The most important molecules in biology are chiral molecules. "Chiral," the Greek word for "hand," describes molecules that look almost exactly alike and contain the same number of atoms but are mirror images of one another -- meaning some are "left-handed" and others are "right-handed." This different "handedness" is crucial and yields different biological effects. Now, following a decade of collaborative research, Paltiel and Naaman have discovered a uniform, generic method that will enable pharmaceutical and chemical manufacturers to easily and cheaply separate right from left chiral molecules. Learn More

In work that will help make the gene-editing process more precise, researchers at the Joint Institute of Metrology and Biology (JIMB, a collaboration between Stanford University and the National Institute of Standards and Technology, or NIST), have developed a new kind of CRISPR platform called MAGESTIC. Taking its name from the phrase "multiplexed accurate genome editing with short, trackable, integrated cellular barcodes," the new platform makes CRISPR less like a blunt cutting tool and more like a word processor by enabling an efficient "search and replace" function for genetic material. Announced in a Nature Biotechnology paper, MAGESTIC also produced a sevenfold increase in cell survival during the editing process. Learn More

A Northwestern-led synthetic biology research team has combined technologies to develop a new biotech technique that promises to accelerate research into protein therapies that could one day become the next defense against antibiotic-resistant supergerms or the next new drug. The resulting advance is described in "Design of glycosylation sites by rapid synthesis and analysis of glycosyl-transferases," published this week by the journal Nature Chemical Biology. The new technique promises to vastly speed up the time needed to test compounds for potential new drugs. As recent as a few decades ago, drugs were based on natural products that were tediously isolated and characterized from plants and other natural sources. Learn More

As people age, their intestinal stem cells begin to lose their ability to regenerate. These stem cells are the source for all new intestinal cells, so this decline can make it more difficult to recover from gastrointestinal infections or other conditions that affect the intestine. This age-related loss of stem cell function can be reversed by a 24-hour fast, according to a new study from MIT biologists. The researchers found that fasting dramatically improves stem cells' ability to regenerate, in both aged and young mice. In fasting mice, cells begin breaking down fatty acids instead of glucose, a change that stimulates the stem cells to become more regenerative. The researchers found that they could also boost regeneration with a molecule that activates the same metabolic switch. Such an intervention could potentially help older people recovering from GI infections or cancer patients undergoing chemotherapy, the researchers say. Learn More

The breast cancer drug lapatinib which is designed to shrink tumors can sometimes cause them to grow in the lab, according to a new study published in eLife. By understanding the molecular basis of this phenomenon, scientists hope that their findings will lead to safer treatment decision-making and drug design in the future. Lapatinib is used in combination with other cancer drugs and chemotherapy to treat patients with a particular type of advanced breast cancer, but failed clinical trials as a stand-alone treatment. Researchers at the Francis Crick Institute, King's College London and Barts Cancer Institute, Queen Mary University of London, have shown that lapatinib itself can actually cause breast cancer cells to grow more rapidly in some situations, which might explain the disappointing outcome of the clinical trials. Learn More

Previous scientific wisdom has discredited combining virotherapy and externally added NK cell therapy to the body's natural killer (NK) cells, but there could be clear cancer-fighting benefits -- providing enough external NK cells are deployed to destroy the tumor and stop its spread, as revealed in the paper published this week in Proceedings of the National Academy of Sciences. To reach this conclusion, physicians devised a mathematical formula unlocking the complex interactive relationship between externally introduced viruses and NK cells in addition to the immune system's existing NK cells to calculate cancer cell-killing potency. The mathematical modeling was able to predict how a virus-treated tumor would respond to NK cell therapy, depending on the number of NK cells introduced to the tumor. Learn More

More than 30 years ago, when UC Berkeley researchers discovered telomerase, an enzyme that lengthens chromosome ends and prevents them from fraying enough to kill a cell, speculation ran wild about its role in aging and cancer, setting off a full-court press to produce drugs to activate or block the enzyme. While neither telomerase-based anti-aging drugs, touted as a "fountain of youth," nor anticancer drugs have yet appeared, the publication today in the journal Nature by UC Berkeley scientists of the first detailed picture of the molecular structure of human telomerase should jump-start that effort, allowing more targeted drug screens and intelligent design of new drugs.
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Using a homemade, high-tech microscope, scientists at the University of Virginia School of Medicine have revealed how a cancer-causing virus anchors itself to our DNA. That discovery could pave the way for doctors to cure incurable diseases by flushing out viruses, including HPV and Epstein-Barr, that now permanently embed themselves in our cells. The researchers used the microscope built by fellow investigator M. Mitchell Smith, PhD, to reveal the structure of the tether used by a virus called Kaposi's sarcoma-associated herpesvirus (KSHV). Until now, such tethers have largely eluded scientists because they are so diabolically small, defying even the most high-tech approaches to determining their form. Learn More

The 'bad apples' of the immune system are also its secret weapon, according to major Australian research published today in the world-leading journal Science.In a world first, scientists from Sydney's Garvan Institute of Medical Research have revealed how a population of 'bad' antibodies in the immune system, which are usually 'silenced' because they can harm the body, can provide crucial protection against invading microbes. The new findings show for the first time that 'bad' antibodies go through a rapid 'redemption' process and are activated when the body is faced with a disease threat that other antibodies cannot tackle. Learn More

Health departments working with CDC's Antibiotic Resistance (AR) Lab Network found more than 220 instances of germs with "unusual" antibiotic resistance genes in the United States last year, according to a CDC Vital Signs report released this week. Germs with unusual resistance include those that cannot be killed by all or most antibiotics, are uncommon in a geographic area or the U.S., or have specific genes that allow them to spread their resistance to other germs. Rapid identification of the new or rare threats is the critical first step in CDC's containment strategy to stop the spread of antibiotic resistance (AR). Learn More