Saturday, 18 May 2019

Global microbial signatures for colorectal cancer

Patients with colorectal cancer have the same consistent changes in the gut bacteria across continents, cultures, and diets -- a team of international researchers find in a new study. The hope is the results in the future can be used to develop a new method of diagnosing colorectal cancer. This is based on research from the University of Copenhagen The Faculty of Health and Medical Sciences.

Cancers have long been known to arise due to environmental exposures such as unhealthy diet or smoking. Lately, the microbes living in and on our body have entered the stage as key players. But the role that gut microbes play in the development of colorectal cancer -- the third most common cancer worldwide -- is unclear. To determine their influence, association studies have aimed to map how the microbes colonizing the gut of colorectal cancer patients are different from those that inhabit healthy subjects.

Now, researchers have analysed multiple existing microbiome association studies of colorectal cancer together with newly generated data. Their meta-analyses establish disease-specific microbiome changes, which are globally robust -- consistent across seven countries on three continents -- despite differences in environment, diet and life style.

READ MORE: Killer immune cells that halt malaria could hold key to new vaccines

The study led by UCPH and EMBL scientists focuses on a process in which certain gut bacteria turn bile acids that are part of our digestive juices into metabolites that can be carcinogenic. A related study from the University of Trento shows how certain classes of bacteria degrade choline, an essential nutrient contained in meat and other foods, and turn it into a potentially dangerous metabolite. This metabolite has previously been shown to increase cardiovascular disease risk, and can now also be linked to colorectal cancer.

One of the challenges of metagenomic studies, which are based on genetic material from microbes in environmental samples such as stool, is to link genetic fragments to the various microbial organisms they belong to. The goal of this so-called taxonomic profiling task is to identify and quantify the bacterial species present in the sample.

The role of gut microbes in colorectal cancer still needs to be established. If the changes in the microbiome play a role in developing the cancer, they could also be a therapeutic target. Therefore, Manimozhiyan Arumugam hopes that there will be more focus on the role of microbiome in diseases and that researchers will recognize the advantages of collecting microbiome samples, for example, in large cohorts.

Journal reference:

Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nature Medicine, 2019; DOI: 10.1038/s41591-019-0406-6
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 17 May 2019

Tackling challenge of antifungal resistance

New work is helping develop a better understanding of the growing threat posed by antifungal drug resistance. Invasive aspergillosis is a devastating disease caused by breathing in small airborne spores of the fungus Aspergillus fumigatus and it is a condition where drug resistance has been encountered. They have just released a paper revealing how they have been able to identify a previously uncharacterized genetic mutation in clinical isolates that leads to resistance.

Invasive aspergillosis is a devastating disease caused by breathing in small airborne spores of the fungus Aspergillus fumigatus and it is a condition where drug resistance has been encountered.

In a healthy person these spores are destroyed by the body's immune system but in those with a weakened immune system -- such as following organ transplantation or in someone with a lung condition such as asthma or cystic fibrosis -- they can trigger a range of problems including infections.

READ MORE: Fungal spore 'death clouds' key in gypsy moth fight

Every year aspergillosis leads to more than 200,000 life-threatening infections and increasingly resistance to vital antifungal drug treatments makes those infections harder to treat.

National Institutes of Health (USA) funding supported a collaboration between the University of Tennessee, the University of Texas and Swansea University as part of a $2 million, five-year research programme. This support enabled investigation of resistance to the triazole class of antifungal drugs used for treating the disease

A new paper shows how researchers have been able to identify a previously uncharacterised genetic mutation in clinical isolates that leads to resistance.

Journal reference:

Jeffrey M. Rybak, Wenbo Ge, Nathan P. Wiederhold, Josie E. Parker, Steven L. Kelly, P. David Rogers, Jarrod R. Fortwendel. Mutations in hmg1, Challenging the Paradigm of Clinical Triazole Resistance in Aspergillus fumigatus. mBio, 2019; 10 (2) DOI: 10.1128/mBio.00437-19
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Endotoxin and Pyrogen survey

Testing for Endotoxins and Pyrogens?

Take a short survey (10 minutes) to help us understand your endotoxin and pyrogen testing needs.

For the first 100 respondents, a donation of 10 € per respondent will be given to the Seeding Labs charity organization.

To take the survey, please go to: 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 16 May 2019

probiotic could disrupt Crohn's disease biofilms

A probiotic has been found to help weaken stubborn microbial biofilm communities in the gut that can worsen symptoms. Researchers from Case Western Reserve University report.

Probiotics typically aim to rebalance bacteria populations in the gut, but new research suggests they may also help break apart stubborn biofilms. Biofilms are living microbial communities -- they provide a haven for microbes and are often resistant to antibiotics. A new study describes a specific probiotic mix that could help patients with gastrointestinal diseases avoid harmful biofilms that can worsen their symptoms.

The study evaluated the ability of a novel probiotic to prevent and treat biofilms containing yeast and bacteria -- in particular, species that thrive in damaged guts. Biofilms can contain an infectious polymicrobial mix of bacteria and fungi all living together underneath a thick protective slime. These polymicrobial communities are resistant to antibiotics, but can be antagonized by other microbes. Other microbes living in the gut -- or administered via probiotics -- can help break apart biofilms, according to the new study.

READ MORE: Probiotics Shown to Dramatically Improve IBS Gut Symptom

In a series of experiments researchers grew yeast (Candida species) and bacteria (Escherichia coli and Serratia marcescens) into biofilms. They then exposed the biofilms to a promising probiotic mix identified in a previous study -- one part yeast, three parts bacteria, and a small amount of amylase (an enzyme found in saliva). Microscope images showed biofilms exposed to the mix were looser-knit communities that were overall thinner and weaker than untreated biofilms.

The researchers found the probiotic worked in part by weakening yeast living in young biofilms. The yeast inside the biofilms were stunted in growth and did not form reproductive structures that help seed new biofilm growth and expansion. The researchers concluded their novel probiotic mix might help prevent harmful biofilms in people with inflammatory bowel disease or other gastrointestinal conditions.

Journal reference:

Christopher L. Hager, Nancy Isham, Kory P. Schrom, Jyotsna Chandra, Thomas McCormick, Masaru Miyagi, Mahmoud A. Ghannoum. Effects of a Novel Probiotic Combination on Pathogenic Bacterial-Fungal Polymicrobial Biofilms. mBio, 2019; DOI: 10.1128/mBio.00338-19
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 15 May 2019

Deep microbes' key contribution to Earth's carbon cycle

This new finding, from the Tokyo Institute of Technology, highlights the importance of microorganisms in the geochemistry of natural gas and petroleum.

Hydrocarbons play key roles in atmospheric and biogeochemistry, the energy economy, and climate change. Most hydrocarbons form in anaerobic environments through high temperature or microbial decomposition of organic matter. Subsurface microorganisms can also 'eat' hydrocarbons, preventing them from reaching the atmosphere. Using a new technique, scientists show that biological hydrocarbon degradation gives a unique biological signature. These findings could help detect subsurface biology and understand the carbon cycle and its impact on climate.

The researchers fed propane to microorganisms in the lab to measure the specific 12C/13C signature produced these organisms, and measured the non-biological changes that occurred when propane is broken down at high temperatures, a process known as "cracking." They then used these baseline measurements to interpret natural gas samples from the US, Canada and Australia, allowing them to detect the presence of microorganisms using propane as "food" in natural gas reservoirs, and to quantify the amount of hydrocarbons eaten by microorganisms.

READ MORE: Carbon monoxide improves effectiveness of antibiotic

When the researchers began analyzing samples from the bacterial simulation experiments, they matched perfectly what we observed in the field, suggesting the presence of propane degrading bacteria in the natural gas reservoirs.
Thus, this study revealed the presence of microorganisms that would have been difficult to detect using conventional methods, and opens a new window to understanding global hydrocarbon cycling.

Journal reference:

Intramolecular isotopic evidence for bacterial oxidation of propane in subsurface natural gas reservoirs. Proceedings of the National Academy of Sciences, 2019; 116 (14): 6653 DOI: 10.1073/pnas.1817784116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 14 May 2019

Hospitals will be moving to digital pathology: Study

The take-up of digital pathology technology is expected to increase during the next decade and the main adopters of this technology will be healthcare organizations, such as hospitals and diagnostic laboratories, according to a new report.

As well as digital technologies in general, the healthcare sector will be enhancing digital images with artificial intelligence to help pathologists to detect key signs earlier or to help with greater accuracy.

Other advantages that will arise from such technology are centered on decreasing turnaround time, prioritizing critical cases, and improving overall patient outcomes. To do so will involve innovating and developing tools for primary and secondary analysis.

These are key highlights from a new report issued by Frost & Sullivan. The report is titled “Digital Pathology: Roadmap to the Future of Medical Diagnosis.” The types of technologies within this space are digital whole slide scanning, digital imaging solutions, and offering a digital data repository, which can be subject to big data analysis.
Many of these technologies will enable researchers to access databases from the cloud and for hospitals to collaborate together, in terms of sharing images. It is also possible to send an image around the world so that a second opinion can be given from a specialist consultant.

The report charts how the regulatory landscape has shifted and there is proven method qualification to show that digital systems are very effective, resulting in the barriers to technology take-up and implementation being lower.

As an example, the digital pathology system, and artificial intelligence platform, OsteoDetect has gained approval from the U.S. Food and Drug Administration (FDA). The technology is used for the detection of distal radius fracture.

Commenting on the report, Deepak Jayakumar, Senior Research Analyst, TechVision states: “Artificial intelligence has the potential to analyze big data and find patterns and insights that could enhance patient outcomes in the field of pathology. It can serve as a supplementary or a validation tool in imaging analytics for pathologists, and help process more slides in a shorter duration."

He goes on to assess how these technologies will appeal strongest to hospitals and diagnostic laboratories. A driver for this will be seeking cost optimization for end users. This can be realized via pay-per-use or Software-as-a-Service (SaaS) models. A side effect of this will be to disrupt traditional models within the healthcare system.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 13 May 2019

4 Cold Chain Logistics Trends Impacting Pharmaceuticals

When a drone is used for the first time to deliver an organ to a transplant recipient, you know big things are afoot in the pharmaceutical cold chain.

So what else drives growth in this field? And which technologies are coming to the forefront to make this critical industry safer and more efficient? Let's take a look at some answers.

A guest post from Megan Ray Nichols

1. Personalized Medicines

One of the greatest disruptions to medicine in recent memory — and the cold chain that powers the pharma industry — is personalized medicine. Also called "precision medicine," this is the practice of specifically tailoring (and even 3D-printing) medications and gene and cell therapies for use by smaller, more specific sets of patients. According to a 2017 report by the Personalized Medicine Coalition, the next five years will see a 69% increase in the number of precision drugs coming to market.

This is a huge opportunity for cold chain and logistics companies — but it also presents some roadblocks. These are small-batch medications that must be delivered within very tight deadlines. Compared with larger shipments and uniform temperature control requirements, the challenges speak for themselves. Some of these bespoke medications, including monoclonal antibodies, are more fragile than others and more susceptible to environmental hazards. Supply chain and logistics companies must stand ready with more efficient business models and more advanced thermal packaging. 

2. Blockchain and Traceability Requirements

Visibility and transparency are even more important in cold chain logistics than in any other supply chain. Various countries and emerging markets have different track-and-trace requirements, but technology can help cut through the noise and provide a standardized approach to supply chain transparency.

Blockchain presents a way for pharmaceutical companies to comply with increasingly and appropriately stringent government regulations concerning the transportation of pharmaceutical products. For example, the FDA's Drug Supply Chain Security Act lays out expectations for "electronic, interoperable systems" for recording and reporting information on drug shipments, with the goal of rooting out counterfeit products and streamlining the auditing and reporting processes. But these electronic systems require accurate and timely data to be of any use.

With that in mind, it will likely become the norm for logistics companies to employ blockchain and attach a cryptographically unique identifier to pharmaceutical shipments. This blockchain "token" collects information from origin to destination and cannot be altered once recorded. As a result, logistics companies can visualize their entire supply chain in the name of safety and authenticity. 

3. Data Everywhere and the IoT

Adoption of the Internet of Things is ramping up across the medical landscape. According to a DHL report entitled "The Future of Life Sciences and Healthcare Logistics," the health care IoT market will grow to $646 million in value by 2020. Cold chain and logistics companies drive a great deal of this growth.

As the demand for traditional and personalized medicine alike grows, companies must be more vigilant than ever about optimizing their manufacturing processes, insulating themselves against disruptions and forecasting demand. The IoT and Big Data are key allies in these challenges:

As an example, Bayer plans out its antihistamine supply chain roughly nine months in advance using analytics that incorporate information about climate patterns, customer demand and historical and geographical trends for conditions like hay fever. This ensures their products get to where they're needed most and stores don't run out during peak demand.

IoT-enabled manufacturing equipment can collect data all the way from production through to distribution and provide insights that lead to process optimizations. If there's a department creating a bottleneck, an inefficient vendor, or a not-quite-optimally-placed distribution hub, companies can find out about it and make timelier decisions and operational changes.

Pharmaceutical products must be kept at stable temperatures during storage and transit, or risk spoilage. Remote monitoring using the IoT and cloud-based intelligence platforms can track critical metrics for every shipment and every variable-temperature, ambient and freezer storage space, and alert personnel if conditions drop below or rise above optimal levels. It's not just about the 32- to 37-degree model anymore — facilities must be more flexible and we need technologies to support that flexibility.

Predicting demand, ironing out the kinks in manufacturing and having "eyes on" every shipment at every moment brings greater efficiency and safety to the cold chain than was ever possible before the IoT came to the fore. 

4. Mergers, Partnerships and Acquisitions

If there's an overriding mission across just about every industry, it's to reduce the time it takes for a customer to receive their order after they click "buy." The "on-demand" and "same-day" business models have already changed entertainment and eCommerce for good — and they're about to do the same for health care.

In 2018, Amazon, J.P. Morgan and Berkshire Hathaway announced a partnership called "Haven" and declared their intention to disrupt the health care industry. Immediately afterward, CVS, Walmart, Express Scripts and Cardinal Health stocks all plummeted. They lost billions of dollars in value overnight.

This isn't Amazon's only move that looks ready to shake up the cold chain industry. The retail giant also owns Whole Foods and more recently acquired PillPack — an online pharmacy — for a reported $1 billion.

Amazon doesn't have a monopoly on eCommerce, but they do enjoy a huge share of the pie. Just as importantly, their business model ushered in huge changes in customer expectations and omnichannel sales strategies when it comes to online selection and speed of delivery. All of the clues we mentioned seem to suggest that Amazon wants to use its influence to make significant changes to how pharmaceutical products are distributed, too.

When we try to catch a glimpse of the future of the pharmaceutical supply chain, it looks more and more like direct-to-patient and direct-to-hospital delivery will be the order of the day, for diagnostic tools and medical devices as well as for more time-sensitive medication purchases. Supply chain companies aren't going anywhere — indeed, the explosion in popularity of online pharmacies and even subscription-based business models likely means they'll be busier than ever — but wholesalers might slowly be squeezed out of the equation as tech giants like Amazon and others consolidate industry resources and reinvent consumer expectations.

No matter what, the cold chain will keep doing what it does best — getting pharmaceutical products into the hands of people who need them. But how it does so, and the tools it uses, are shaking up before our eyes.

Sunday, 12 May 2019

Why Is Fire Safety Training Important For Your Health?

Fire safety training seems like something that is just done because it’s a part of office protocol or even your home protocol, but fires are no joke and your health matters at the end of the day. Fire safety training can protect you and your health, and here, we’ll discuss why it matters, and some other elements that you may not even think about.

Guest post by Emily Bartels.

They Are Dangerous

Fires are incredibly dangerous, because they are hot, and the smoke in them can actually cause lung issues later on, including asthma and other breathing problems. they’re not just something that you overlook either, they can potentially put you and the entire office at risk. they’re more dangerous than you think, and the thing is, you want to make sure that you recognize these dangers. Fire safety training teaches you how to do this, and also how to tell when fires are occurring.  You could potentially save a life or lives by knowing the protocol, so think about that next time.

People Don’t Recognize Fire Hazards Usually

All fires begin with some source of heat mixing with a fuel, and for a fire to occur, you need to have oxygen. If you're working with anything related to heat, or even fuel, you’ll want fire safety training, because people usually don’t realize how simple it is to cause a fire.  For example, if you have a gas stove, you’re at risk for a household fire.  It’s that small, but it’s super important to understand this since it can be potentially dangerous.

You Need to Know How to Leave the Building Quickly

The reason why you need a fire safety plan and training is because you need to know how to leave a building in the event of a fire.  For example, if you're up on the fourth floor, what’s the quickest way down? what’s the alternate route in the event that you can’t use the mains stairwell? Where are the stairs? Where should you go if they’re blocked? Understanding this will help in the event that there is a fire because you can actually leave the building quickly.

In this as well, you can also identify any fire fighting gear, including a fire extinguisher, which, while it isn’t the ideal way to fight a fire, ti can shave off precious time if you have one so that you can escape. This can put your safety at the forefront, and save your life.

If you Work with Others, you Need to Know

It isn’t just the health and safety of yourself, but it’s of others too.  you’ll want to know of the best way to handle these fires, especially with other people. If you work in a hospital or nursing home for example, you’ll want to know how to get these people out of there, any risks associated with their bodies that may pose a problem, such as oxygen tanks, and how to get someone who is in a wheelchair out.  This, in turn, will help to protect others, and it will help make it much better for you as well. You can save the lives of others if you’re careful, and you’ll be able to get others out of here quickly.
Allows you to Be Proactive

With a fire safety plan, you’ll be able to become more proactive in the home or workplace. For example, you’ll want to keep the spaces cleaner, and from there, only smoke in designated areas, and always make sure everything that is flammable is kept away from work areas.  you’ll also want to perform regular maintenance on your machinery too, which is very important, and you’ll want to read the different sheets that improve the way that you handle your fire safety and any flammable equipment. It puts you more in charge, and that can help a lot.

Prevents Damages from Chemicals

One of the biggest causes of fires especially in the workplace is chemical fires. that’s because they’re not properly restored. But, with the right kind of training, you’ll be able to prevent this from getting worse and you’ll be able to, with the right fire safety training, keep everything out of the way, and make sure that these chemicals are properly stored in places where there isn’t any heat being generated to these chemicals, which can act as a fuel. This also prevents other workplace accidents too.

When it comes to fire safety training, the right tactics are so important, so make sure that you always have these in place when you’re working on fire safety training, for it can help to make a change in the overall state of your office, and in turn, you’ll be able to prevent these fires and the like from getting worse, and also allow for you to have a better, more proactive plan of action.

Genetically engineering yeast to improve understanding of how cells work

Researchers have 'fine-tuned' a major cell signalling mechanism by rewriting DNA inside yeast cells to control how they respond to their environment.

The study, which was published recently by the journal Cell, has immediate biotechnology uses but could also have wider implications for healthcare research. It is hoped being able to alter how cells react will help scientists understand how diseased cells function and lead to modified cells being used to treat patients.

Academics from the University of Cambridge and Imperial College London, in collaboration with AstraZeneca, used mathematical modelling and genome engineering to edit yeast cells to help scientists control not just what the cells sense but how they react to what they sense in a more desirable way.

Yeast was chosen because it shares key characteristics with human cells -- most importantly that it can sense its environment using G protein-coupled receptors (GPCRs).

GPCRs are receptors which enable cells to sense chemical substances such as hormones, poisons, and drugs in their environment. The cells read their environment and sense the levels of hormones such as adrenalin, serotonin, histamine and dopamine. They can also act as light, smell and flavour receptors with some located on the tongue to give us our sense of taste.

READ MORE: Yeast engineered to manufacture complex medicine

There are around 800 different GPCRs in our bodies and around half of all medication acts using these receptors -- including beta blockers, antihistamines and various kinds of psychiatric drugs. But not enough is known about how GPCR signalling works.

One of the difficulties for researchers is that DNA variations can have an impact on the signalling network and determining how parts of the DNA affect this is a major challenge.

The Cambridge team created a mathematical model of the yeast cell with varied concentrations of different cell components and found the optimum levels for the most efficient signalling of each one. This knowledge was then used to genetically modify cells by a team of researchers at Imperial College London.

Research paper:

William M. Shaw, Hitoshi Yamauchi, Jack Mead, Glen-Oliver F. Gowers, David J. Bell, David Öling, Niklas Larsson, Mark Wigglesworth, Graham Ladds, Tom Ellis. Engineering a Model Cell for Rational Tuning of GPCR Signaling. Cell, 2019; DOI: 10.1016/j.cell.2019.02.023

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 11 May 2019

Compound that kills drug-resistant fungi is isolated from ant microbiota

Antimicrobial and antifungal resistance, which describe the ability of bacteria and other pathogens to resist the effects of drugs to which they were once sensitive, is a major public health problem worldwide.

The idea of the new study was to isolate bacteria that live in symbiosis with leafcutting ants of the genus Atta and to look for natural compounds with the potential to yield new drugs.

By pursuing this strategy, a research group led by Monica Tallarico Pupo, Professor of Medicinal Chemistry at the University of São Paulo's Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP), and Jon Clardy, Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School in the US, discovered cyphomycin, which, when tested in vitro and in vivo, was shown to be capable of killing fungi that cause diseases in humans and are resistant to currently available drugs.

Many antibiotics originate from compounds produced by bacteria found in soil. Most of these bacteria belong to the genus Streptomyces. The researchers decided to investigate this same group of filamentous bacteria in insect bodies. Their hypothesis was that if the bacteria help insects defend against pathogens, they might play the same role in humans.

Specimens were collected by collaborators from the US, Costa Rica and Panama. In addition to leafcutting ants of the tribe Attini, butterflies, wasps, bees and moths were included, for a total of 1,400 insects.

READ MORE: Fungus provides powerful medicine in fighting honey bee viruses

After the insects were collected, the bacteria found in their bodies were isolated, purified in the laboratory, and tested in vitro against microorganisms that act as pathogens in humans. The species that proved most effective against these pathogens were selected for metabolomic analysis -- to characterize the metabolites they produce and identify the most active of these -- and for phylogenetic studies, in which gene sequencing indicated to what extent the insect-associated bacteria resembled the strains of Streptomyces that live in soil.

The researchers combined chemometrics and liquid chromatography coupled with mass spectrometry to profile the compounds produced by the insect microbiota. The aim was to identify the Streptomyces strains that produce a distinctive chemistry -- in other words, to find compounds quite different from those synthesized by soil bacteria. In this way, we increased the likelihood of finding a genuinely innovative molecule.

The compounds shown to be most effective by these rigorous methods were tested again, in vitro and in mice, against pathogens resistant to the drugs used in clinical practice.

Cyphomycin was not effective against bacteria but proved capable of combating infection by Aspergillus fumigatus, the fungus most frequently found in hospital-acquired infections and the cause of aspergillosis, a disease with an attributable mortality as high as 85% even after antifungal treatment.

When administered to laboratory animals, cyphomycin also combated infection by Candida glabrata and C. auris, fungi that cause candidiasis in humans and are resistant to existing drugs.

Research paper:

The antimicrobial potential of Streptomyces from insect microbiomes. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-08438-0

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 10 May 2019

Virus-infected bacteria could provide help in the fight against climate change

Viruses don't always kill their microbial hosts. In many cases, they develop a mutually beneficial relationship: the virus establishes itself inside the microbe and, in return, grants its host with immunity against attack by similar viruses.

Understanding this relationship is beneficial not only for medical research and practical applications but also in marine biology, says Alison Buchan, Carolyn W. Fite Professor of Microbiology at the University of Tennessee, Knoxville.

"Marine microbes are uniquely responsible for carrying out processes that are essential for all of earth's biogeochemical cycles, including many that play a role in climate change," she said.
Buchan has explained some of these interactions at the annual meeting of the American Association for the Advancement of Science in Washington, D.C.

Her talk, "It's Only Mostly Dead: Deciphering Mechanisms Underlying Virus-Microbe Interactions," will be part of the scientific session titled Viruses, Microbes and Their Entangled Fates.

The function of a microbial community is in large part dictated by its composition: what microbes are present and how many of each.

Within the community, bacteria compete with one another for resources. In the course of this fight, some bacteria produce antibiotics and use them against other types of bacteria. This kind of interaction has been known for some time.

But there is another fight strategy that scientists like Buchan are just now considering: bacteria might use the viruses that infect them as weapons against other types of microbes.
"We have recently discovered that while they are in the process of dying, microbes can produce new viruses that then go to attack their original invader. This is a form of resistance we had not observed before," said Buchan.

This type of competitive interaction, Buchan said, is important for stabilizing the size of microbial populations in marine systems. This balance may be crucial for biogeochemical processes, including many related to climate change.

During her presentation, Buchan shared the stage with Joshua Weitz, professor or theoretical ecology and quantitative biology at the Georgia Institute of Technology, and Matthew Sullivan, associate professor of microbiology and civil, environmental, and geodetic engineering at the Ohio State University.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 9 May 2019

The rules behind virus scaffold construction

A team of researchers including Northwestern Engineering faculty has expanded the understanding of how virus shells self-assemble, an important step toward developing techniques that use viruses as vehicles to deliver targeted drugs and therapeutics throughout the body.

By performing multiple amino acid substitutions, the researchers discovered instances of epistasis, a phenomenon in which two changes produce a behavior different from the behavior that each change causes individually.

"We found occurrences where two separate single amino acid changes caused the virus shell to break or become really unstable, but making both changes together produced a stable structure that functioned better than ever," said Danielle Tullman-Ercek, associate professor of chemical and biological engineering at the McCormick School of Engineering.

The latest research builds on the team's progress by using SyMAPS to analyze multiple amino acid changes within the MS2 particle, a requirement to effectively manipulate virus shells in the future, Tullman-Ercek said. Researchers studied every double amino acid combination along a polypeptide loop located within the MS2 scaffold and measured how the virus scaffold was affected.

One factor producing epistasis was balancing the amino acid charges that were substituted, said Tullman-Ercek, a member of Northwestern's Center for Synthetic Biology. Swapping two positively charged amino acids, for instance, caused the particle to repel and break apart, but balancing a single positive amino acid change with a separate negative charge compensated the switch and preserved stability.


Emily C. Hartman, Marco J. Lobba, Andrew H. Favor, Stephanie A. Robinson, Matthew B. Francis, Danielle Tullman-Ercek. Experimental Evaluation of Coevolution in a Self-Assembling Particle. Biochemistry, 2018; 58 (11): 1527 DOI: 10.1021/acs.biochem.8b00948

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 8 May 2019

New sterile manufacturing guidance published by EMA

The European Medicines Agency (EMA) has published the final version of “Sterilisation of the medicinal product, active substance, excipient and primary container” (EMA/CHMP/CVMP/QWP/850374/2015), which first appeared in draft form in 2016. The document was published on 8th March 2019 and becomes effective from 1st October 2019.

The guidance describes the selection of appropriate methods of sterilisation for sterile products. The guidance discusses the importance of terminal sterilisation and the use of alternative methods for producing sterile products when terminal sterilisation cannot be undertaken (that is using sterilising filtration or aseptic processing, or a combination of the two). Where terminal sterilisation cannot be adopted, a robust rationale needs to be provided. For new products, the document outlines the appropriate decision-making process that is to be followed and the requirements needed for the marketing authorisation application (or a variation application) for a new or updated medicinal product. Central to the decision-making process is risk assessment and risk acceptance, within the overall context of quality risk management.

I will be analysing the implications in a forthcoming review article.

For details, see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 7 May 2019

Bacterial contamination in household and office building tap water

Water is a source of concern for disseminating the bacteria Legionella pneumophila and Mycobacterium avium, which cause lung disease (legionellosis and pulmonary nontuberculous mycobacterium disease, respectively). A new study has examined the presence of these microbes in tap water from residences and office buildings across the United States.

The occurrence of L. pneumophila and M. avium was largely sporadic. Office buildings were prone to microbial persistence independent of building age and square footage. Microbial persistence at residences was observed in those older than 40 years for L. pneumophila and was rarely observed for M. avium.

The investigators noted that the lack of consistent detections reduces the potential to cause an outbreak among a family or group of workers.


M.J. Donohue, D. King, S. Pfaller, J.H. Mistry. The sporadic nature of Legionella pneumophila , Legionella pneumophila Sg1 and Mycobacterium avium occurrence within residences and office buildings across 36 states in the United States. Journal of Applied Microbiology, 2019; DOI: 10.1111/jam.14196

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 6 May 2019

Improper removal of personal protective equipment contaminates health care workers

More than one-third of healthcare workers were contaminated with multi-drug resistant organisms (MDRO) after caring for patients colonized or infected with the bacteria, according to a study published today in Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America. The study found that 39 percent of workers made errors in removing personal protective equipment (PPE), including gowns and gloves, increasing the incidence of contamination.

"Based on these findings, we should re-evaluate strategies for removing personal protective equipment, as well as how often healthcare workers are trained on these methods," said Koh Okamoto, MD, MS, a lead author of the study. "An intervention as simple as education about appropriate doffing of personal protective equipment may reduce healthcare worker contamination with multi-drug resistant organisms."

Researchers at Rush University Medical Center monitored 125 healthcare workers in four adult intensive care units who were caring for patients colonized or infected with a MDRO, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Researchers took more than 6,000 samples from healthcare workers' hands, gloves, PPE, and other equipment, such as stethoscopes and mobile phones, taking cultures before and after patient interaction.

Additionally, trained observers monitored the technique each worker used to put on and remove their PPE and tracked errors based on guidelines established by the Centers for Disease Control and Prevention. The CDC suggests two removal methods for PPE -- a gloves-first strategy, and an approach that removes gown and gloves together. Researchers also tracked a third method of removing the gown first. A significant majority of the healthcare workers had received training on appropriate methods for putting on and removing PPE within the past five years.

After patient contact, 36 percent of healthcare workers were contaminated with a MDRO. Contamination of healthcare workers' PPE was more common in settings of higher patient and environmental contamination. After removing their PPE, 10.4 percent were contaminated on their hands, clothes, or equipment.

Healthcare workers who made multiple errors when removing their PPE were more likely to be contaminated after a patient encounter, however the rate of making errors depended on the PPE removal method, with 72 percent of workers who used a glove-first removal making multiple errors. Examples of errors included touching the inside of the gown or glove with a gloved hand, touching the outside of the gown or glove with bare hands, and not unfastening the gown at the neck.

Given the high rate of hand contamination of those who used the gloves-first strategy, the authors recommend further research and possible reconsideration of this technique, as well as research to examine the impact of improved education for putting on and taking off PPE. Additionally, the authors note several limitations to their work, including the influence of observers on healthcare workers' practices and the potential that not all contamination was detected.


Koh Okamoto, Yoona Rhee, Michael Schoeny, Karen Lolans, Jennifer Cheng, Shivani Reddy, Robert A. Weinstein, Mary K. Hayden, Kyle J. Popovich. Impact of doffing errors on healthcare worker self-contamination when caring for patients on contact precautions. Infection Control & Hospital Epidemiology, 2019; 1 DOI: 10.1017/ice.2019.33

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 5 May 2019

Hidden proteins found in bacteria

Scientists at the University of Illinois at Chicago have developed a way to identify the beginning of every gene -- known as a translation start site or a start codon -- in bacterial cell DNA with a single experiment and, through this method, they have shown that an individual gene is capable of coding for more than one protein.

Historically, the generally taught scientific premise has been that each gene has one unique start site and is responsible for the creation of only one protein. However, the study, which is published in Molecular Cell, a leading journal on the topic of cellular processes, shows that some genes have more than one start site and can specify production of more than one functional protein.

Their method of identifying gene start sites relies on a common prescription drug called retapamulin, a topical antibiotic. Retapamulin, they showed for the first time, works by causing the ribosome, which reads genetic code, to become stalled at these start sites, inhibiting translation, a key part of the process by which the genetic code in DNA is used to create proteins.

UIC's Alexander Mankin and Nora Vázquez-Laslop led the research, which looked at E. coli cells in response to retapamulin in in vitro and in vivo experiments. The researchers found more than 100 E. coli genes, out of around 4,000, that could initiate protein synthesis at more than one site.

For further details, see:

Sezen Meydan, James Marks, Dorota Klepacki, Virag Sharma, Pavel V. Baranov, Andrew E. Firth, Tōnu Margus, Amira Kefi, Nora Vázquez-Laslop, Alexander S. Mankin. Retapamulin-Assisted Ribosome Profiling Reveals the Alternative Bacterial Proteome. Molecular Cell, 2019; DOI: 10.1016/j.molcel.2019.02.017

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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