Publisher Health

A team co-led by scientists at Scripps Research has used advanced imaging methods to reveal how the production of the Alzheimer’s-associated protein amyloid beta (Aβ) in the brain is tightly regulated by cholesterol.
Appearing on line Thursday ahead of print in the Aug. 17 issue of the Proceedings of the National Academy of Sciences (PNAS), the scientists’ work advances understanding of how Alzheimer’s disease develops and underscores the long-underappreciated role of brain cholesterol. The findings also help explain why genetic studies link Alzheimer’s risk to a cholesterol-transporting protein called apolipoprotein E (apoE).
“We showed that cholesterol is acting essentially as a signal in neurons that determines how much Aβ gets made — and thus it should be unsurprising that apoE, which carries the cholesterol to neurons, influences Alzheimer’s risk,” says study co-senior author Scott Hansen, PhD, an associate professor in the Department of Molecular Medicine at Scripps Research, Florida.
The other co-senior author of the study was Heather Ferris, MD, PhD, assistant professor in the Department of Medicine at the University of Virginia School of Medicine. The study’s first author, Hao Wang, is a graduate student in the Hansen lab.
Understanding Aβ
A type of Aβ in the Alzheimer’s brain can form large, insoluble aggregates that gather in extensive clumps or “plaques” — one of the most prominent features of the disease at autopsy. Genetic evidence correlates the production of a subtype of Aβ with Alzheimer’s, yet Aβ’s role in both the healthy brain and in disease remain a subject of debate, after many clinical trials of Aβ-clearing therapeutics have struggled to show a benefit.

Some proteins in cells can separate into small droplets like oil droplets in water, but faults in this process may underlie neurodegenerative diseases in the brains of older people. Now, Rutgers researchers have developed a new method to quantify protein droplets involved in these diseases.
The novel technique, which simultaneously quantifies the surface tension and viscosity, or thickness, of protein droplets, will help scientists to study how they change, opening the way to improved understanding of the mechanisms of these diseases and the development of drug treatments.
The study appears in the journal Biophysical Reports.
The Rutgers-led team studied biomolecular condensates, which are liquid droplets that arise through the liquid-liquid phase separation of proteins and RNA inside cells in a process similar to how oil forms droplets in water.
The material properties of these protein droplets are important because they play pivotal roles in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s and Parkinson’s diseases. The basic idea is that liquid droplets of certain proteins can change to clogs, or aggregates of molecules, which are hallmarks of these diseases.
Surprisingly, there are no well-established methods to quantify the material properties of these protein droplets, mainly because they are very small — about a trillionth of the volume of a rain drop. The researchers developed a straightforward method, taking inspiration from how you drink through a straw: the suction pressure in your mouth and the speed that the beverage flows in the straw can tell you the property of the liquid beverage. Similarly, one can measure the material properties of protein droplets by looking at how a droplet moves in and out of the tip of a tiny glass tube called micropipette.
The researchers looked at droplets of common liquids such as oil and water. It turns out that extreme pressure is needed to move them into a micropipette in order to overcome the high surface tension of these liquids in such a narrow passage. But once that tension is overcome, oil and water droplets move too quickly to be captured on camera because of their low viscosity. The researchers found, however, that protein droplets have just the right surface tension and viscosity to be studied quantitatively using a micropipette.
“The fact that we can apply the micropipette technique to accurately measure biomolecular condensates highlights a major difference between protein droplets and common liquids: the surface tension of protein droplets are thousands of times lower, while their viscosity are thousands of times higher than those of oil or water,” said senior author Zheng Shi, an assistant professor in the Department of Chemistry and Chemical Biology at Rutgers-New Brunswick.
“We can now finally study in a quantitative manner how material properties of protein droplets change during neurodegeneration. We anticipate this technique will be widely applicable and resolve several limitations regarding current approaches. It will open doors for unravelling the mechanisms as well as facilitating therapeutic advances in the treatment of these diseases.”
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Materials provided by Rutgers University. Original written by John Cramer. Note: Content may be edited for style and length.

A new study led by University of California, Irvine (UCI) researchers identifies two ways in which APOBEC3A — a vital enzyme that is responsible for genetic changes resulting in a variety of cancers while protecting our cells against viral infection — is controlled.
The enzyme APOBEC3A is a vital part of the innate immune system that works to protect cells from viral infection by inducing mutations to block viruses from replicating. However, APOBEC3A also induces mutations by directly attacking the genome of cancer cells, which results in increased levels of DNA mutations that lead to cancer progression, metastasis and drug resistance.
“In our previous studies, we demonstrated that APOBEC3A-induced DNA mutations are very frequent in cancer patients. In fact, we found they are present in up to 80 percent of certain cancer types such as lung, breast or bladder cancers,” said Rémi Buisson, PhD, assistant professor in the UCI School of Medicine Department of Biological Chemistry.
Titled, “Genotoxic Stress and Viral Infection Induce Transient Expression of APOBEC3A and Pro-Inflammatory Genes Through Two Distinct Pathways,” the study was published today in Nature Communications.
In this study, graduate student Sunwoo Oh and Elodie Bournique, PhD, a postdoctoral fellow, both at UCI School of Medicine, characterized how both viral infection and genotoxic stress caused by chemotherapeutic drugs transiently up-regulate APOBEC3A. Their work illustrates how viral infection triggers a specific innate immune response to activate APOBEC3A expression in human cells and how it is an important step in the elimination of the virus. Their work also illustrates how different chemotherapeutic drugs stimulate APOBEC3A, but through a completely different type of immune response which, this time, causes mutations that further enhance cancer aggressivity.
“Together, our results reveal different ways for the cells to regulate APOBEC3A expression to address different types of stresses that the cell may encounter,” said Buisson. “By understanding how cancer cells and viral infections regulate APOBEC3A expression, we are poised to take critical step forward toward the development of both new therapeutic strategies to fight cancer and new anti-viral therapies.”
More work is needed to develop strategies to prevent the formation of DNA mutations caused by APOBEC3A in the cancer genome that increase tumor heterogeneity, promoting disease progression and resistance to therapies. With regard to viral infections, the next step is to determine whether certain types of mutations previously detected in viruses such as SARS-CoV-2 (COVID-19) are the result of APOBEC3A activity and affect the replication of the virus in the cells.
This study was funded in part by the National Institutes of Health, California Breast Cancer Research Program, Concern Foundation, National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Public Health Service.
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A new study exposes the dire need for new clinical risk management tools to help hospital healthcare workers prevent the deaths and intensive care admissions of Black, Asian and minority ethnic (BAME) COVID-19 patients with pneumonia, say researchers.
The call for healthcare policy change comes after a new study led by the University of Birmingham has revealed ethnic minority COVID-19 patients from areas with the highest levels of household overcrowding, air pollution, poor housing quality and adult skills deprivation are more likely to be admitted to hospital suffering pneumonia and requiring intensive care. Indian, Pakistani, African, Caribbean, Chinese, Bangladeshi and mixed ethnicity patients were all more likely than Caucasians to be admitted from an area with at least one form of deprivation.
The first of its kind study of 3,671 patients with COVID-19 admitted to four Midland hospitals provides new important and detailed insights into the stark contrasts between ethnic minorities and Caucasians.
It found 81.5% of ethnic minority COVID-19 patients were more likely to be admitted to hospital from regions of highest air pollution deprivation compared with 46.9% of Caucasians. 81.7% of hospitalised ethnic minority COVID-19 patients were more likely to be admitted from regions of highest household overcrowding deprivation compared with 50.2% of Caucasians.
Crucially, the study found that existing tools used by medics to predict or measure risk and manage the care of COVID-19 patients with pneumonia are insufficient, and can result in underscoring of ethnic minority patients. This is particularly due to the fact that often they do not take into consideration that ethnic minority patients are at greater risk of serious illness with COVID-19 at a younger age than Caucasians. The study found of those patients hospitalised, ethnic minorities , including Indian, Pakistani, African, Chinese, Bangladeshi and any other non-Caucasian ethnic group were under the age of 65, while Caucasians were older than 65.
Existing scoring also does not take into account important risk factors that ethnic minority patients are much more exposed or vulnerable to, including suffering multiple pre-existing underlying health conditions, obesity, and deprivation, such as living in overcrowded households or areas of high pollution.
The researchers say underscoring can potentially lead to inappropriate levels of care as clinicians are left falsely reassured regarding the severity of illness and risk of a patient’s deterioration.
The results showed ethnic minority patients with pneumonia and low CURB65 scores — a tool used by clinicians to predict severity of pneumonia — had higher mortality than Caucasians (22.6% vs 9.4% respectively). Africans were at highest risk (38.5%), followed by Caribbean (26.7%), Indian (23.1%), and Pakistani (21.2%) patients.
The research was supported by the National Institute for Health Research (NIHR) and its publication comes following the gripping BBC 1 documentary “Why is COVID killing people of colour?” which was released earlier this year where the lead author, Dr Marina Soltan, was interviewed by David Harewood following a previous study she led showing that patients with chronic conditions such as hypertension or kidney disease are nearly twice as likely to die from COVID-19 and that many patients with these conditions come from deprived areas.
Lead author Dr Marina Soltan, a NIHR Academic Clinical Fellow in Respiratory Medicine at the University of Birmingham and the NHS England Health Inequalities Improvement Policy and Delivery Lead for Data and Research, said: “The COVID-19 pandemic has shone a harsh light on health inequalities. This study demonstrates an urgent need for the development of novel clinical risk stratification tools, ensuring they reflect risk factors to which ethnic minorities are predominantly predisposed.”
“This work has implications for how we train healthcare professionals to recognise multi-ethnic risk factors and public health implications for how to narrow the gap on health inequalities.
“Meanwhile, partnership with both government and industry is beneficial to prevent the rise in the number of patients with multiple chronic illnesses and reduce inequalities, ensuring everyone has access to suitable housing, employment and education opportunities, regardless.”

The interrupted non-coding regions in pre-mRNAs, termed “introns,” are excised by “splicing” to generate mature coding mRNAs that are translated into proteins. As human pre-mRNA introns vary in length, the splicing mechanisms and factors involved are likely not universal. A study by researchers from Fujita Health University in Japan reports a subset of human short introns that are spliced by novel essential splicing factor, SPF45 (RBM17), instead of by a known splicing factor, U2AF dimer.
Protein-coding genes carry the blueprint for protein production. In higher organisms, however, most of the coding-gene transcripts, or pre-mRNAs, are separated by non-coding sequences called “introns,” which must be cut out or “spliced” to make mature mRNA that can be translated into protein.
Human pre-mRNA introns vary extensively in their lengths, ranging from under fifty to over a million nucleotides (nt). Human pre-mRNA splicing involves dynamic stepwise reactions in a huge protein-RNA complex called “spliceosome,” which includes five kinds of small nuclear ribonucleoproteins, called U snRNPs, and many protein factors. The essential splicing signal sequences in pre-mRNA — the 5′ splice site, the branch-site sequence, and the poly-pyrimidine tract (PPT) followed by the 3′ splice site — are bound by the splicing factors U1 snRNP, U2 snRNP, and U2AF65/U2AF35, respectively, which together constitute the spliceosomal A complex. The globular shape of the A complex fully occupies the length of a 79-125 nt single-stranded RNA, which is about two-fold longer than the known short introns (43-56 nt). How are these short introns able to accommodate the oversized complex with the known essential factors? It may be assumed that such short introns are spliced out by alternate mechanisms.
Now, a team of researchers led by Professor Akila Mayeda from the Institute for Comprehensive Medical Science, Fujita Health University, Japan, has attempted to answer this question in their latest study published in Nature Communications. Elaborating their findings, the paper’s co-author Kazuhiro Fukumura says, “The length variation of human pre-mRNA introns is extensive, ranging from fifty to over a million nucleotides. We thus postulate that there is possibly a distinct alternate splicing mechanism involved in splicing of human short introns.”
The team began by searching for essential factors to splice out human short introns from 154 human nuclear proteins. They downregulated these proteins’ expression in a human cell line (HeLa cells) using small interfering RNAs (siRNA). To analyze splicing activity, they selected HNRNPH1 pre-mRNA (heterogeneous nuclear ribonucleoprotein H1) including a 56-nt short intron.
The strongest splicing repression in HNRNPH1 pre-mRNA with 56-nt intron was caused by knockdown of SPF45, but no splicing repression was observed in pre-mRNA with control 366-nt intron. To further confirm that SPF45 is a common splicing factor for a group of short introns, they performed whole-transcriptome sequencing with RNA prepared from the SPF45-knockdown cells. The most frequent changes of splicing in SPF45-knockdown cells were intron retention, and 187 of the retained introns were identified. Remarkably, the length distribution of these SPF45-dependent introns was strongly biased towards shorter lengths. This suggested that SPF45 is required for the splicing of many pre-mRNAs with short introns.
Next, the researchers investigated the factor that determined the SPF45-dependence of some short introns. A PPT sequence and the downstream 3′ splice site is required for binding of the known authentic splicing factor U2AF heterodimer (U2AF65/U2AF35). Notably, a truncation in this PPT led to SPF45-dependency, suggesting that short PPT is crucial for SPF45-dependent splicing. As expected, a knockdown of the U2AF heterodimer significantly decreased the splicing of conventional introns; SPF45-dependent short introns, however, were spliced out rather efficiently, suggesting that SPF45 expels U2AF heterodimer on truncated PPTs and the newly installed SPF45 promotes short intron splicing. Finally, biochemical analyses and splicing assays with various mutant SPF45 proteins helped establish the model of SPF45-dependent splicing on a short intron with a truncated PPT.
Previously, SPF45 was reported to function as a regulator of alternative splicing; however, SPF45 is also an essential factor for cell survival and maintenance in vivo. The research team offers a solution to this enigma by demonstrating that SPF45 is a novel and distinct constitutive splicing factor in the early spliceosome, i.e., a subset of human short introns with truncated PPTs is spliced out with SPF45 but not with previously known authentic U2AF heterodimer.
Prof. Mayeda states, “This is a ground-breaking accomplishment in terms of basic research; however, the applications of our findings are also potentially intriguing.Overexpression of SPF45 confers multidrug resistance to anticancer drugs. Presumably, the genes involved in this mechanism harbor SPF45-dependent introns. Thus, overexpression of SPF45 may cause up-regulation of such genes though splicing activation of the transcripts. Understanding these mechanisms can aid in development of effective therapeutic interventions.”

The initials BRCA2 may be best known for a gene associated with many cases of breast cancer, and the protein encoded by the BRCA2 gene is critical to repairing breaks in DNA.
The breakdown of this interaction is a hallmark of many cancers. Now, U-M scientists have determined the structure of a complex of two proteins — BRCA2 together with MEILB2 — that allows repairs to happen efficiently in cells undergoing cell-splitting, called meiosis. Their results, reported in Nature Structural and Molecular Biology, have major implications for cancer and infertility.
“We know how the literature is rich with examples of BRCA2 mutations in cancer, but our findings now suggest that the MEILB2-binding region of BRCA2 might be a hotspot for discovering mutations related to infertility,” said study author and U-M structural biologist Jayakrishnan Nandakumar, associate professor of molecular, cellular, and developmental biology.
In germ cells — the cells that give rise to sperm or eggs — DNA breaks occur in every chromosome before the cells undergo meiosis. The breaks ensure mixing of genes to create genetic diversity rather than exact copies of the parents. In meiosis, each germ cell splits twice so that each egg or sperm ends up with only one copy of each chromosome. Then when egg meets sperm, the embryo has the right number of chromosome pairs.
Before the first split occurs, the chromosomes in the germ cell pair up tightly and then each chromosome within a pair breaks and rejoins with pieces from its partner to exchange genes in a process called crossover. Then all these DNA breaks need to be rejoined quickly.
Think of a sandwich, Nandakumar explains. The “bun” is composed of four identical copies of a protein called MEILB2 on the top and bottom, with the two BRCA2 proteins between. The MEILB2 protein sandwich carries the BRCA2 protein precisely to the DNA break points.

Despite tremendous advances in medicine, tumors are challenging to cure because they are made up of heterogeneous cells. Like human families, the individual cells of a tumor share some common traits and characteristics, but as the tumor expands, the cells also develop their own identities. And, as a result, some cells are more resistant to therapy than others and quicker to adapt and change.
A team of researchers at The University of Texas at Austin developed a new way to tag tumor cells to figure out how they evolve and change over time to resist cancer treatments. They studied chronic lymphocytic leukemia (CLL) primarily, but these findings could help researchers learn more about the entire spectrum of cancerous tumors.
“This is a technology that lets you replay the evolutionary history of the tumor,” said Amy Brock, an associate professor in the Cockrell School’s Department of Biomedical Engineering and co-lead author on a new paper published in Nature Cancer. “We can collect those pre-resistant cells and go back and look at what happened to them. We can try many parallel treatments and measure how specific cells respond and which ones persist.”
The ability to essentially “tag” nucleic acids — the genetic information of the cell such as RNA or DNA — to monitor them is not a brand-new technology. However, current capabilities don’t paint a full picture of how tumor cells evolve. What this platform, known as ClonMapper, can do that wasn’t possible before is look backward and trace how tumor cells change over time. That gives researchers the ability to look at which cells “win out” over less resistant cells, continue to clone themselves and make the tumor more dangerous. By isolating these cells, researchers can better test which treatments do and don’t work against them.
Monitoring changes over time is key to successful transfer treatments. Tumor cells adjust to treatments and become resistant. That’s why patients can go into remission, but later experience relapse.
“This is one of reasons cancer treatment is so challenging — we don’t have very good ways of predicting ahead of time which cells will be sensitive to a type of drug and which ones will be resistant,” Brock said. “This acquired resistance is a leading cause of treatment failure for many patients with cancer.”
CLL is a low-grade B-cell malignancy that is often monitored for months or even years before it requires active treatment. This “watch and wait” style of treatment relies heavily on accurate monitoring of the patient. In the study, ClonMapper focused on identifying which cells were cloning themselves, how fast this process happened and how it influences the growth rate of surrounding cells over time. This allowed a much more accurate analysis of the cell population and may enable more customized treatment plans for patients.
The ClonMapper study was led by researchers from UT Austin and the Dana-Farber Cancer Institute, Harvard Medical School and the Broad Institute. The UT Austin team includes from the Cockrell School and College of Natural Sciences Aziz M. Al’Khafaji, Eric Brenner, Kaitlyn E. Johnson and Russell E. Durrett.
The UT Austin team is now deploying ClonMapper to study several different cancer types. Brock’s lab recently received funding from the National Cancer Institute to study breast cancer and has an ongoing collaboration with Dell Medical School working on colorectal carcinoma treatments.
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New biomarkers found in the eyes could unlock the key to helping manage diabetic retinopathy, and perhaps even diabetes, according to new research conducted at the Indiana University School of Optometry.
During its early stages, diabetes can affect the eyes before the changes are detectable with a regular clinical examination. However, new retinal research has found that these changes can be measured earlier than previously thought with specialized optical techniques and computer analysis.
The ability to detect biomarkers for this sight-threatening condition may lead to the early identification of people at risk for diabetes or visual impairment, as well as improve physicians’ ability to manage these patients. The study appears in the journal PLOS One.
“Early detection of retinal damage from diabetes is possible to obtain with painless methods and might help identify undiagnosed patients early enough to diminish the consequences of uncontrolled diabetes,” said study co-author Ann E. Elsner, a Distinguished Professor at the IU School of Optometry.
Diabetic retinopathy, which is caused by changes in the blood vessels in the retina, is the most common diabetic eye disease and a leading cause of blindness in U.S. adults. From 2010 to 2050, the number of Americans with diabetic retinopathy is expected to nearly double, from 7.7 million to 14.6 million.
The new study is part of the current widespread emphasis on detection of diabetic retinopathy through artificial intelligence applied to retinal images. However, some of these algorithms provide detection based on features that occur much later than the changes found in this study.
The IU-led method advances earlier detection because of the retinal image processing algorithms described in the study.
“Many algorithms use any image information that differs between diabetic patients and controls, which can identify which individuals might have diabetes, but these can be nonspecific,” Elsner said. “Our method can be combined with the other AI methods to provide early information localized to specific retinal layers or types of tissues, which allows inclusion of information not analyzed in the other algorithms.”
Elsner conducted the retinal image analysis in her lab at the IU School of Optometry’s Borish Center for Ophthalmic Research, along with her co-author, Joel A. Papay, a Ph.D. student in the Vision Science Program at the school. They used data collected from volunteers with diabetes, along with healthy control subjects. Additional data were also collected from a diabetic retinopathy screening of members of the underserved community at the University of California, Berkeley, and Alameda Health.
The computer analysis was performed on retinal image data commonly collected in well-equipped clinics, but much of the information used in this study is often ignored for diagnosis or management of patients.
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The precise transmission of genetic information from one generation to the next is fundamental to life.
Most of the time, this process unfolds with remarkable accuracy, but when it goes awry, mutations can arise — some of them beneficial, some of them inconsequential, and some of them causing malfunction and disease.
Yet, precisely where and how heritable genetic mutations tend to arise in humans has remained largely unknown.
Now, a new multi-institutional study led by investigators at Harvard Medical School and Brigham and Women’s Hospital has pinpointed nine processes during which most human genetic mutations tend to arise.
The work, published Aug. 12 in Science, is based on an analysis of 400 million rare DNA human variants and represents one of the most comprehensive computational efforts to explore heritable genomic variations.
“Genetic mutations are a rare yet inevitable and, indeed essential, part of the development and propagation of the human species — they create genetic diversity, fuel evolution, and occasionally cause genetic diseases,” said study lead investigator Shamil Sunyaev, professor of biomedical informatics in the Blavatnik Institute at HMS and professor of medicine at Brigham and Women’s.
“Harnessing the power of computation and big data, we analyzed genomic variations and identified a set of biologic processes responsible for the vast majority of heritable human mutations,” added Sunyaev, who conducted the work with lead authors Vladimir Seplyarskiy, HMS research fellow in medicine at Brigham and Women’s, and Ruslan Soldatov, instructor in biomedical informatics at HMS.
Key findings
The research identified new mutation-fueling mechanisms and some that were already known. One mechanism was related to inaccurate copying of DNA, another was related to chemical damage occurring to the DNA. The analysis also pinpointed a machinery involved in human gene regulation as a frequent culprit in mutations. This machinery is particularly active during early embryonic development, and most of the mutations introduced by the machinery occur during this period. In one surprising finding, the researchers identified a mutation-driving mechanism that was not related to DNA copying and cellular division — processes that are prone to mutation-causing glitches. This previously unsuspected mechanism leads to mutations in egg cells stored in the ovaries.
Relevance and implications
The researchers are now working to incorporate some of the results in a model of human-mutation rate along the genome in an effort to help predict the chance that a specific mutation would occur at a specific location in the genome. The goal is to help in the analysis of disease mutations and in discovery of genes causing rare diseases. The model may also serve to highlight genes of key importance to human health and survival.
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Although the world is focused on the COVID-19 pandemic, there are many other dangerous pathogens still out there, like Yersinia pestis, which causes plague — the deadly disease that killed tens of millions of people during the infamous Black Death in the 14th century. Although plague has been largely eradicated in the developed world, it still affects hundreds of people globally each year.
When a human is infected with bubonic plague from a flea bite and it goes untreated, the infection can progress and spread to the lungs, resulting in pneumonic plague. The most feared clinical form of plague, pneumonic plague is typically lethal if not quickly treated, and infected patients can transmit the disease to others via respiratory droplets. A team of scientists from Northern Arizona University’s Pathogen and Microbiome Institute, led by professor Dave Wagner, recently published their findings from a remarkable study involving antimicrobial resistant (AMR) plague.
Although pneumonic plague outbreaks are now extremely rare, scientists consider plague to be a reemerging and neglected disease, particularly in the East African island country of Madagascar, which reports the majority of annual global cases. With no vaccine against it, preventing mortality from plague requires rapid diagnosis followed by treatment with antibiotics. An AMR strain of Y. pestis — resistant to the antibiotic streptomycin, usually the first-line treatment for plague in Madagascar — was isolated from a pneumonic plague outbreak that occurred there in 2013, involving 22 cases, including three fatalities.
Wagner’s team, including PMI senior research scientists Dawn Birdsell and Nawarat Somprasong, PMI assistant director Amy Vogler, professor Herbert Schweizer, associate professor Jason Sahl and senior research coordinator Carina Hall, conducted a study of this outbreak, together with long-term research partners at the Institut Pasteur de Madagascar and scientists at the Institute Pasteur Paris and the Madagascar Ministry of Public Health. The results of the study, “Transmission of antimicrobial resistant Yersinia pestis during a pneumonic plague outbreak,” were recently published in the journal Clinical Infectious Diseases.
“By characterizing the outbreak using epidemiology, clinical diagnostics and DNA-fingerprinting approaches,” Wagner said, “we determined — for the first time — that AMR strains of Y. pestis can be transmitted person-to-person. The AMR strain from this outbreak is resistant to streptomycin due to a spontaneous point mutation, but is still susceptible to many other antibiotics, including co-trimoxazole. Luckily, the 19 cases that were treated all received co-trimoxazole in addition to streptomycin, and all of them survived.”
“The point mutation, which also is the source of streptomycin resistance in other bacterial species, has occurred independently in Y. pestis at least three times and appears to have no negative effect on the AMR strain, suggesting that it could potentially persist in nature via the natural rodent-flea transmission cycle. However, AMR Y. pestis strains are exceedingly rare and the mutation has not been observed again in Madagascar since this outbreak,” he said.
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