Tuesday 30 June 2020

Holistic contamination control is central to revised EU GMP Annex 1

The main focal points from the 2020 draft of EU GMP Annex 1 (titled “Manufacture of Sterile Products”) signal to sterile products manufacturers a shift in regulatory thinking towards environmental controls rather than an over-reliance upon monitoring; with risk-based scientific thinking; and looking at contamination control holistically. The main themes are:

  • The expectation for each facility to have in place a formal, holistic contamination control strategy, focused on minimizing contamination control with respect to sterile manufacturing.
  • Additional requirements for cleanroom classification (beyond ISO 14644 requirements).
  • A major focus on risk-based approaches.
  • Recommendations for the wider use of barrier technology.
  • A strong focus on personnel controls, such as gowning, and training.

In relation to this, Tim Sandle has written an article. The reference is:

Sandle, T. (2020) 2020 Annex 1 Draft: Holistic Changes, Cleanroom Technology, 28 (5): 25-27

This article looks into some of the likely changes that will impact sterile products manufacturers, which can help organisations to stay ahead of the regulatory curve.

For details, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday 29 June 2020

COVID-19 and dental practice

Nobody could fail to miss the media coverage about novel coronavirus COVID-19, with daily and sometimes hourly updates about the ‘killer virus’. What exactly does it mean for dental practices in the UK?

In relation to this, Tim Sandle has written an article. Here is an extract:

"As coronaviruses have a lipid envelope, a wide range of disinfectants are effective. Human coronaviruses can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. A virucidal, ethanol-based disinfector/cleaner such as mikrozid liquid could play a useful role in the cleaning and disinfection of hard surfaces, particularly as it is effective against enveloped viruses within one minute."

The reference is:

Sandle, T. (2020) COVID-19 and dental practice, Dental Nursing, April 2020, pp2-3: https://www.magonlinelibrary.com/doi/full/10.12968/denn.2020.16.4.194

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday 28 June 2020

Presence of microbial DNA in blood may indicate signs of cancer

A new study indicates that looking for signs of certain microbial DNA in a patient's blood may be tell-tale sign of cancer. The discovery could help to advance cancer detection.

The new technique, which comes from the University of California - San Diego, works on the basis of a straightforward blood draw. When the blood is analyzed, the presence of microbial DNA could reveal whether the patient has cancer and then which type of cancer. The technique has produced accurate results, even for detecting signs of cancer at the early stages.
The basis of the technique came from an earlier study where it was shown that microorganisms invaded a majority of pancreatic cancers. In addition, certain types of microbes were found to be able to break down chemotherapy drugs. This led to the idea that examining a patient's microbiome could play a role in cancer detection.
This represented a shift in thinking, according to one of the scientists involved, Professor Rob Knight, who says: "Almost all previous cancer research efforts have assumed tumors are sterile environments, and ignored the complex interplay human cancer cells may have with the bacteria, viruses and other microbes that live in and on our bodies."
To develop the technique, the researchers examined 18,116 tumor samples, drawn from 10,481 patients. The patients had 33 different cancer types. By using a computer model, the analysis of the data revealed a series of distinct microbial signatures associated with specific cancer types.
For example, there was a connection between the bacterium Fusobacterium species and gastrointestinal cancers. The anaerobic Gram-negative organism has previously been linked with skin ulcers. As a second example, the researchers found an association between Faecalibacterium species and colon cancer. This Gram-positive anaerobe has previously been linked with Crohn's disease.
Such data is now being used to develop machine learning algorithms and with this the potential for a new, rapid cancer detection technology based on liquid biopsies.
The research has been published in the science journal Nature. The peer-reviewed study is titled: "Microbiome analyses of blood and tissues suggest cancer diagnostic approach."

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday 27 June 2020

Artificial intelligence finds new antibiotic

Technologists, working with microbiologists, have made a significant breakthrough in the hunt for new antimicrobials. By using artificial intelligence, a new candidate antibiotic has been identified.

The discovery was made using a machine-learning algorithm. This technology enabled scientists to discover a powerful new antibiotic compound.

The importance of the antibiotic has been shown through various tests, where the chemical was challenged against several disease-causing bacteria. Among the microbial cohort were some organisms previously identified to be resistant to mot antibiotics. Further studies were undertaken using mice, yielding similarly successful results.

READ MORE: Genetic testing can identify antibiotic resistance

The reason why there is strong scientific interest in finding new antibiotics is due to the phenomenon of antimicrobial resistance. This is a significant global health issue since the pace at which bacteria are becoming resistant to common antibiotic treatments is increasing. This means that infections that were once easy to treat are no longer certain of being tackled through existing medications. The consequence is that routine operations or transplants now present additional risks.

With the new discovery from MIT, the algorithm processed millions of chemical compounds, processing this vast data set in just a few days. This approach also avoided the necessity of running thousands of experiments; only those compounds selected by the machine learning program as having strong potential need be tested.

The use of computer models for drug screening and other applications is captured by the term “in silico.”

According to lead researcher Professor James Collins: “Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.”

He molecule selected has been named halicin (with a reference to the computer in 2001: A Space Odyssey). The drug was shown to be effective against Escherichia coli, as part of the tests. Further bacterial killing effects were demonstrated using other organisms of concern, such as Clostridium difficile, Acinetobacter baumannii, and Mycobacterium tuberculosis.

The bacterial killing properties of halicin arise from the compound’s ability to disrupt the electrochemical gradient across bacterial cell membranes, which triggers cell death.

ALSO READ: Antibiotic use may lead to heart problems

The research has been published in the journal Cell. The research paper is titled “A Deep Learning Approach to Antibiotic Discovery.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday 26 June 2020

Life Science Blogs To Follow

From BioPharma Trends:

"We have decided to summarize a list of niche blogs, mostly personal, run by the Life Science professionals - scientists, business leaders. Such blogs often provide personalized insights into certain areas of drug discovery, biotech, and business, which are not properly covered by the mainstream media, or covered in very general strokes. Reading blogs is a great way to explore nuances of the industry -- through the prism of personal opinions and experiences of the authors."

I'm pleased that this website - Pharmaceutical Microbiology resources - is featured in the list:

Pharmaceutical Microbiology

The site was created by Dr. Tim Sandle in 2009 to discuss pharmaceutical microbiology and healthcare. The posts are published every day. There is a lot of interesting information regarding microbes, bacteria, and disinfection, laboratory techniques, vaccines, antibiotics, and more. Sometimes, Dr. Sandle creates videos, where he explains different topics, including the latest series related to the COVID_19 pandemic.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday 25 June 2020

Additional safety protections relating to COVID-19 for faecal microbiota transplant (FMT) products

The Australian TGA has issued a document titled “Additional safety protections relating to COVID-19 for faecal microbiota transplant (FMT) products.”

The Therapeutic Goods Administration (TGA) is providing advice on safety protections to faecal microbiota transplant (FMT) providers since there is the potential to transmit the SARS-CoV-2 virus via FMT through shedding in stool.

FMT products comprise, contain, or are derived from donated human stool and are introduced into a recipient person for a therapeutic use. Human stool is collected from a screened donor by defaecation. This stool is then processed into an FMT product and provided to the recipient via enema, colonoscopy, nasoenteric tube, or orally (e.g. capsules).

This advice follows a recent safety alert from the US FDA that highlighted the additional safety precautions that should be in place for COVID-19 disease screening of potential stool donors for FMT products in order to prevent the spread of the SARS-CoV-2 virus.

See: https://www.tga.gov.au/alert/additional-safety-protections-relating-covid-19-faecal-microbiota-transplant-fmt-products

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday 24 June 2020

Compilation of QRD decisions on stylistic matters in product information

The European Medicines Agency has issued a compilation of ‘stylistic matters in product information’.

The document can be found here: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/compilation-quality-review-documents-decisions-stylistic-matters-product-information_en.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday 23 June 2020

Advanced therapy medicinal products: Overview

The European Medicines Agency has issued guidance on Advanced therapy medicinal products. Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues or cells. They offer ground-breaking new opportunities for the treatment of disease and injury.

ATMPs can be classified into three main types:

gene therapy medicines: these contain genes that lead to a therapeutic, prophylactic or diagnostic effect. They work by inserting 'recombinant' genes into the body, usually to treat a variety of diseases, including genetic disorders, cancer or long-term diseases. A recombinant gene is a stretch of DNA that is created in the laboratory, bringing together DNA from different sources; somatic-cell therapy medicines: these contain cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential functions in the body. They can be used to cure, diagnose or prevent diseases; tissue-engineered medicines: these contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue.

In addition, some ATMPs may contain one or more medical devices as an integral part of the medicine, which are referred to as combined ATMPs. An example of this is cells embedded in a biodegradable matrix or scaffold.

See: https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medicinal-products-overview

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday 22 June 2020

MHRA: Feedback from GMP inspections

To assist pharmaceutical manufacturers and distributors to understand the areas where good manufacturing practice (GMP) inspectors have found compliance problems during GMP inspections in the UK and overseas, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) GMP Inspectorate has issued data, during October 2019, relating to common deficiencies from previous GMP inspections conducted during 2018.

While the anonymised raw data provided by the GMP Inspectorate is of general interest, additional analysis is required to draw meaningful inferences. In this article, the data has been reviewed and presented, in order to obtain an overview of key trends.

These trends have bene captured in an article, written by Tim Sandle for GMP Review. The reference is:

Sandle, T. (2019) MHRA: Feedback from GMP inspections, GMP Review, 18 (3): 8-14

For further details, please contact Tim Sandle.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday 21 June 2020

Detecting anti-virus antibody in 20 minutes

Researchers have succeeded in detecting anti-avian influenza virus antibody in blood serum within 20 minutes, using a portable analyzer they have developed to conduct rapid on-site bio tests. If a suitable reagent is developed, this technology could be used to detect antibodies against SARS-CoV-2, the causative virus of COVID-19.

Avian influenza is a poultry disease caused by influenza A virus infection. Rapid initial response for a suspected infection and continuous surveillance are essential to mitigate the damage from highly pathogenic, transmittable pathogens such as avian influenza viruses.
Generally, the polymerase chain reaction (PCR) method is used to detect the viral genome, but its complicated procedure requires a considerable amount of time. Another method involves detecting antibodies produced in the body in reaction to virus infection. However, widely used antibody detection methods can be inaccurate because the antibodies' existence is generally determined by eyesight.

Researchers have developed a new method and analyzer capable of rapid, facile and selective detection of antibodies. The method is based on conventional fluorescence polarization immunoassay (FPIA) but applies a different measurement mechanism to make the analyzer much smaller and portable. The analyzer weighs only 5.5 kilograms.

The combined use of liquid crystal molecules, an image sensor and the microfluidic device makes it possible to simultaneously examine multiple samples and reduces the volume of each sample required. Liquid crystal molecules are capable of controlling the polarization direction of fluorescent light, while the microfluidic device has a number of microchannels as a measurement vessel.

The group also developed a reagent to detect anti-H5 avian influenza virus antibody, a fluorescein-labeled protein that binds only with the antibody. The reagent was made by reproducing hemagglutinin (HA) protein fragments, which are expressed on the surface of H5 avian influenza virus, through gene recombination and by labeling fluorescent molecules to the fragments.

Keine Nishiyama, Yohei Takeda, Masatoshi Maeki, Akihiko Ishida, Hirofumi Tani, Koji Shigemura, Akihide Hibara, Yutaka Yonezawa, Kunitoshi Imai, Haruko Ogawa, Manabu Tokeshi. Rapid detection of anti-H5 avian influenza virus antibody by fluorescence polarization immunoassay using a portable fluorescence polarization analyzer. Sensors and Actuators B: Chemical, 2020; 316: 128160 DOI: 10.1016/j.snb.2020.128160

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday 20 June 2020

Microbial cyborgs: Bacteria supplying power

One day "microbial cyborgs" might be used in fuel cells, biosensors, or bioreactors. Scientists of Karlsruhe Institute of Technology (KIT) have created the necessary prerequisite by developing a programmable, biohybrid system consisting of a nanocomposite and the Shewanella oneidensis bacterium that produces electrons. The material serves as a scaffold for the bacteria and, at the same time, conducts the microbially produced current.

The bacterium Shewanella oneidensis belongs to the so-called exoelectrogenic bacteria. These bacteria can produce electrons in the metabolic process and transport them to the cell's exterior. However, use of this type of electricity has always been limited by the restricted interaction of organisms and electrode. Contrary to conventional batteries, the material of this "organic battery" does not only have to conduct electrons to an electrode, but also to optimally connect as many bacteria as possible to this electrode. So far, conductive materials in which bacteria can be embedded have been inefficient or it has been impossible to control the electric current.

Researchers have succeeded in developing a nanocomposite that supports the growth of exoelectrogenic bacteria and, at the same time, conducts current in a controlled way. "We produced a porous hydrogel that consists of carbon nanotubes and silica nanoparticles interwoven by DNA strands," Niemeyer says. Then, the group added the bacterium Shewanella oneidensis and a liquid nutrient medium to the scaffold. And this combination of materials and microbes worked. "Cultivation of Shewanella oneidensis in conductive materials demonstrates that exoelectrogenic bacteria settle on the scaffold, while other bacteria, such as Escherichia coli, remain on the surface of the matrix," microbiologist Professor Johannes Gescher explains. In addition, the team proved that electron flow increased with an increasing number of bacterial cells settling on the conductive, synthetic matrix. This biohybrid composite remained stable for several days and exhibited electrochemical activity, which confirms that the composite can efficiently conduct electrons produced by the bacteria to an electrode.

Such a system does not only have to be conductive, it also must be able to control the process. This was achieved in the experiment: To switch off the current, the researchers added an enzyme that cuts the DNA strands, as a result of which the composite is decomposed.


Yong Hu, David Rehnlund, Edina Klein, Johannes Gescher, Christof M. Niemeyer. Cultivation of Exoelectrogenic Bacteria in Conductive DNA Nanocomposite Hydrogels Yields a Programmable Biohybrid Materials System. ACS Applied Materials & Interfaces, 2020; 12 (13): 14806 DOI: 10.1021/acsami.9b22116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday 19 June 2020

Terrestrial bacteria can grow on nutrients from space

For this study, four non-fastidious environment-derived bacterial species with pathogenic features were selected, including Klebsiella pneumoniae and Pseudomonas aeruginosa. A minimal 'diet' based on nitrogen, phosphorus, sulphur, iron and water to which carbohydrates found in carbonaceous meteorites were added was made to determine whether extraterrestrial survival and growth were possible. The four bacterial species were shown to survive and multiply on this minimal 'diet'.

In follow-up experiments, the team of researchers observed that the adaptation of bacteria, especially in the case of K. pneumoniae, caused changes in the cell membrane -- the shell of the cell -- as a result of which the immune system reacted more strongly to the bacteria. In short, the bacteria become more immunogenic. Research in cell culture, but also in mice, showed that the bacteria survive on extra-terrestrial nutrients and become less virulent as a result of this necessary adaptation. At the same time, this research shows that bacteria can survive under these conditions, which means that the risk of infection among space travellers remains, precisely because -- as other researchers have shown -- a space journey has negative effects on the functioning of the immune system, making astronauts more susceptible to infections.


Jorge Domínguez-Andrés, Marc Eleveld, Georgios Renieris, Thomas J. Boltje, Rob J. Mesman, Laura van Niftrik, Sam J. Moons, Petra Rettberg, Jos W.M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Huub J.M. Op den Camp, Marien I. de Jonge, Mihai G. Netea. Growth on Carbohydrates from Carbonaceous Meteorites Alters the Immunogenicity of Environment-Derived Bacterial Pathogens. Astrobiology, 2020; DOI: 10.1089/ast.2019.2173

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday 18 June 2020

Evolution of coronavirus SARS-CoV-2

A team of scientists studying the origin of SARS-CoV-2, the virus that has caused the COVID-19 pandemic, found that it was especially well-suited to jump from animals to humans by shapeshifting as it gained the ability to infect human cells.

Conducting a genetic analysis, researchers from Duke University, Los Alamos National Laboratory, the University of Texas at El Paso and New York University confirmed that the closest relative of the virus was a coronavirus that infects bats. But that virus's ability to infect humans was gained through exchanging a critical gene fragment from a coronavirus that infects a scaly mammal called a pangolin, which made it possible for the virus to infect humans.

The researchers report that this jump from species-to-species was the result of the virus's ability to bind to host cells through alterations in its genetic material. By analogy, it is as if the virus retooled the key that enables it to unlock a host cell's door -- in this case a human cell. In the case of SARS-CoV-2, the "key" is a spike protein found on the surface of the virus. Coronaviruses use this protein to attach to cells and infect them.

Very much like the original SARS that jumped from bats to civets, or MERS that went from bats to dromedary camels, and then to humans, the progenitor of this pandemic coronavirus underwent evolutionary changes in its genetic material that enabled it to eventually infect humans.

The researchers said tracing the virus's evolutionary pathway will help deter future pandemics arising from the virus and possibly guide vaccine research. The researchers found that typical pangolin coronaviruses are too different from SARS-CoV-2 for them to have directly caused the human pandemic.


Xiaojun Li, Elena E. Giorgi, Manukumar Honnayakanahalli Marichannegowda, Brian Foley, Chuan Xiao, Xiang-Peng Kong, Yue Chen, S. Gnanakaran, Bette Korber, Feng Gao. Emergence of SARS-CoV-2 through recombination and strong purifying selection. Science Advances, May 29, 2020: eabb9153 DOI: 10.1126/sciadv.abb9153

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday 17 June 2020

How bacteria purge toxic metals

In E. coli bacterium, the inner membrane sensor protein CusS mobilizes from a clustered form upon sensing copper ions in the environment. CusS recruits the transcription regulator protein CusR and then breaks down ATP to phosphorylate CusR, which then proceeds to activate gene expression to help the cell defend against the toxic copper ions.

Cornell researchers combined genetic engineering, single-molecule tracking and protein quantitation to get a closer look at this mechanism and understand how it functions. The knowledge could lead to the development of more effective antibacterial treatments.

The bacteria's resistance is actually a tag-team operation, with two proteins working together inside the cell. One protein (CusS), in the inner membrane, senses the presence of the chemical or metal and sends a signal to a regulator protein (CusR) in the cytosol, or intercellular fluid. The regulator protein binds to DNA and activates a gene that generates transport proteins, which purge the toxin from the cell.

Microbiologists analyze these functions by using biochemical assays that remove the protein from the cell. However, that process prevents the scientists from observing the proteins in their native environment, and certain details, such as the spatial arrangement between proteins, have remained murky.

For a deeper analysis, researchers used single-cell imaging, whereby they tagged individual proteins in living E. coli with a fluorescent signal and imaged the proteins one at a time, tracking their motions. The procedure yielded millions of images and, ultimately, a finely detailed, qualitative map of the proteins' movement.


Bing Fu, Kushal Sengupta, Lauren A. Genova, Ace George Santiago, Won Jung, Łukasz Krzemiński, Udit Kumar Chakraborty, Wenyao Zhang, Peng Chen. Metal-induced sensor mobilization turns on affinity to activate regulator for metal detoxification in live bacteria. Proceedings of the National Academy of Sciences, 2020; 201919816 DOI: 10.1073/pnas.1919816117

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday 16 June 2020

Efficient biosolar cells modelled on nature

Potential sources of renewable energy include protein complexes that are responsible for photosynthesis. However, their efficiency in technical applications still leaves much to be desired. For example, they cannot convert green light into energy. A research team has successfully closed this so-called green gap by combining a photosynthesis protein complex with a light-collecting protein from cyanobacteria.

Biosolar cells are an innovative concept for converting sunlight into electrical energy. They are manufactured using biological components from nature. At their core are so-called photosystems: large protein complexes that are responsible for energy conversion in plants, algae and cyanobacteria. Photosystem II, PSII for short, plays a central role in the process, because it can use water as an electron source for the generation of electricity.

The researchers stabilised these super complexes using short-chain chemical crosslinkers that permanently fix the proteins at a very short distance from each other. In the next step, they inserted them into appropriate electrode structure.

This design enabled the researchers to use twice as many photons within the green gap, compared to a system without any light collection complexes.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday 15 June 2020

Endotoxin control in depyrogenation tunnels

Understanding the way glassware is depyrogenated and how high concentrations of endotoxin can be used to assess how well depyrogenation tunnels are functioning is key to quality control.

In a new article, Tim Sandle explains:

Sandle, T. (2020) Endotoxin control in depyrogenation tunnels, Cleanroom Technology, February 2020. At: https://www.cleanroomtechnology.com/news/article_page/Endotoxin_control_in_depyrogenation_tunnels/162489

Here is an extract:

“The regulatory standard for validation of an endotoxin inactivation (depyrogenation) process is that it should be capable of reducing an endotoxin challenge through 3 log10 reduction. To ensure this limit works, it is required to clean materials before dry heat depyrogenation with WFI. Otherwise, at least in theory, you could have an item contaminated with 10,000 endotoxin units (EU) entering a validated endotoxin inactivation process and still emerging with 10 EU intact and ready to contaminate your product.

Dry heat depyrogenation is a complex process and is still poorly understood with contradictory research data. The phenomenon that complicates the picture is that inactivation may approximate to Second Order chemical kinetics with a high initial rate of inactivation, then tail off to nothing. In practice, this means that at any particular depyrogenating temperature you will get some degree of inactivation in some period of time or other, but beyond that point, you will get no further inactivation by holding the material at that temperature.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday 14 June 2020

Observing a continuous pathway to building blocks of life

A new study conducted by scientists at the Institute for Advanced Study, the Earth-Life Science Institute (ELSI), and the University of New South Wales marks an important step forward in the effort to understand the chemical origins of life. The findings of this study demonstrate how "continuous reaction networks" are capable of producing RNA precursors and possibly ultimately RNA itself -- a critical bridge to life.

While many of the mechanisms that propagate life are well understood, the transition from a prebiotic Earth to the era of biology remains shrouded in mystery. Previous experiments have demonstrated that simple organic compounds can be produced from the reactions of chemicals understood to exist in the primitive Earth environment. However, many of these experiments relied on coordinated experimenter interventions. This study goes further by employing a model that is minimally manipulated to most accurately simulate a natural environment.

To conduct this work, the team exposed a mixture of very simple small molecules -- common table salt, ammonia, phosphate, and hydrogen cyanide -- to a high energy gamma radiation source. These conditions simulate radioactive environments made possible by naturally occurring radioactive minerals, which were likely much more prevalent on early Earth. The team also allowed the reactions to intermittently dry out, simulating evaporation in shallow puddles and beaches. These experiments returned a variety of compounds that may have been important for the origins of life, including precursors to amino acids and other small compounds known to be useful for producing RNA.

The authors use the term "continuous reaction network" to describe an environment in which intermediates are not purified, side products are not removed, and no new reagents are added after the initial starting materials. In other words, the synthesis of molecules occurs in a dynamic environment in which widely varied compounds are continuously being formed and destroyed, and these products react with each other to form new compounds.

Future work will focus on mapping out reaction pathways for other chemical substances and testing whether further cycles of radiolysis followed by dry-down can generate higher order chemical products.


Ruiqin Yi, Quoc Phuong Tran, Sarfaraz Ali, Isao Yoda, Zachary R. Adam, H. James Cleaves, Albert C. Fahrenbach. A continuous reaction network that produces RNA precursors. Proceedings of the National Academy of Sciences, 2020; 201922139 DOI: 10.1073/pnas.1922139117

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday 13 June 2020

Developing a new weapon in the war against superbugs

Australian microbiologists have shown that a newly discovered natural antibiotic, teixobactin, could be effective in treating bacterial lung conditions such as tuberculosis and those commonly associated with COVID-19. 
Teixobactin was discovered in 2015 by a team led by Professor Kim Lewis at Northeastern University in Boston in 2015. His company is now developing it as a human therapeutic.
The new University of Melbourne research is the first to explain how teixobactin works in relation to the superbug Staphylococcus aureus -- also known as MRSA.
MRSA is among bacteria responsible for several difficult-to-treat infections in humans, particularly post-viral secondary bacterial infections such as COVID-19 chest infections and influenza.


Maytham Hussein, John A. Karas, Elena K. Schneider-Futschik, Fan Chen, James Swarbrick, Olivia K. A. Paulin, Daniel Hoyer, Mark Baker, Yan Zhu, Jian Li, Tony Velkov. The Killing Mechanism of Teixobactin against Methicillin-Resistant Staphylococcus aureus: an Untargeted Metabolomics Study. mSystems, 2020; 5 (3) DOI: 10.1128/mSystems.00077-20

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday 12 June 2020

Digital PCR: Novel approach for COVID-19 testing

Stilla Technologies, a leading French provider of pioneering solutions for high precision genetic analysis, is offering a new high-throughput and cost-effective testing approach for COVID-19 by combining its digital PCR technology with the group testing

method and publishes the largest comparative study to date for group testing of SARS-CoV-2.

"We continue our efforts in the fight against Covid-19 and are proud today to present an innovative approach that greatly increases the testing capacity and meets the highest quality standards. This digital PCR based group testing method has a diagnostic sensitivity superior or equal to the current standard - that is individual RT-PCR testing - for group sizes up to 16 samples. The main benefit of this method is that it reduces the amount of reagent required to test a population by about 80% while reducing costs by as much and increasing test capacities by up to 10 times", said Rémi Dangla, Co-founder and CEO of Stilla Technologies.

Currently, testing for SARS-CoV-2 infections is central to strategies deployed to contain the spread of the virus worldwide. Patients are diagnosed predominantly using virological tests based on a technology called real-time reverse transcription polymerase chain reaction (RT-PCR).

RT-PCR technique is reaching its limits as the demand for SARS-CoV-2 RT-PCR testing is increasing worldwide as more countries are impacted by COVID-19. Firstly, because testing individual samples using RT-PCR is not scalable. Indeed, testing facilities are facing a scarcity of reagents worldwide while the demand reaches millions of tests. In fact, laboratories experienced a severe shortage of reagents at the start of the pandemic and are still under tension today to stock up on supplies. Secondly, because the cost of testing is not scalable to the world population. Group testing or sample pooling has been proposed as a solution to expand testing capabilities.

Test positivity rate for COVID-19 testing after lock-down (and before a pandemic) is usually below 10%, often around 1%, which means that 99 tests out of 100 are expected to yield negative results.

Group tests are optimal in such a configuration of low positivity rate. In a group test, the samples of 8, 16 or 32 individuals are combined into a pooled sample. This pooled sample is then tested. If the test is negative, it means that all the individuals in the group are negative. If it is positive, it means that at least one individual is a carrier of SARS-CoV-2. It is then necessary to test every sample separately again to identify the carrier(s). With a test positivity rate of 1%, only 1 in 10 groups will be positive. The test savings are therefore substantial, around 80%. Additionally, this group testing approach multiplies the number of individuals tested for a given amount of reagents by a factor of 5.

However, a risk associated with group tests is their sensitivity, which is deemed to be lower for large groups (n> 4). This reduction in sensitivity means that there is an increased risk of not detecting certain carriers of the virus with pooled tests compared to individual tests. This is where Stilla Technologies' Crystal digital PCR™ technology comes in. Digital PCR is known to be more sensitive than standard RT-PCR technology. Recent studies have verified it for the detection of SARS-CoV-2. Thus, the association of digital PCR with the group testing method would address the main problem of sensitivity.

This is what the study released today confirms. This study, conducted by the Virology Department of Bichat Hospital (AP-HP) in collaboration with CREST (Ecole Polytechnique) and Stilla Technologies is the largest comparative study carried out to date, systematically comparing group tests of SARS- CoV-2 to individual reference tests. It is also the first study to evaluate group tests combined with digital PCR.

Out of 448 samples tested, 26 and 25 tested positive by digital PCR group test, for group sizes of 8 and 16 samples. Against 25 tested positive with individual reference tests in RT-PCR. Thus, the study demonstrates a similar sensitivity to better for group tests by digital PCR, compared to individual tests by RT-PCR.

In conclusion, this new approach of group testing by digital PCR appears to have a diagnostic sensitivity "similar to better" compared to current tests in individual RT-PCR. However, this method makes it possible to reduce the amount of reagent required by up to 80% while reducing costs as well and increasing the capacity of testing by digital PCR up to 10 times. In conclusion, these are substantial advantages that make this approach a precious weapon to deploy in the fight against the pandemic.

Posted by Dr. Tim Sandle, 
Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday 11 June 2020

How your business can become more resilient during coronavirus

Many businesses have faced widespread disruption during the COVID-19 era, with many companies being forced to diversify or to advance digital transformation plans. Phillipa Hurrell provides some advice for business leaders.

According to Hurrell, these issues are inevitable, it is how you as a business have the ability to bounce back from any setbacks you are faced with. However, by following these five steps Hurrell says that business owners can deal with complications and to promptly come up with innovative plans to move their business forward.
Phillipa Hurrell is the Performance Coach of Hurrell Associates and The Courage Club. In conversation with Digital Journal, Phillipa looks into five ways focusing on increasing business owners' resilience and helping businesses grow, during these uncertain times.


Have you accepted the impact COVID-19 has had on your business and life? Acceptance is a simple concept; it means we understand that what has happened cannot be changed. Acceptance is important as it allows you to open up to new possibilities. You no longer put energy into fighting or questioning it. Instead, you put your energy into moving forward.

First, we must acknowledge what has happened. This cannot be rushed, it might take you a few hours, days or even weeks. We are human beings and, by our nature, emotional. It’s important at this phase to acknowledge the emotions you are feeling and be honest about them.

Write down how you are feeling, tell a trusted friend or family member. Sharing emotions is like a release valve that lets the pressure out. It’s one of the first steps in solving a problem. Emotions do not make you weak, they make you human and it’s a question of what we do about them and how long we choose to sit on them. Just be aware that the longer you choose to sit on the negative emotions, the more ingrained they become.

Ask yourself questions that can help you move out of this phase such as: is my current response appropriate and effective? Will it help my business? What can the business learn from this situation? What positives can I find in this situation?

Radical responsibility

Are you being 100% accountable for what you do next? When bad things happen in our lives the invitation is there to blame others and become bitter for our bad luck. It might be tempting to tell all that will listen of your unique bad luck in a certain situation. This stance is called learned helplessness and involves telling a story so often that you cannot do anything to help yourself but believe it.

The alternative perspective is to take full-blown responsibility for what you do next and what you choose to learn, what opportunities you choose to see and whether you choose to do something useful and positive. Our brains are amazing machines; they do what we instruct them to. Are you instructing your brain to find the possibilities and ideas to move you forward?

Positive mindset

Are you choosing a mindset that is going to help you? Our mindset is a way of thinking, a set of beliefs that govern how we feel and how we choose to react to situations. Your mindset has a huge impact on the course of your life. Is yours helping or hindering you? There are two particular mindsets that will help boost your resilience:

Focus on not merely surviving but thriving

Our lives are built on change; just think about how much change you have already successfully navigated in your life. From school to technology, moving house to changes in your family, friendships groups and illness and bereavement. You have so many examples of where you have been resilient and come through the change stronger.

Having a mindset fixed on your ability to not just survive during change but thrive, will help. Some businesses and people will come out of the current pandemic stronger, more customer-focused, streamlined and confident – so why shouldn’t you?


The second mindset is one of gratitude. If you are grateful for what you have, you will end up with more of it. Choosing every day to fix your mindset on what you have and what you are grateful for changes how your brain is wired and you very quickly start to notice all the amazing things that you have access to.

Focus on all that you have rather than what you lack. Spending one minute everyday writing down three things you are grateful for will help you think positively during these uncertain and worrying times.


Do you believe you can get through this? One of the biggest studies on the impact of self-belief was carried out by Albert Bandura and he found that a person’s self-belief is a significantly better predictor of future success than the actual results people have produced in the past.

So, what you have done in the past does not matter as much as how much you believe in yourself right now!

A good place to start in building self-belief is to notice all of the brilliant qualities you already possess. You are hugely valuable, you are unique, you are what has created your business and no one else has your specific set of skills, knowledge and capabilities.

Some people believe how valuable they are is based on their net worth or how big their business is and how many customers they have. Your value is ‘you’, you created all of those things. We forget where our success comes from and that we are capable of creating so much more.

Positive goals

Have you got clear, defined and inspiring goals? Goal setting is a simple way to help you feel like you are back in control.

Step one: Start by visualising what you want to happen.

Think about one year ahead (be positive and realistic) and allow your mind to create a vision of your future. How will you be feeling, what have you learned, how are you serving your customers? Having a clear purpose is really important for remaining resilient. Are your goals compelling? What could make these goals a 10 out of 10 for you?

Step two: Write down all the ways you could start to make these goals happen and all the options available to you.

Stretch your thinking beyond what you would normally consider. What could you do? What have others done in the past? The more you stretch your thinking, the better you will feel. It reinforces how many ways there are to look at any given situation or solve any problem, which stops you feeling stuck.

Step three: Choose the best options and start to research steps to move this forward.

Imagine if you took positive action every day to make these goals happen. Where would you be in six months? Information can empower you and it can stop you feeling stuck. A person with a smartphone now has more information, insight, and data at their fingertips than world leaders and the biggest companies did 15 years ago.

There is so much research and advice online to help you understand and act on the current climate. From what the experts believe the impacts will be (McKinsey & Company’s website has some interesting reading) to data on the changes in consumer habits in economies that are coming out of lockdown ahead of us.

Research how your specific industry is adapting and how other businesses are changing. What can you learn from the last recession and the companies that came out of that stronger? What can you learn about innovation, strategy, and helping your business pivot? And what can you learn from consumer forums? It’s about what proactive research you can do to gather insight that will help. Research, insight, and data helps but is all pointless if you don’t take action and learn.

And lastly, what we practice, we become, and most people have spent their lives telling themselves they can’t go after what they want, holding themselves back and playing it safe. Maybe it’s time to really think about what you want and have the courage to go after it!

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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