Sunday, 15 September 2019

How microorganisms protect themselves against free radicals

There are numerous different scenarios in which microorganisms are exposed to highly reactive molecules known as free radicals. These molecules are capable of damaging important cell components and may be generated during normal cell metabolism or in response to environmental factors. Free radicals play a significant role in antibiotic effectiveness, the development of diseases and the normal functioning of the human immune system.

A team of researchers from Charité -- Universitätsmedizin Berlin has discovered a previously unknown mechanism which enables microorganisms to protect themselves against free radicals.

The term free oxygen radicals refers to highly reactive oxygen molecules which are capable of damaging a range of important cell structures such as proteins, DNA and cell membranes. While free radicals represent a destructive force, it is one which the human body has learned to exploit. Some cells of the human immune system produce free radicals as part of their fight against invading microorganisms. Metabolic processes also result in the production of free radicals when microbial cells come into contact with antibiotics. This is an important factor behind their activity.

Microorganisms have developed various mechanisms to intercept and neutralize these highly reactive molecules in order to deflect an immune system attack. An international team of researchers has now been able to show that microorganisms also have another, previously unknown defensive strategy at their disposal. Compared with previously documented mechanisms, this strategy could prove particularly effective.

The researchers started their investigations using baker's yeast as the model organism, observing that yeast cells accumulate vast quantities of lysine, a building block used in the production of yeast proteins. After being absorbed from the environment, lysine was stored at levels 70 to 100 times higher than those necessary for normal growth. Using mathematical modeling and genetic analysis to determine the purpose of this 'lysine harvest', the researchers discovered that yeast cells use the accumulated lysine to alter their own metabolism. One of the consequences of this reconfiguration was the production of extraordinary amounts of glutathione, one of the most important radical scavenging molecules found in living organisms. Following lysine harvest, yeast cells were shown to have significantly increased resistance against free radicals. This enabled them to break down quantities of free radicals which would normally have resulted in cell death. The researchers demonstrated that this resistance mechanism is used not only by different types of yeast, but also by bacteria.


Viridiana Olin-Sandoval, Jason Shu Lim Yu, Leonor Miller-Fleming, Mohammad Tauqeer Alam, Stephan Kamrad, Clara Correia-Melo, Robert Haas, Joanna Segal, David Alejandro Peña Navarro, Lucia Herrera-Dominguez, Oscar Méndez-Lucio, Jakob Vowinckel, Michael Mülleder, Markus Ralser. Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism. Nature, 2019; DOI: 10.1038/s41586-019-1442-6

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 14 September 2019

Quarter of the world's population at risk of developing tuberculosis

A new study from Aarhus University Hospital and Aarhus University, Denmark, has shown that probably 1 in 4 people in the world carry the tuberculosis bacterium in the body. The disease tuberculosis is caused by the bacterium Mycobacterium Tuberculosis, which affects more than 10 million people every year, and kills up to 2 million, making it the most deadly of the infectious diseases.

In addition, many are infected with the tuberculosis bacterium without having active disease, which is called latent tuberculosis. This number has so far been estimated on the basis of assumptions on how many a patient with active tuberculosis may infect, but there has not been an empirical basis for these assumptions.

Now, researchers from Denmark and Sweden have used a new method to describe the occurrence of latent tuberculosis infection. The researchers have reviewed 88 scientific studies from 36 different countries, and on the basis of this epidemiological evidence they have estimated a prevalence also in those countries where no studies are available, additionally they have calculated the approximate total global prevalence.

The study emphasizes that it will be extremely difficult to reach the goal of eliminating tuberculosis by 2035, which is the aim of the WHO. At any rate, the objective cannot be achieved without treating the large incidence of latent tuberculosis, since all infected people are at risk of developing active tuberculosis disease later in life, says Christian Wejse, an infectious disease specialist at Aarhus University Hospital and Associate Professor at Aarhus University, Denmark.

It has previously been estimated that somewhere between one-third and one-fourth have latent tuberculosis, but the new study, which is based on tests from 351,811 individuals, indicates that it is between one-fifth and one-fourth, depending on the test method used. The study thus documents a significant occurrence of tuberculosis infection in the world today, albeit slightly less than previously thought.


Adam Cohen, Victor Dahl Mathiasen, Thomas Schön, Christian Wejse. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. European Respiratory Journal, 2019; 1900655 DOI: 10.1183/13993003.00655-2019

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 13 September 2019

Children might be naturally immunized after C. difficile colonization

Exposure to C. difficile in infancy produces an immune response that might protect against this gastrointestinal infection later in childhood.

Researchers found that infants who were naturally exposed to C. difficile in the environment and became colonized with the bacteria had antibodies in their blood. Analyses using a state-of-the-art assay revealed that these antibodies neutralized toxins that cause C. difficile infection, preventing harmful effects to cells exposed to these toxins. This suggests that a natural immunization occurs, although future studies will need to determine if it would prevent illness years later after another C. difficile exposure.

C. difficile is a frequent cause of community- and healthcare-associated infection in adults and children. While roughly half of all infants get exposed, they normally do not get sick from these bacteria. Older children and adults usually get diarrhea that needs to be treated by antibiotics. A more severe form of the infection may cause inflammation of the colon that requires surgery and could be fatal. Children tend to have milder symptoms than adults. The pediatric incidence of C. difficile infection peaks in the 1-to-4-year age group and during teenage years.


Larry K Kociolek, Robyn O Espinosa, Dale N Gerding, Alan R Hauser, Egon A Ozer, Maria Budz, Aakash Balaji, Xinhua Chen, Robert R Tanz, Nazli Yalcinkaya, Margaret E Conner, Tor Savidge, Ciaran P Kelly. Natural Clostridioides difficile toxin immunization in colonized infants. Clinical Infectious Diseases, 2019; DOI: 10.1093/cid/ciz582

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 12 September 2019

How Should Analytical Balances Be Calibrated?

Weighing balances are an important part of the equipment used in analytical laboratories, even if the lab isn’t equipped with a wide range of analytical instruments. Weighing is involved in the preparation of sample solutions, reagents, precipitates, and more. At every stage of analysis, precise weight measurements are critical to getting accurate results.

A guest post by Kevin Hill.

Analytical balances are a highly sensitive type of weighing equipment, which can measure the mass of a substance to within 0.00001 grams. Such high precision may not be needed in every sector, but it’s often a basic requirement for pharmaceutical laboratory analysts when they’re weighing a sample.

The weighing accuracy of analytical balances is determined by measuring how close the actual weight of a sample is to the result displayed by the instrument. The process used to determine this accuracy is known as calibration.

Calibration Procedure for Analytical Balances

Here’s a step-by-step guide on how to calibrate an analytical balance:

1. Check whether there is a specific calibration procedure for the balance you’re testing. For certain laboratories, especially in the pharma industry, regulatory requirements include the calibration procedure that needs to be followed for each instrument.

2. If the analytical balance has a calibration sticker, check its expiry date. Out-of-date calibrations may require a more thorough testing than you can conduct, so call an expert to be sure that the balance will give accurate results during use.

3. Check the manufacturer’s documentation or the instrument’s calibration sticker to understand the recommended calibration frequency. Certain models of analytical balances require regular external calibration, while others only need it from time to time because they feature internal automatic calibration.

4. Make sure that no one has moved the instrument, or switched it off during the last hour. The accuracy of analytical balances is affected by these factors. Wait an hour after switching the instrument back on, and perform a thorough recalibration or call a professional if the balance has been moved.

5. Use the adjustable feet of the balance to raise one side higher or lower till the bubble on the spirit level is centered. If the instrument isn’t even, it will not deliver accurate results during calibration or use.

6. If the analytical balance has a door, open it and use a soft brush or dry cloth to clean the weighing surface. Make sure the balance is totally clean, since dust or particles on it may cause inaccuracies in measurement results.

7. After closing the door of the balance, press the “Tare” button and wait a few seconds for the reading to settle. Proceed to the next step after the reading from the balance shows zero.

8. Depending on the item types you weigh, choose standardized weights against which to calibrate the instrument. You can use one weight if it meets the requirements of your lab, or multiple weights across the capacity of the balance if you usually weigh a larger range. These weights should be traceable to international standards such as NIST.

9. Open the instrument’s door and gently place the first test weight on the center of the balance. Then, close the door and wait a few seconds for the balance to settle before recording and removing the test weight. Make sure you use tweezers or wear gloves while handling weights, since moisture and oil from your skin can affect the results.

10. Repeat the previous step for each of the test weights you’ve chosen. Check the device’s calibration guidelines or manual to confirm if any drift in measurements is within acceptable tolerance levels, before using the balance.

Author Bio: Kevin Hill heads the marketing efforts at Quality Scales Unlimited in Byron, CA. Besides his day job, he loves to write about the different types of scales and their importance in various industries. He also writes about how to care for and get optimized performance from different scales in different situations. He enjoys spending time with family and going on camping trips

Wednesday, 11 September 2019

Tenth edition of Ph Eur

Details of the tenth edition of the European Pharmacopeia have been published. The European Pharmacopoeia (Ph. Eur.) is a single reference work for the quality control of medicines. The official standards published within provide a scientific basis for quality control during the entire life cycle of a product.

The general chapters being updated are:

2.2.25. Absorption spectrophotometry, ultraviolet and visible
2.6.8. Pyrogens
2.6.33. Residual pertussis toxin
2.7.2. Microbiological assay of antibiotics
2.7.23. NumerationofCD34/CD45+cellsinhaematopoietic products
2.7.35. Immunonephelometry for vaccine component assay
2.8.25. High-performance thin-layer chromatography of herbal drugs and herbal drug preparations
2.9.1. Disintegration of tablets and capsules
2.9.20. Particulate contamination visible particles
3.1.13. Plastic additives
3.3.1. Materials for containers for human blood and blood components
3.3.2. Materials based on plasticised poly(vinyl chloride) for containers for human blood and blood components
3.3.3. Materials based on plasticised poly(vinyl chloride) for tubing used insets for the transfusion of blood and blood components
3.3.4. Sterile plastic containers for human blood and blood components
3.3.5. Empty sterile containers of plasticised poly(vinyl chloride) for human blood and blood components
3.3.6. Sterile containers of plasticised poly(vinyl chloride) for human blood containing anticoagulant solution
3.3.7. Sets for the transfusion of blood and blood components
3.3.8. Sterile single-use plastic syringes

The 10th edition of the Pharmacopoeia will contain 114 new and 683 revised texts, approximately 30% of the content is new or revised compared to Edition 9.0.

It contains 2 420 monographs, 374 general texts (including general monographs and methods of analysis) and around 2 780 descriptions of reagents.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 10 September 2019

Will your future computers be made using bacteria?

Future of computing?

In order to create new and more efficient computers, medical devices, and other advanced technologies, researchers are turning to nanomaterials: materials manipulated on the scale of atoms or molecules that exhibit unique properties.

Graphene -- a flake of carbon as thin as a single later of atoms -- is a revolutionary nanomaterial due to its ability to easily conduct electricity, as well as its extraordinary mechanical strength and flexibility. However, a major hurdle in adopting it for everyday applications is producing graphene at a large scale, while still retaining its amazing properties.

In a paper published in the journal ChemOpen, Anne S. Meyer, an associate professor of biology at the University of Rochester, and her colleagues at Delft University of Technology in the Netherlands, describe a way to overcome this barrier. The researchers outline their method to produce graphene materials using a novel technique: mixing oxidized graphite with bacteria. Their method is a more cost-efficient, time-saving, and environmentally friendly way of producing graphene materials versus those produced chemically, and could lead to the creation of innovative computer technologies and medical equipment.

Graphene is extracted from graphite, the material found in an ordinary pencil. At exactly one atom thick, graphene is the thinnest -- yet strongest -- two-dimensional material known to researchers. Scientists from the University of Manchester in the United Kingdom were awarded the 2010 Nobel Prize in Physics for their discovery of graphene; however, their method of using sticky tape to make graphene yielded only small amounts of the material.
"For real applications you need large amounts," Meyer says. "Producing these bulk amounts is challenging and typically results in graphene that is thicker and less pure. This is where our work came in."

In order to produce larger quantities of graphene materials, Meyer and her colleagues started with a vial of graphite. They exfoliated the graphite -- shedding the layers of material -- to produce graphene oxide (GO), which they then mixed with the bacteria Shewanella. They let the beaker of bacteria and precursor materials sit overnight, during which time the bacteria reduced the GO to a graphene material.

"Graphene oxide is easy to produce, but it is not very conductive due to all of the oxygen groups in it," Meyer says. "The bacteria remove most of the oxygen groups, which turns it into a conductive material."

While the bacterially-produced graphene material created in Meyer's lab is conductive, it is also thinner and more stable than graphene produced chemically. It can additionally be stored for longer periods of time, making it well suited for a variety of applications, including field-effect transistor (FET) biosensors and conducting ink. FET biosensors are devices that detect biological molecules and could be used to perform, for example, real-time glucose monitoring for diabetics.

"When biological molecules bind to the device, they change the conductance of the surface, sending a signal that the molecule is present," Meyer says. "To make a good FET biosensor you want a material that is highly conductive but can also be modified to bind to specific molecules." Graphene oxide that has been reduced is an ideal material because it is lightweight and very conductive, but it typically retains a small number of oxygen groups that can be used to bind to the molecules of interest.

The bacterially produced graphene material could also be the basis for conductive inks, which could, in turn, be used to make faster and more efficient computer keyboards, circuit boards, or small wires such as those used to defrost car windshields. Using conductive inks is an "easier, more economical way to produce electrical circuits, compared to traditional techniques," Meyer says. Conductive inks could also be used to produce electrical circuits on top of nontraditional materials like fabric or paper.

READ MORE: Technique identifies electricity-producing bacteria

"Our bacterially produced graphene material will lead to far better suitability for product development," Meyer says. "We were even able to develop a technique of 'bacterial lithography' to create graphene materials that were only conductive on one side, which can lead to the development of new, advanced nanocomposite materials."


Benjamin A. E. Lehner, Vera A. E. C. Janssen, Ewa M. Spiesz, Dominik Benz, Stan J. J. Brouns, Anne S. Meyer, Herre S. J. van der Zant. Creation of Conductive Graphene Materials by Bacterial Reduction Using Shewanella Oneidensis. ChemistryOpen, 2019; 8 (7): 888 DOI: 10.1002/open.201900186

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 9 September 2019

The answer is? FDA publishes final data integrity Q&A

Despite much discussion about the subject over the past 3 years, in particular, data integrity issues remain a common feature on 483 letters issued by the USA Food and Drug Administration (FDA) and data handling matters are also a focus of enforcement actions (as well as inspection findings from other regulatory agencies). It is perhaps for this reason that the FDA has issued a new guidance document entitled Data Integrity and Compliance with Drug cGMP: Questions and Answers – Guidance for Industry.

In relation to this topic, Tim Sandle has written an article for GMP Review:

This article reviews the new FDA data integrity guidance document and draws out some items of interest for the pharmaceutical and healthcare sectors. The aim here is not to overly repeat what is in the document (since the reader could and should be doing this for themselves), but to note the differences between the final document and the earlier draft and to draw out the key themes within the document.

The reference is:

Sandle, T. (2019) The answer is? FDA publishes final data integrity Q&A, GMP Review, 17 (4): 4-7

For a copy, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 8 September 2019

Immune responses to dengue virus in the skin

Dengue virus (DENV) causes infection in humans and current estimates place 40% of the world population at risk for contracting disease.

An article of interest:

There are four DENV serotypes that induce a febrile illness, which can develop into a severe and life-threatening disease in some cases, characterized primarily by vascular dysregulation. As a mosquito-borne infection, the skin is the initial site of DENV inoculation and also where primary host immune responses are initiated. This review discusses the early immune response to DENV in the skin by both infection target cells such as dendritic cells and by immune sentinels such as mast cells. We provide an overview of the mechanisms of immune sensing and functional immune responses that have been shown to aid clearance of DENV in vivo. Finally, we discuss factors that can influence the immune response to DENV in the skin, such as mosquito saliva, which is co-injected with virus during natural route infection, and pre-existing immunity to other DENV serotypes or to related flaviviruses.


Immune responses to dengue virus in the skin Abhay P. S. Rathore and  Ashley L. St. John


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 7 September 2019

Why does drug resistance readily evolve but vaccine resistance does not?

Why is drug resistance common and vaccine resistance rare? Drugs and vaccines both impose substantial pressure on pathogen populations to evolve resistance and indeed, drug resistance typically emerges soon after the introduction of a drug.

An article of interest:
But vaccine resistance has only rarely emerged. Using well-established principles of population genetics and evolutionary ecology, we argue that two key differences between vaccines and drugs explain why vaccines have so far proved more robust against evolution than drugs. First, vaccines tend to work prophylactically while drugs tend to work therapeutically. Second, vaccines tend to induce immune responses against multiple targets on a pathogen while drugs tend to target very few. Consequently, pathogen populations generate less variation for vaccine resistance than they do for drug resistance, and selection has fewer opportunities to act on that variation. When vaccine resistance has evolved, these generalities have been violated. With careful forethought, it may be possible to identify vaccines at risk of failure even before they are introduced.


Why does drug resistance readily evolve but vaccine resistance does not? David A. Kennedy and Andrew F. Read

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 6 September 2019

Producer of bovine colostrum to take on gut health microbiome

PanTheryx, a biotechnology company focused on addressing serious GI related health conditions, announced today that it has completed $50 million in new financing with Perceptive Advisors. Proceeds from the financing will be used to accelerate development of novel medical foods and biologics in the company’s pipeline as well as support expansion of its existing line of nutritionals, including its flagship product, DiaResQ.

“Many of the most debilitating diseases in the world are multifactorial, with challenges from pathogen exposure further confounded by immune dysregulation and imbalances within commensurate microbiota in the GI tract,” said Mark Braman, CEO of PanTheryx. “With this new backing from Perceptive, one of the leading healthcare investors, we have the resources to rapidly bring to market therapeutics that will greatly improve the standard of care and dramatically enhance the quality of life of patients suffering from GI conditions.”

PanTheryx’s pipeline includes novel candidates for addressing C. difficile infections, Crohn’s Disease, Ulcerative Colitis, and managing GI related side effects of cancer therapies. Rather than developing de novo molecules with a single target, the company’s candidates are being developed with bioactive backbones that contains multiple molecules with complementary mechanisms of action.

“PanTheryx’s approach of leveraging the immuno-therapeutic, anti-inflammatory and restorative fractions of bovine colostrum has the potential to revolutionize the way practitioners approach many of the difficult to treat GI conditions patients face today” said Sam Chawla, portfolio manager, Perceptive Advisors. “Partnering with PanTheryx at this exciting time in the company’s lifecycle will allow them to accelerate the development of truly innovative therapies that we believe will fill significant unmet needs for many patients worldwide.”

Armentum Partners acted as financial advisor to PanTheryx. The Perceptive transaction brings the total financing raised by PanTheryx to $170 million.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 5 September 2019

Best Foods that Fight Cold and Flu

When an individual is sick, they might feel it problematic to develop a hunger. Though it is significant to obtain suitable food and stay hydrated, particularly when feeling unwell. Cold is a common illness which is initiated by germs, and a regular adult can get cold more than one time in a year. 

A guest post by Emylee.

Though cold is not unsafe, it can leave the pretentious individual in uneasiness and annoyed. The feeling of cold is a terrible one. Lots of rest is required for handling a cold you'll be most relaxed in a warm, moist environment. It's also vital to stay hydrated by drinking loads of water and stop having caffeine and alcohol. This makes secretion flow more smoothly and starts with congestion. 

Indications of a common cold typically seem one to three days after contacting to a cold-causing virus. Signs and symptoms that could change from individual to individual are:

  • Runny or stuffy nose
  • Painful throat
  • Cough
  • Congestion
  • Minor body pains or a mild headache
  • Sneezing
  • Fever
  • Usually feeling unwell
  • Blocked nose
The following foods can help to ease congestion and irritation and lift the immune system.

1. Honey and warm water:

The use of lukewarm water with basil leaves and honey is the best remedy to cure a cold. It helps to calm the cough efficiently. It is the most beautiful natural cold remedies that are prevalent. In fact, as per the research, honey has been seemed to be as current as a natural cough suppressant element, dextromethorphan, in distinctive OTC doses. Because honey is less -expensive and widely available, it should be tried.

2. Bananas:

Bananas are filled with potassium and various other powerful nutrients like as fiber and vitamin B6; a banana is the best fruit when it comes to solidification your immune system. They contain loads of calcium as well, which helps your body fight contamination. Eat your bananas cut over whole-grain cereal and pair it with the germ-busting power.

3. Eggs:

Eggs are one of the simple remedies to cure a common cold. It contains protein and protein is essential to creating muscle and letting your body remain tough. Eggs are also useful in minerals and vitamins such as B6 and B12, which gives to a healthy immune system. Also, when you are unwell, your stomach possibly will not be able to take any task of digest any large meal. You will still require protein to preserve your strength, whether you are perfectly fit or you're sick.

4. Dark leafy greens and bell peppers:

When it comes to receiving more vitamin C, you might think of citrus bell peppers as well as dark leafy greens, which include spinach, kale, romaine lettuce, broccoli, and Brussels sprouts. They all have lots of Vitamin C, which can further make a cold or flu go away. On the other hand, red bell peppers have much more vitamin c and D similar to orange. It is suggested that having few of these vegetables uncooked, or dipped in some sauce for around additional protein, to make the most of nutritious content can help to increase the immune system.

5. Chicken Soup:

Chicken soup gives you warmth and comfort. It has been suggested as a natural cold and flu remedies for hundreds of years and is fast, easy, and inexpensive. It helps clear nasal congestion as well as thin mucus so you can better cough it up. Also, research shows it may have a mild anti-inflammatory effect than can help ease symptoms. Comparable to chicken soup, broths are excellent sources of hydration when you are sick.

6. Mushrooms:

Mushrooms have some form of immune-boosting antioxidants, such as potassium B vitamins, and fiber. Mushrooms are rich in a type of polysaccharide known as beta-glucan, which can "stimulate" the immune system and benefit in avoiding any toxicities.

7. Wild salmon

Wild salmon has loads of zinc, a nutrient that has been confirmed to assist with reducing common cold symptoms. If you want your family, particularly your children, to stop cold, then you must be giving them foods that are rich in zinc.

8 Spinach

Spinach is the leading superfood that is excessive and best for your complete health. It is filled with digestion regulating the strength. Nonetheless, it also comprises vitamin C. Vitamin C is a controlling nutrient that can help in stopping the common cold and help in decreasing symptoms of illness.

All the points mentioned above are natural cold and flu remedies. These foods treat symptoms of colds and infections very effectively and quickly. The treatment is immediate without resorting to expensive creams, ointments, or medicines.

Author Bio:

Emylee is a wellness lifestyle writer. She loves sharing her thoughts and personal experiences related to natural remedies, yoga and fitness through her writing. She currently writes for How To Cure. She can connect with others experiencing health concerns and help them through their recovery journeys through natural remedies.

The Third Plague Pandemic in Europe

Plague has a long history on the European continent, with evidence of the disease dating back to the Stone Age. Plague epidemics in Europe during the First and Second Pandemics, including the Black Death, are infamous for their widespread mortality and lasting social and economic impact.

Yet, Europe still experienced plague outbreaks during the Third Pandemic, which began in China and spread globally at the end of the nineteenth century. The digitization of international records of notifiable diseases, including plague, has enabled us to retrace the introductions of the disease to Europe from the earliest reported cases in 1899, to its disappearance in the 1940s. Using supplemental literature, we summarize the potential sources of plague in Europe and the transmission of the disease, including the role of rats. Finally, we discuss the international efforts aimed at prevention and intervention measures, namely improved hygiene and sanitation, that ultimately led to the disappearance of plague in Europe.


The Third Plague Pandemic in Europe by: 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 4 September 2019

An apple carries about 100 million bacteria

Most microbes are inside the apple – but the strains depend on which bits you eat,
and whether you go organic

To the heroes among you who eat the whole apple: besides extra fiber, flavonoids and flavor, you’re also quaffing 10 times as many bacteria per fruit as your core-discarding counterparts.

Is this a good thing? Probably. But it might depend on how your apples were grown.

Published in Frontiers in Microbiology, a new study shows that organic apples harbor a more diverse and balanced bacterial community – which could make them healthier and tastier than conventional apples, as well as better for the environment.

You are what you eat

Nowhere more so than your bowel.

“The bacteria, fungi and viruses in our food transiently colonize our gut,” says study senior author Professor Gabriele Berg, of Graz University of Technology, Austria. “Cooking kills most of these, so raw fruit and veg are particularly important sources of gut microbes.”

To help us choose our colonic colonists wisely, Berg’s group analyzed the microbiome of one of the world’s favorite fruits: the apple.

83 million apples were grown in 2018, and production continues to rise,” says Berg. “But while recent studies have mapped their fungal content, less is known about the bacteria in apples.”

The researchers compared the bacteria in conventional store-bought apples with those in visually matched fresh organic ones. Stem, peel, flesh, seeds and calyx – the straggly bit at the bottom where the flower used to be – were analyzed separately.

Microbial diversity suggests organic apple advantage

Overall, the organic and conventional apples were occupied by similar numbers of bacteria.

“Putting together the averages for each apple component, we estimate a typical 240g apple contains roughly 100 million bacteria,” reports Berg.

The majority of the bacteria are in the seeds, with the flesh accounting for most of the remainder. So, if you discard the core – for shame! – your intake falls to nearer 10 million. The question is: are these bacteria good for you?

When it comes to gut health, variety is the spice of life – and in this regard, organic apples seem to have the edge.

“Freshly harvested, organically managed apples harbor a significantly more diverse, more even and distinct bacterial community, compared to conventional ones,” explains Berg. “This variety and balance would be expected to limit overgrowth of any one species, and previous studies have reported a negative correlation between human pathogen abundance and microbiome diversity of fresh produce.”

Specific groups of bacteria known for health-affecting potential also weighed in favor of organic apples.

“Escherichia-Shigella – a group of bacteria that includes known pathogens – was found in most of the conventional apple samples, but none from organic apples. For beneficial Lactobacilli – of probiotic fame – the reverse was true.”

And there may even be vindication for those who can “taste the difference” in organic produce.

“Methylobacterium, known to enhance the biosynthesis of strawberry flavor compounds, was significantly more abundant in organic apples; here especially on peel and flesh samples, which in general had a more diverse microbiota than seeds, stem or calyx.”

Consumer choice

The results mirror findings on fungal communities in apples.

“Our results agree remarkably with a recent study on the apple fruit-associated fungal community, which revealed specificity of fungal varieties to different tissues and management practices,” comments Birgit Wasserman, Berg protégé and lead author of the study.

Together the studies show that across both bacteria and fungi, the apple microbiome is more diverse in organically grown fruits. Since another study has shown that the apple fungal community is also variety-specific, the bacterial analyses too should be repeated in other cultivars.

“The microbiome and antioxidant profiles of fresh produce may one day become standard nutritional information, displayed alongside macronutrients, vitamins and minerals to guide consumers,” suggests Wasserman. “Here, a key step will be to confirm to what extent diversity in the food microbiome translates to gut microbial diversity and improved health outcomes.”

Research paper:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 3 September 2019

Paving the way for new flu drugs

Influenza polymerase (light cyan) in the process of synthesising messenger RNA (slate blue) by copying the genomic viral RNA template (yellow). IMAGE: Stephen Cusack / EMBL

When a virus infects and enters a host cell, the genomic material in the virus is both replicated to produce multiple copies of itself and transcribed into viral messenger RNA (mRNA). The viral mRNA can be read by the host cell’s protein production machinery, tricking it into making viral proteins. The viral proteins package the copies of the viral genome to make progeny viruses that are released from the cell to infect new hosts. An enzyme called a polymerase is responsible for both the transcription and replication of the viral genome and is therefore crucial to the successful propagation of the virus. The influenza virus, with genomic material made of RNA rather than DNA, is no exception to this modus operandi.

“Studying and understanding the unique mechanisms of transcription and replication used by influenza virus is essential to fight its spread,” explains EMBL group leader Stephen Cusack.

A decade long study

Stephen Cusack and his research group at EMBL Grenoble started to work on influenza polymerase more than 20 years ago. In 2014, the group published the first crystal structures of the complete polymerase machine. However, attempts to structurally characterise the different states of actively transcribing influenza polymerase have so far been unsuccessful.

“All studies so far have looked at the resting structure of the polymerase machine; we’ve never observed it actually doing anything,” says Tomas Kouba, a postdoc in the group who carried out much of the work.
Using X-ray crystallography and cryo-electron microscopy, both performed on state-of-the-art equipment at the European Synchrotron Radiation Facility in Grenoble, the group were able to determine, for the first time, atomic-resolution structures of different functional states of the influenza polymerase as it is actively transcribing genomic RNA into mRNA. In particular, it provides the first characterisation of the movements of the polymerase during the so-called nucleotide addition cycle, whereby each successive nucleotide is added to the growing mRNA chain.

Target point for new drugs

Despite its familiarity, the influenza virus – some strains of which are among the top ten most dangerous viruses in the world – is far from being well understood. Up to 500,000 people worldwide die from influenza each year, according to the World Health Organization, with potentially much higher mortality rates when a new pandemic flu strain emerges. Vaccination is not always effective and anti-influenza drugs are needed as a complementary treatment option.

As the viral polymerase is essential for the replication of the flu virus, it is a prime target for the development of new anti-influenza drugs. As such, the results gained by the EMBL group give new insights to help design the next generation of anti-influenza drugs. The advantage of drugs that stop the polymerase functioning is that it is much less likely that the virus will mutate in a way that would render the drug useless.

“Our results contribute the first snapshots of a movie that will show the complete transcription cycle of influenza polymerase from initiation to termination,” explains Cusack. The group will continue to use the powerful technique of cryo-electron microscopy to fill in the missing steps.

Source article

Kouba, T, Drncová, P, and Cusack, S. Structural snapshots of actively transcribing influenza polymerase. Nature Structural & Molecular Biology, published online 3 June 2019. DOI: 10.1038/s41594-019-0232-z

Monday, 2 September 2019

Addressing Bacterial Endotoxin Contamination Incidences in WFI

The presence of endotoxin in sterile pharmaceutical products presents a significant risk to patients. The primary source of endotoxin is pharmaceutical grade water, due to the potential for Gram-negative bacteria to be present in the water system or outlets. The water source of greatest impact is Water-for-Injections (WFI), because this is used as an ingredient water.

To examine this issue, Tim Sandle has written a review paper examining three significant water system endotoxin contamination case studies.

In any form of pharmaceutical manufacture water is one of the most serious potential sources of microbiological contamination.  Water cannot be totally excluded from sterile products manufacturing facilities.  The primary focus on endotoxin control in pharmaceutical manufacture is on controlling it at its source – water.  If endotoxin is not controlled at its source it has the potential to create difficulties through manufacture to the finished product, potentially leaving no recourse but rejection.  Endotoxin is practically impossible to remove terminally from pharmaceutical dosage forms.

Well-maintained and operated water systems should not see endotoxin detected on a regular basis. Where endotoxin detection occurs, this is typically due to a special cause event, signifying that something untoward has occurred with the design or operation of the water system. To illustrate what can sometimes occur, as providing some learning points, this article presents three cases studies relating to WFI systems, relating to three different pharmaceutical companies.

Sandle, T. (2019) Addressing Bacterial Endotoxin Contamination Incidences in WFI Systems: A Review of Case Studies, Journal of GXP Compliance, 23 (3): 1-10 at:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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