Tuesday, 17 July 2018

How to Conserve Energy in Pharmaceutical Manufacturing

Pharmaceutical Manufacturing
Energy conservation saves money in all industries, especially in pharmaceutical manufacturing. In an industry where temperature control is important, pharmaceutical manufacturing has unique needs and means of saving energy. Saving energy will lower costs and make you more competitive in the field.

A guest post by Megan Ray Nichols

Examine Transportation Energy

Energy use in transportation is higher than for other industries. Unlike shipping metal, pharmaceuticals require refrigerated transport units. How often the doors open on these vehicles affect the internal temperature and can cause the cooling system to run more often. Consider shipping only full vehicles at a time that go directly to their final destinations. This reduces the number of times the doors open, and a full truck, like a full freezer, keeps cold more efficiently.

The fuel used by your transport is also an important way to conserve energy. According to the Department of Energy, fuel costs for the pharmaceutical industry were over $200 million a year in 2002, and this number is likely higher today as it was on an upward trajectory from 1987 to the early 2000s. Alternative fuel sources and more fuel-efficient vehicles can cut these costs.
Rethink HVAC Systems

The HVAC system, including ventilation, accounts for 65 percent of the energy used by a pharmaceutical manufacturing facility. Consider other ways of cooling your facility. For instance, ice-based storage is used as an alternative to standard refrigeration at several pharmaceutical facilities. Electric bills for a pair of GAR Laboratories buildings dropped from $571 to $117 a month with ice-based storage. Water freezes during the cool of the night, and the chill cools off the building during the day. This is one way to cut your HVAC costs and conserve energy.
Consider Changing Cooling Systems

Walk-in coolers are considered separate from the HVAC system. You may want to think about replacing your existing coolers with something more energy efficient and requiring less maintenance. Once used only in restaurants, glycol chillers are becoming more popular in other applications such as the pharmaceutical industry.

Compared to older chiller models, glycol chillers have fewer parts, which means they are less likely to break down. A portable glycol chiller offers more flexibility and is more energy efficient than older models. These can be customized to your plant's needs.

Traditional cooling towers can use up to 1.5 million gallons of water annually. Rather than wasting so much water, consider a closed-loop system. With these systems, cooling water use drops by 98 percent. This system also never disposes of used water into the ground, where it could potentially contaminate groundwater. It also more effectively maintains the water's temperature.
Change to More Efficient Pumping Equipment

In pharmaceutical manufacturing plants in the United States, pumping accounts for a quarter of the energy used, and switching to more efficient equipment could reduce energy by 20 percent. Over the lifetime of the pump, the energy costs will add up to 95 percent of the ownership cost, compared to 2.5 percent for the purchase price and the same amount for maintenance. This means selecting the most energy-efficient pumping equipment available, even if it's more expensive, will pay off over the life of the pump.


Practice Good Energy Conservation Techniques

Changing the equipment in your facility is only part of the puzzle. You need to train your employees to adopt energy-saving habits. Teach them to turn off vent hoods and lights when not needed. You can automate these, too, with motion detecting lights and heating and cooling systems.

Increase the air conditioner temperature in the summer and lower the heat in the winter. Make even larger changes in these settings when the facility is unoccupied. Merck used this strategy at its Rahway, New Jersey plant. There, it cut carbon emissions by 1,700 tons a year and saved 30,000 MBtus of energy annually. 

Cutting Costs and Boosting Efficiency

Cutting energy costs requires a few investments of time and money initially, but your energy cost savings will make up for that investment down the road. Additionally, your facility will become more efficient, which can raise profits effortlessly. Conserving energy helps the environment and your company. Start on conservation now to see the benefits of saving energy in your facility.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 16 July 2018

Yale researchers identify target for novel malaria vaccine


A Yale-led team of researchers have created a vaccine that protects against malaria infection in mouse models, paving the way for the development of a human vaccine that works by targeting the specific protein that parasites use to evade the immune system. The study was published by Nature Communications.

Malaria is the second leading cause of infectious disease worldwide, and took more than a half million lives in 2013. To date, no completely effective vaccine exists, and infected individuals only develop partial immunity against disease symptoms. In a prior study, senior author Richard Bucala, M.D. described a unique protein produced by malaria parasites, Plasmodium macrophage migration inhibitory factor (PMIF), which suppresses memory T cells, the infection-fighting cells that respond to threats and protect the body against reinfection.

In the new study, Bucala and his co-authors collaborated with Novartis Vaccines, Inc. to test an RNA-based vaccine designed to target PMIF. First, using a strain of the malaria parasite with PMIF genetically deleted, they observed that mice infected with that strain developed memory T cells and showed stronger anti-parasite immunity.

Next, the research team used two mouse models of malaria to test the effectiveness of a vaccine using PMIF. One model had early-stage liver infection from parasites carried by mosquitos, and the other, a severe, late-stage blood infection. In both models, the vaccine protected against reinfection. As a final test, the researchers transferred memory T cells from the immunized mice to “naïve” mice never exposed to malaria. Those mice were also protected.

The research shows, first, that PMIF is critical to the completion of the parasite life cycle because it ensures transmission to new hosts, said the scientists, noting it also demonstrates the effectiveness of the anti-PMIF vaccine.

“If you vaccinate with this specific protein used by the malaria parasite to evade an immune response, you can elicit protection against re-infection,” said Bucala. “To our knowledge, this has never been shown using a single antigen in fulminant blood-stage infection.”

The next step for the research team is to develop a vaccine for individuals who have never had malaria, primarily young children. “The vaccine would be used in children so that they would already have an immune response to this particular malaria product, and when they became infected with malaria, they would have a normal T cell response, clear the parasite, and be protected from future infection,” he stated.

The researchers also noted that because the PMIF protein has been conserved by evolution in different malaria strains and targets a host pathway, it would be virtually impossible for the parasite to develop resistance to this vaccine. Numerous other parasitic pathogens also produce MIF-like proteins, said the scientists, suggesting that this approach may be generalizable to other parasitic diseases — such as Leishmaniasis, Hookworm, and Filariais — for which no vaccines exist.
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 15 July 2018

New class of antibiotics to combat drug resistance


A new class of antibiotic has been discovered. The chemical kills bacteria by binding to ribosome. This disrupts protein synthesis, and stops the microbial cell from replicating. This is a step forward in the search for new antimicrobials.

Scientists from the University of Illinois at Chicago have highlighted a potential new class of antibiotics. These compounds appear effective at treating a range of current antimicrobial drug-resistant infections.

The new class of antibiotics, called odilorhabdins, are promising for two reasons. Firstly, the compound has a distinct way of killing bacteria. Secondly, the source of the compound is unusual. This strengthens the podetial use, should the compound be commercialized, for tackling hard-to-treat bacterial infections.

In terms of the atypical source for the chemicals, they are produced by symbiotic bacteria found only in soil-dwelling nematode worms. The bacteria colonize insects for food, and they also provide a degree or protection from bacteria that are pathogenic to the worms. This protection is through secreting the antibiotic.

In the last two decades, the speed at which bacteria are becoming resistant to current antibiotic treatments has significantly increased. This shift is threatening the ability of medical staff to carry out routine operations or organ transplants in the future. The problem has been compounded by microorganisms acquiring resistance to one antimicrobial or another, leading to multi-drug resistant microorganisms (the so-termed ‘super bugs’); and by the misuse of antibiotic by medical staff (improper prescribing) and farmers (in seeking leaner meats). The consequence has led to an imperative to finding new and effective antimicrobials.

As part of the process to find the new antibiotic, microbiologists screened 80 cultured strains of the bacteria for antimicrobial activity. Next, they isolated the active compounds, and proceeded to study their chemical structures. From this the researchers engineered more potent derivatives.

According to lead researcher Yury Polikanov there’s something important in the way that odilorhabdins kill bacteria: “Like many clinically useful antibiotics, odilorhabdins work by targeting the ribosome… but odilorhabdins are unique because they bind to a place on the ribosome that has never been used by other known antibiotics.”

With this mechanism, when odilorhabdins are introduced to the bacterial cells they impact the reading ability of the ribosome and this causes the ribosome to make mistakes as it creates new proteins. Trials to date have shown good effectiveness of the antibiotic against carbapenem-resistant Enterobacteriacae, a group that contains several antimicrobial resistant members.

The research has been published in the journal Molecular Cell. The research paper is titled “Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 14 July 2018

Diagnostic connectivity to combat antimicrobial resistance


The British government has entered into a partnership with FIND, a global non-profit dedicated to accelerating the development of diagnostic tests for diseases. This is to introduce digital technologies to combat the antimicrobial resistance problem.

The partnership, following the signing of a Memorandum of Understanding, establishes a three-year project focusing on connecting data from patients’ diagnostic test results into various national antimicrobial resistance surveillance program in low- and middle-income countries. This digital information will be to help address the rising problem of drug resistant infections.

The announcement about the collaboration was made on May, 22 2018 at the 71st World Health Assembly, which took place in Geneva, Switzerland. The project is being funded from U.K. Government’s Global Antimicrobial Resistance Innovation Fund. Here the British state will work with the Foundation for Innovative New Diagnostics (FIND).

The aim of the project, for the connectivity for diagnostics, is to improve worldwide surveillance of antimicrobial resistance. Here FIND and partner bodies will produce alternative tools and new solutions to connect information from antimicrobial resistant-related diagnostic testing of patients and to input the analyzed information into national surveillance programs operating in low- and middle-income countries. The aim is to greatly extend the scope of existing programs so they include routine hospital and community data.

The growing menace of antibiotic resistance presents the single most significant threat faced by the global population. The urgency is with profiling patterns of resistance, so that epidemiological patterns can be assessed, and with the development of new antibiotics. The risk is very real: human populations face the very real risk of a future without antibiotics. The implications of this are that life expectancy could fall due to people dying from diseases that are readily treatable today. For example, around 700,000 deaths each year are caused by drug-resistant pathogens worldwide.

The FIND strategy is that diagnostics plays an important role in helping to minimize the proliferation of drug-resistant bacteria, viruses, parasites and fungi. By using appropriate diagnostic tests, medical professionals can identify disease-causing pathogens and use this information to determine the presence of drug resistance. This is only possible through comprehensive databases, assessed using big data analytics.

An example is with drug resistant tuberculosis, here FIND are helping to develop better tests for case detection & drug susceptibility testing (sputum); improved tests for detection and triage (non-sputum); and latent-to-active prediction tests. These are often alternatives to lengthy culture based methods, offering rapid microbiological alternatives aimed at improved accuracy and faster time-to-result.

According to Catharina Boehme, who is the CEO of FIND: “Diagnostics are critical to tracking and monitoring diseases and the spread of drug resistance…Connecting diagnostics to surveillance systems at various levels from local to global will allow surveillance to be strengthened in LMICs – where the burden of infectious diseases is highest but data are currently limited.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 13 July 2018

Fluorescent silk kills harmful bacteria


A far-red fluorescent silk can kill harmful bacteria, as demonstrated in controlled trials. The developers see the material as both a biomedical and and an environmental remedy to combating harmful organisms and protecting patients.

The development of the new silk hybrid material (mKate2) comes from Purdue University. The material attacks bacteria when it is illuminated by a green light. The microbial-killing effect is due to the activation of a far-red fluorescent protein. The main application will be with bandages to help accelerate wound healing and to prevent infection. The aim was to come up with something safer than light-activate microbial killing technology, where organisms are killed using photocatalytic processes involving catalysts like titanium dioxide.

The material is formed from natural substrates. Here Purdue University worked with the Korean National Institute of Agricultural Research to create what are termed plasmonic photocatalyst-like biomaterials, to be used in conjunction with visible light, to kill pathogenic microbes.

While the use of silk may seem strange, according to lead researcher Professor Young Kim: "Silk is an ancient and well-known biomaterial. It doesn't have any issues with the human body. And the nice thing about green light is that it's not harmful -- the color corresponds to the strongest intensity of the solar spectrum."

To combine the benefits of silk and green light, the scientists inserted the gene for "mKate2" (which is a far-red fluorescent protein, into silk worms. By shining a green light on the hybrid generates reactive oxygen species. These are powerful radicals for breaking down organic contaminants and attacking the membrane and DNA of bacteria. In trials, significant reductions of pathogenic Escherichia coliwere seen.

The research into the material has been published in the journal Advanced Materials; the research paper is titled "Green-Light-Activated Photoreaction via Genetic Hybridization of Far-Red Fluorescent Protein and Silk."

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 12 July 2018

National Foundation for Infectious Diseases Announces 2018-2019 Board of Directors


The National Foundation for Infectious Diseases (NFID) is pleased to announce the 2018-2019 NFID Board of Directors and updated slate of officers, including NFID President Joseph A. Bocchini, Jr., MD, of Louisiana State University Health Sciences Center (LSUHSC) and President-Elect Patricia N. Whitley-Williams, MD, of the Rutgers Robert Wood Johnson Medical School in New Brunswick, NJ. Walter A. Orenstein, MD, Associate Director of the Emory Vaccine Center at Emory University in Atlanta, GA is Immediate Past-President.

Dr. Bocchini is Professor and Chair of the Department of Pediatrics at LSUHSC in Shreveport, LA, where he also serves as Medical Director of the Children’s Hospital and as a member of the Section of Pediatric Infectious Diseases. Dr. Bocchini has been a practicing physician for more than 45 years.

“It is an honor for me to assume the position of President of the National Foundation for Infectious Diseases,” said Dr. Bocchini. “As a practicing pediatrician and father of four daughters, the NFID mission of providing education to both healthcare professionals and the public on the causes, prevention, and treatment of infectious diseases is very important to me and I welcome the opportunity to guide the organization in the continued pursuit of its mission.”

Dr. Bocchini is a past chair of the Committee on Infectious Diseases of the American Academy of Pediatrics and a past member of the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices. He is a member of the American Society of Microbiology, Pediatric Infectious Diseases Society, American Pediatric Society, and the Academic Pediatric Association. He is a member of the Editorial Board of Infectious Diseases in Children. Dr. Bocchini received his MD from St. Louis University School of Medicine. He completed a residency in Pediatrics at the University of Connecticut and a fellowship in Pediatric Infectious Diseases at The Johns Hopkins University.

Dr. Whitley-Williams is Professor of Pediatrics and Chief of the Division of Pediatric Allergy, Immunology and Infectious Diseases at Rutgers. She is a liaison member of the CDC Advisory Committee on Immunization Practices and has served as a member of the Advisory Committee for the Elimination of Tuberculosis at CDC and the National Vaccine Advisory Committee of the Department of Health and Senior Services as well as the American Academy of Pediatrics Committee on Pediatric AIDS. Dr. Whitley-Williams has participated in the development of the national guidelines for the reduction of perinatal HIV transmission as a member of the Department of Health and Senior Services/Public Health Service Perinatal HIV Guidelines Working Group. Her interests include pediatric HIV infection/AIDS, tuberculosis in children and childhood immunization.

Other new Board members are Sara E. Cosgrove, MD, Johns Hopkins University School of Medicine; Ruth Lynfield, MD, Minnesota Department of Health; and Cynthia Pellegrini, March of Dimes. The complete list of 2018-2019 NFID Board of Directors is below. This esteemed group of public health leaders officially began responsibilities on July 1, 2018.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 11 July 2018

Enzyme discovery could help in fight against TB


An enzyme structure discovery made by scientists at the University of Warwick could help to eradicate tuberculosis (TB)

Research by a team led by Dr Elizabeth Fullam, has revealed new findings about an enzyme found in Mycobacterium tuberculosis (Mtb) the bacterium that causes TB.

TB causes more deaths than any other infectious disease, including from HIV and malaria. In 2016 there were 10.4 million new cases of TB and 1.7 million people died. The rise in cases of TB that are resistant to the current therapies that are available means that there is an urgent need to develop new TB therapeutics.

Mtb is a highly unique bacterium and is enclosed within a distinctive cell wall that is comprised of unusual sugars and lipids which protect the bacteria from the host environment. Disruption of essential pathways involved in the assembly of the Mtb cell wall is an attractive approach for new TB drugs.

The team found a key structural motif in the tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA) enzyme. Attacking this structural motif through the design and exploitation of new molecules will enable scientists to inhibit this critical pathway and kill TB.

Using the X-ray facilities at the Diamond Light Source, Harwell, they were provided with detailed molecular insights into how the NagA enzyme generates important precursors that are involved in Mtb cell wall biosynthesis and metabolism.

Dr Fullam, who is a Sir Henry Dale Fellow at the University of Warwick’s School of Life Sciences, said: “Tuberculosis is a major global health problem and the current drugs that we use today are over 40 years old. It is therefore vital that we discover new therapeutic agents to combat TB. In our studies, we have investigated the role of an enzyme in Mtb called NagA. This enzyme is a promising drug target as it is at a crucial metabolic chokepoint in Mtb. This means that a molecule that stops the enzyme from working would be an effective strategy for a drug and therefore it is critical to understand its function.

“Our group has identified a weak point within this protein that we can target and will now enable us to design specific molecules to block its function”

Using a range of biochemical and biophysical checks to determine the substrate specificity for the Mtb NagA enzyme they found a unique structural feauture in the Mtb NagA enzyme.This has revealed a molecular image of the protein and provides a platform to allow scientists to design new drugs that will hopefully inhibit this vital pathway and kill TB.

The research ‘Structural and functional determination of homologs of the Mycobacterium tuberculosis N-acetylglucosamine-6-phosphate deacetylase (NagA)’ is published in the Journal of Biological Chemistry

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 10 July 2018

Big data from world's largest citizen science microbiome project


Researchers at University of California San Diego School of Medicine and collaborators have published the first major results from the American Gut Project, a crowdsourced, global citizen science effort. The project, described May 15 in mSystems, is the largest published study to date of the human microbiome -- the unique microbial communities that inhabit our bodies.

This publication provides the largest public reference database of the human gut microbiome, which may help drive many future microbiome studies. What's more, according to the research team, the success of the American Gut Project validates citizen science as a practical model for engaging the public in research.

Here are a few observations that have emerged so far:

Diet. The number of plant types in a person's diet plays a role in the diversity of his or her gut microbiome -- the number of different types of bacteria living there. No matter the diet they prescribed to (vegetarian, vegan, etc.), participants who ate more than 30 different plant types per week (41 people) had gut microbiomes that were more diverse than those who ate 10 or fewer types of plants per week (44 people). The gut samples of these two groups also differed in the types of molecules present.

Antibiotics. The gut microbiomes of American Gut Project participants who reported that they took antibiotics in the past month (139 people) were, as predicted, less diverse than people who reported that they had not taken antibiotics in the last year (117 people). But, paradoxically, people who had taken antibiotics recently had significantly greater diversity in the types of chemicals in their gut samples than those who had not taken antibiotics in the past year.


The participants who ate more than 30 plants per week also had fewer antibiotic resistance genes in their gut microbiomes than people who ate 10 or fewer plants. In other words, the bacteria living in the guts of the plant-lovers had fewer genes that encode the molecular pumps that help the bacteria avoid antibiotics. This study didn't address why this might be the case, but the researchers think it could be because people who eat fewer plants may instead be eating more meat from antibiotic-treated animals or processed foods with antibiotics added as a preservative, which may favor the survival of antibiotic-resistant bacteria.

Mental health. The American Gut Project researchers also examined the gut microbiomes of 125 people who reported having a mental health disorder, such as depression, schizophrenia, post-traumatic stress disorder (PTSD) or bipolar disorder. They matched each of these participants to individuals who did not have a mental health disorder, but did have other major factors in common, such as country, age, gender and body mass index. The team found that people with a mental disorder had more in common with other people with mental disorders, in terms of the bacteria makeup of their gut microbiomes, than they did with their mentally healthy pairs. The observation held true in both U.S. and U.K. populations, in males and females, and across age groups. In addition, the research team found some indications that specific bacteria types may be more common in people with depression than people who do not have the condition.

See:

Daniel McDonald et al. American Gut: an Open Platform for Citizen Science Microbiome ResearchmSystems, 2018; 3 (3): e00031-18 DOI: 10.1128/mSystems.00031-18

Posted by Dr. Tim Sandle

Monday, 9 July 2018

New lineage of microbes living in Yellowstone


Montana State University scientists have found a new lineage of microbes living in Yellowstone National Park's thermal features that sheds light on the origin of life, the evolution of archaeal life and the importance of iron in early life.

The scientists called the new archaeal lineage Marsarchaeota after Mars, the red planet, because these organisms thrive in habitats containing iron oxides. Within Marsarchaeota, they discovered two main subgroups that live throughout Yellowstone and thrive in hot, acidic water where iron oxide is the main mineral. One subgroup lives in water above 122 degrees Fahrenheit, and the other lives in water above 140 to 176 degrees. The water is about as acidic as grapefruit juice. Their microbial mats are red because of the iron oxide.

Archaea is one of the three domains of life, the others being bacteria and eukaryotes. Like bacteria, archaea are single-cell organisms. The eukaryote domain contains more cellularly complex organisms, such as humans, other animals, plants and fungi.

See:

Zackary J. Jay, Jacob P. Beam, Mensur Dlakić, Douglas B. Rusch, Mark A. Kozubal, William P. Inskeep. Marsarchaeota are an aerobic archaeal lineage abundant in geothermal iron oxide microbial matsNature Microbiology, 2018; DOI: 10.1038/s41564-018-0163-1

Posted by Dr. Tim Sandle

Sunday, 8 July 2018

How the gut influences neurologic disease


A study published this week in Nature sheds new light on the connection between the gut and the brain, untangling the complex interplay that allows the byproducts of microorganisms living in the gut to influence the progression of neurodegenerative diseases. Investigators from Brigham and Women's Hospital (BWH) have been using both animal models and human cells from patients to tease out the key players involved in the gut-brain connection as well as in the crosstalk between immune cells and brain cells. Their new publication defines a pathway that may help guide therapies for multiple sclerosis and other neurologic diseases.

The new research focuses on the influence of gut microbes on two types of cells that play a major role in the central nervous system: microglia and astrocytes. Microglia are an integral part of the body's immune system, responsible for scavenging the CNS and getting rid of plaques, damaged cells and other materials that need to be cleared. But microglia can also secrete compounds that induce neurotoxic properties on the star-shaped brain cells known as astrocytes. This damage is thought to contribute to many neurologic diseases, including multiple sclerosis.

See:

Veit Rothhammer, Davis M. Borucki, Emily C. Tjon, Maisa C. Takenaka, Chun-Cheih Chao, Alberto Ardura-Fabregat, Kalil Alves de Lima, Cristina Gutiérrez-Vázquez, Patrick Hewson, Ori Staszewski, Manon Blain, Luke Healy, Tradite Neziraj, Matilde Borio, Michael Wheeler, Loic Lionel Dragin, David A. Laplaud, Jack Antel, Jorge Ivan Alvarez, Marco Prinz, Francisco J. Quintana. Microglial control of astrocytes in response to microbial metabolites. Nature, 2018; DOI: 10.1038/s41586-018-0119-x

Posted by Dr. Tim Sandle

Saturday, 7 July 2018

Exploration of diverse bacteria signals big advance for gene function prediction


Scientists have developed a workflow that enables large-scale, genome-wide assays of gene importance across many conditions. The study, 'Mutant Phenotypes for Thousands of Bacterial Genes of Unknown Function,' has been published in the journal Nature and is by far the largest functional genomics study of bacteria ever published.

Tested on nearly three dozen bacteria from various genera, the workflow combined high-throughput genetics and comparative genomics to identify mutant phenotypes for thousands of genes with previously unknown functions.

The team worked with 32 bacteria, including plant-growth promoting bacteria and a cyanobacterium relevant for biofuels production, as well as bacteria involved in bioremediation.

The data set is publicly accessible for comparative analyses at fit.genomics.lbl.gov, a web workbench developed by Morgan Price, the study's lead author, who has also developed powerful tools such as PaperBlast to help interpret results.

See:

Morgan N. Price, Kelly M. Wetmore, R. Jordan Waters, Mark Callaghan, Jayashree Ray, Hualan Liu, Jennifer V. Kuehl, Ryan A. Melnyk, Jacob S. Lamson, Yumi Suh, Hans K. Carlson, Zuelma Esquivel, Harini Sadeeshkumar, Romy Chakraborty, Grant M. Zane, Benjamin E. Rubin, Judy D. Wall, Axel Visel, James Bristow, Matthew J. Blow, Adam P. Arkin, Adam M. Deutschbauer. Mutant phenotypes for thousands of bacterial genes of unknown functionNature, 2018; DOI: 10.1038/s41586-018-0124-0

Posted by Dr. Tim Sandle

Friday, 6 July 2018

The Last Days of the Blue-Blood Harvest


An interesting article in The Atlantic on the use of the horse-shoe crab for manufacturing endotoxin test reagents.

Some extracts of interest:

“Every year, more than 400,000 crabs are bled for the miraculous medical substance that flows through their bodies—now pharmaceutical companies are finally committing to an alternative that doesn't harm animals.”

Horseshoe crabs bled for the biomedical use in the United States are returned to the ocean, but an estimated 50,000 also die in the process every year.”

“A synthetic substitute for horseshoe-crab blood has been available for 15 years. This is a story about how scientists quietly managed to outdo millions of years of evolution, and why it has taken the rest of the world so long to catch up.”

“On the regulatory side, the European Pharmacopoeia added recombinant factor C as an accepted bacterial-toxin test in 2016, paving the way for change in the United States. A number of pharmaceutical companies, most notably Eli Lilly, have compared the effectiveness of recombinant factor C and LAL”

See the Atlantic - https://www.theatlantic.com/amp/article/559229

Posted by Dr. Tim Sandle

Thursday, 5 July 2018

Uncovering mechanism of action for a class of pore-forming bacterial toxins


Pore-forming toxins are bacterial poisons that destroy cells by creating holes in the cell membranes. Many bacterial pathogens produce such toxins, including, for example, some strains of the intestinal bacterium Escherichia coli as well as Yersinia enterolitica, a pathogen related to the plague. They attack all kinds of organisms with the help of their toxins -- from plants to insects, and even humans.

Scientists all over the world are trying to understand how these toxins produce the fatal openings in cell membranes in hope of one day inhibiting the pathogenic, pore-forming poisons.

After several years of research, an interdisciplinary team from the Technical University of Munich managed to elucidate the mode of action of a toxin subspecies in which two components interact to develop the deadly effect.

See:

Bastian Bräuning, Eva Bertosin, Florian Praetorius, Christian Ihling, Alexandra Schatt, Agnes Adler, Klaus Richter, Andrea Sinz, Hendrik Dietz, Michael Groll. Structure and mechanism of the two-component α-helical pore-forming toxin YaxABNature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04139-2

Posted by Dr. Tim Sandle

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