Sunday, 30 September 2018

Selecting disinfectants


Selecting the most appropriate cleaning and disinfectant agents is important. The cleanroom manager will need to be confident that the agents will work and are appropriate for the type of cleanroom. Care also needs to be taken as some agents are not compatible with each other.

In selecting detergents, it is important that:

a) The detergent is neutral and a non-ionic solution.

b) The detergent should be non-foaming.

c) The detergent should be compatible with the disinfectant (that is the residues of the detergent will not inactivate the disinfectant).

When selecting a disinfectant, points to consider are:

a) To satisfy GMP regulations, two disinfectants should be used in rotation. While scientifically this may not be necessary, many regulatory agencies expect to see two different disinfectants in place. For this, the two agents selected should have different modes of activity. It may be prudent for one of the disinfectants to be sporicidal.

b) The disinfectant should have a wide spectrum of activity. The spectrum of activity refers to the properties of a disinfectant being effective against a wide range of vegetative microorganisms including Gram-negative and Gram-positive bacteria.

c) Ideally the disinfectant should have a fairly rapid action. The speed of action depends upon the contact time required for the disinfectant to destroy a microbial population. The contact time is the period of contact when the surface to which the disinfectant is applied must remain wet.

d) Residues from organic materials or detergent residues should not interfere with the disinfectant.

e) Disinfectants used in higher grade cleanrooms (like ISO 14644 classes 5 and 7) must be supplied sterile or be sterile filtered by the cleanroom operators.

f) The disinfectant should be able to be used at the temperature at which the cleanroom operates. If a cleanroom is a cold store then it needs to be checked whether the disinfectant will work at that temperature.

g) The disinfectant should not damage the material to which it is applied or some other measures should be taken. Many sporicidal disinfectants are chlorine based and will damage material like stainless steel unless the residue is wiped away after use.

h) The disinfectant should be safe for operators to use and meet local health and safety laws.

i) The disinfectant should be cost effective and be available in the required formats like trigger spray bottles or ready-to-dilute concentrates.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 29 September 2018

Why do some microbes live in your gut while others don't?


Trillions of tiny microbes and bacteria live in your gut, each with their own set of genes. These gut microbes can have both beneficial and harmful effects on your health, from protecting you against inflammation to causing life-threatening infections. To keep out pathogens yet encourage the growth of beneficial microbes, scientists have been trying to find ways to target specific microbial genes.

A new study published in the scientific journal PLOS Computational Biology led by Patrick Bradley, a postdoctoral scholar in the Pollard lab, found a new approach to identify the genes that may be important to help microbes live successfully in the human gut.

New computational methods and DNA sequencing provide a solution to determine which microbes are usually present in a person's gut, and what genes are in the microbes' genomes. However, the researchers at Gladstone showed that just looking at the genes shared by gut microbes, without accounting for the microbes' common ancestry, can lead to many false discoveries.

See:

Patrick H. Bradley, Stephen Nayfach, Katherine S. Pollard. Phylogeny-corrected identification of microbial gene families relevant to human gut colonizationPLOS Computational Biology, 2018; 14 (8): e1006242 DOI: 10.1371/journal.pcbi.1006242

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 28 September 2018

Nanoparticle used to develop polio vaccine


A new nanoparticle vaccine developed by MIT researchers could assist efforts to eradicate polio worldwide. The vaccine, which delivers multiple doses in just one injection, could make it easier to immunize children in remote regions of Pakistan and other countries where the disease is still found.


While the number of reported cases of polio dropped by 99 percent worldwide between 1988 and 2013, according to the Centers for Disease Control, the disease has not been completely eradicated, in part because of the difficulty in reaching children in remote areas to give them the two to four polio vaccine injections required to build up immunity.

“Having a one-shot vaccine that can elicit full protection could be very valuable in being able to achieve eradication,” says Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research and one of the senior authors of the paper.

Robert Langer, the David H. Koch Institute Professor at MIT, is also a senior author of the study, which appears in the Proceedings of the National Academy of Sciences the week of May 21. Stephany Tzeng, a former MIT postdoc who is now a research associate at Johns Hopkins University School of Medicine, is the paper’s lead author.

“We are very excited about the approaches and results in this paper, which I hope will someday lead to better vaccines for patients around the world,” Langer says.

There are no drugs against poliovirus, and in about 1 percent of cases, it enters the nervous system, where it can cause paralysis. The first polio vaccine, also called the Salk vaccine, was developed in the 1950s. This vaccine consists of an inactivated version of the virus, which is usually given as a series of two to four injections, beginning at 2 months of age. In 1961, an oral vaccine was developed, which offers some protection with only one dose but is more effective with two to three doses.

The oral vaccine, which consists of a virus that has reduced virulence but is still viable, has been phased out in most countries because in very rare cases, it can mutate to a virulent form and cause infection. It is still used in some developing countries, however, because it is easier to administer the drops than to reach children for multiple injections of the Salk vaccine.

For polio eradication efforts to succeed, the oral vaccine must be completely phased out, to eliminate the chance of the virus reactivating in an immunized person. Several years ago, Langer’s lab received funding from the Bill and Melinda Gates Foundation to try to develop an injectable vaccine that could be given just once but carry multiple doses.

“The goal is to ensure that everyone globally is immunized,” Jaklenec says. “Children in some of these hard-to-reach developing world locations tend to not get the full series of shots necessary for protection.”

To create a single-injection vaccine, the MIT team encapsulated the inactivated polio vaccine in a biodegradable polymer known as PLGA. This polymer can be designed to degrade after a certain period of time, allowing the researchers to control when the vaccine is released.

“There’s always a little bit of vaccine that’s left on the surface or very close to the surface of the particle, and as soon as we put it in the body, whatever is at the surface can just diffuse away. That’s the initial burst,” Tzeng says. “Then the particles sit at the injection site and over time, as the polymer degrades, they release the vaccine in bursts at defined time points, based on the degradation rate of the polymer.”

The researchers had to overcome one major obstacle that has stymied previous efforts to use PLGA for polio vaccine delivery: The polymer breaks down into byproducts called glycolic acid and lactic acid, and these acids can harm the virus so that it no longer provokes the right kind of antibody response.

To prevent this from happening, the MIT team added positively charged polymers to their particles. These polymers act as “proton sponges,” sopping up extra protons and making the environment less acidic, allowing the virus to remain stable in the body.

In the PNAS study, the researchers designed particles that would deliver an initial burst at the time of injection, followed by a second release about 25 days later. They injected the particles into rats, then sent blood samples from the immunized rats to the Centers for Disease Control for testing. Those studies revealed that the blood samples from rats immunized with the single-injection particle vaccine had an antibody response against poliovirus just as strong as, or stronger than, antibodies from rats that received two injections of Salk polio vaccine.

To deliver more than two doses, the researchers say they could design particles that release vaccine at injection and one month later, and mix them with particles that release at injection and two months later, resulting in three overall doses, each a month apart. The polymers that the researchers used in the vaccines are already FDA-approved for use in humans, so they hope to soon be able to test the vaccines in clinical trials.

The researchers are also working on applying this approach to create stable, single-injection vaccines for other viruses such as Ebola and HIV.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 27 September 2018

Queen's University researchers make pneumonia breakthrough


A chance conversation between researchers at Queen’s University Belfast led to their combined expertise in developing a ground-breaking approach for the treatment of pneumonia.

The research team’s findings have recently been published in the prestigious leading Journal of Controlled Release.

Pneumonia is a serious inflammatory condition of the lungs, which is responsible for over 5% of all deaths in the UK each year, equivalent to over 3.2 million and also remains the leading infectious cause of death among children under five worldwide.

One of the most common causes of pneumonia is lung infection with the bacteria Klebsiella pneumoniae, the very bacteria that Professor Jose Bengoechea, Centre Director at the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University has spent much of his research career studying.

It was a chance conversation between Professor Bengoechea, Professor Cliff Taggart, a researcher at the Wellcome-Wolfson Institute for Experimental Medicine and their colleague Professor Chris Scott at the Centre for Cancer Research and Cell Biology that led to the discovery of this new groundbreaking treatment for pneumonia.

During this conversation the researchers realised that an idea Professor Scott was developing for cancer treatment could also be used for tackling deadly Klebsiella infections.

Professor Bengoechea explains: “This microbe is a particularly difficult bug to treat due to increasing number of isolates resistant to virtually all currently available antibiotics.

“It actually hides in the lung by sneaking inside immune cells, making it exceptionally hard to access with antibiotics. This hidden infection can then re-emerge and cause pneumonia in patients”.

It was the discussion of Professor Scott’s lab work using nanotechnology to target chemotherapy directly into cancer cells when the researchers realised that the same targeted approach could be used to get antibiotics directly to the deadly bacteria lurking in infected immune cells.

Professor Scott explains: “This is a perfect example of how thinking out of the box and combining very different expertise, you can have an eureka moment!

“These exciting research findings are very much in line with the research ethos of the University, which is centred on global challenges.

“Pneumonia remains a global health emergency. By developing this treatment that has proven to tackle this deadly strain of bacteria, our research partnership could change the lives of people across the world.”

The Queen's team are continuing further research within the next 5 years to achieve a better understanding of how best to treat patients with pneumonia with this specialised technology.

For the full publication in Journal of Controlled Release please see: JCR

Posted by Dr. Tim Sandle

Wednesday, 26 September 2018

Do Bacteria Ever Go Extinct?


Bacteria go extinct at substantial rates, although appear to avoid the mass extinctions that have hit larger forms of life on Earth
Bacteria go extinct at substantial rates, although appear to avoid the mass extinctions that have hit larger forms of life on Earth, according to new research from the University of British Columbia (UBC), Caltech, and Lawrence Berkeley National Laboratory. The finding contradicts widely held scientific thinking that microbe taxa, because of their very large populations, rarely die off.
The study, published today in Nature Ecology and Evolution, used massive DNA sequencing and big data analysis to create the first evolutionary tree encompassing a large fraction of Earth's bacteria over the past billion years.
"Bacteria rarely fossilize, so we know very little about how the microbial landscape has evolved over time," says Stilianos Louca, a researcher with UBC's Biodiversity Research Centre who led the study. "Sequencing and math helped us fill in the bacterial family tree, map how they've diversified over time, and uncover their extinctions."
Louca and colleagues estimate between 1.4 and 1.9 million bacterial lineages exist on Earth today. They were also able to determine how that number has changed over the last billion years—with 45,000 to 95,000 extinctions in the last million years alone.

"While modern bacterial diversity is undoubtedly high, it's only a tiny snapshot of the diversity that evolution has generated over Earth's history," says Louca.
Despite the frequent, steady extinction of individual species, the work shows that—overall—bacteria have been diversifying exponentially without interruption. And they've avoided the abrupt, planet-wide mass extinctions that have periodically occurred among plants and animals. Louca suspects that competition between bacterial species drive the high rate of microbial extinctions, leaving them less prone to sudden mass, multi-species extinctions.
Past speciation and extinction events leave a complex trace in phylogenies—mathematical structures that encode the evolutionary relatedness between existing bacterial species.
"This study wouldn't have been possible 10 years ago," says Michael Doebeli, UBC mathematician and zoologist, and senior author on the paper. "Today's availability of massive sequencing data and powerful computational resources allowed us to perform the complex mathematical analysis."
Next, Louca and his colleagues want to determine how the physiological properties of bacteria evolve over time, and whether their ecological diversity has also been increasing similarly to their taxonomic diversity. If this is true, it would mean that even ancient and relatively simple organisms such as bacteria still have the potential to discover novel ways to survive.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 25 September 2018

Microscope user guide


Keyscience have produced a new microscope guide, based on user case studies. The guide is called “VHX DIGITAL MICROSCOPES Voice of the Customer”.

“Browse through case studies from Ford Research, Smith & Nephew, Mitsubishi Heavy Equipment and Eastman Chemical and discover techniques to improve your own analysis, inspection or research processes.”



Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 24 September 2018

What Is the Link Between Pharma and Super Bugs?


Super bugs — antibiotic-resistant bacteria and viruses — are making an appearance in the news more and more often. These conditions were once treatable with the application of antibiotics, but new mutations have caused these bacteria and viruses to be resistant to those traditional applications. While mutations do occur in nature, these mutations aren't natural.

A guest post by Megan Ray Nichols

So, what is the link between Big Pharma and the creation of these super bugs?

Pharmaceutical Pollution


Pharmaceutical pollution is a bigger problem than most companies want to acknowledge. One study that looked into the waste created by pharmaceutical companies in India found that both antibiotics and anti-fungal drugs could be found in high amounts in the water supply around the factories. The study postulates that the drugs originated at the pharmaceutical factories in the area.

The presence of these drugs in the natural environment allows the microbes to build up a resistance to the drugs. So, when they re-encounter the drugs during treatment from a medical professional, the drug doesn't work.

This can turn otherwise treatable infections into fatal ones — and more of the world is starting to experience these drug-resistant infections more often than ever before.


Incomplete Guidelines

Pharmaceutical manufacturers are held to strict standards when it comes to creating new medications for the global marketplace. Each company is held to the Good Manufacturing Practices guidelines outlined by Food and Drug Administration (FDA). These guidelines act as strict quality control for the production of drugs and other medical implements, but the one thing these guidelines don't cover is pollution.

There is a breakdown in communication when it comes to pollution pharmaceutical industries generate. The international groups that are in charge of regulating the pharmaceutical industry have stated it is the responsibility of the countries where the drugs are being produced to regulate the pollution those factories are generating, but that's where communication breaks down. The countries are demanding international regulation for pharmaceutical pollution, and have argued that the lack of rules is the international community refusing to acknowledge the rampant threat that the lack of overall regulation has created. 

Increased Antibiotic Usage

Both humans and animals are using more antibiotics than ever before. It's estimated that human antibiotic use has climbed 36 percent in the last century. By 2030, upwards of 69 percent of livestock will be treated with antibiotics. In aquaculture, nearly 75 percent of the antibiotics used to treat the fish and other aquatic crops end up leaking into the surrounding environment.

The increase in antibiotic usage has allowed bacteria and viruses that wouldn't usually come into contact with antibiotics to develop a resistance to these treatments. Once that happens, the treatments that would typically heal the disease can no longer do their job.


Broken Promises

When super bugs first started to make an appearance in first-world countries, many pharmaceutical companies began to make promises that they would research these multi-drug resistant bugs and find a way to combat them without compromising the efficacy of current antibiotic based treatments.

As of August 2018, only 12 new antibiotics have been approved, and five of the main pharmaceutical companies that made those promises have abandoned their research into the MDR bacteria and viruses.

Super bugs are a big problem, and the lack of regulation of pharmaceutical waste — as well as the insufficient amount of research into these bugs — is causing the problem to get even bigger. The first step toward fixing this issue is the regulation of the pharmaceutical waste industry. Once the factories stop pouring waste into the surrounding environment, the dilemma of the super bug will be easier to address.

Pharmaceutical Microbiology Resources - antibiotics

Brexit uncertainty for pharmaceutical companies


Tim Sandle has written an article looking at the impact of Brexit on European pharmaceutical companies.

Here is the introduction:

“Of the different sectors of the British economy affected by the U.K.’s impending exit from the European Union, the pharmaceutical sector is one of the most significant. This relates to both the value of the market and the regulatory impact.

Companies who market pharmaceuticals in the European Union and in the U.K. will need to plan and make decisions in advance of the U.K.’s departure from the European Union in March 2019. Here companies need to decide whether they shift operation to Europe; or maintain a U.K. and European base; or exit the U.K. entirely. These decisions are not helped by the current cloud of political uncertainty and indecisiveness from the government.”

The reference is:

Sandle, T. (2018) Brexit uncertainty for pharmaceutical companies, Pharmig News, Issue 72, pp5-6

For a copy, please contact Tim Sandle at: pseudomonas@btinternet.com

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 23 September 2018

Bioanalytical method validation


The information in this final FDA guidance (“Bioanalytical Method
Validation Guidance for Industry”) applies to bioanalytical procedures such as chromatographic assays and ligand binding assays (LBAs) that quantitatively determine the levels of drugs, their metabolites, therapeutic proteins, and biomarkers in biological matrices such as blood, serum, plasma, urine, and tissue such as skin.

According to FDA: “This guidance helps sponsors of investigational new drug applications (INDs) or applicants of new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologic license applications (BLAs), and supplements validate bioanalytical methods used in human clinical pharmacology, bioavailability (BA), and bioequivalence (BE) studies that require pharmacokinetic, toxicokinetic, or biomarker concentration evaluation. This guidance can also inform the development of bioanalytical methods used for nonclinical studies that require toxicokinetic or biomarker concentration data. For studies related to the veterinary drug approval process such as investigational new animal drug applications (INADs), new animal drug applications (NADAs), and abbreviated new animal drug applications (ANADAs), this guidance may apply to blood and urine BA, BE, and pharmacokinetic studies.”

See: Validation

Posted by Dr. Tim Sandle

Saturday, 22 September 2018

Researchers discover the 'optimism' of E. coli bacteria


E. coli bacteria have different solutions to cope with different types of nutrient deprivation, including an 'optimistic' response to carbon limitations, according to a team of researchers. Carbon-limited cells generate a large number of inactive assembly lines (ribosomes), nitrogen-limited cells turn out proteins more slowly, and phosphorous-limited cells use only half as many assembly lines to generate the same number of proteins.

They were surprised to find that the bacteria had different strategies for dealing with each of the nutrient restrictions. Even more surprisingly, when carbon was limited, E. coli responded by building up its protein-production infrastructure, essentially preparing for a day when carbon would again be abundant.

It can help to think of the cell as a toy factory filled with individual assembly lines (ribosomes) producing toys (proteins), Gitai said. Carbon and nitrogen are key components of the toys, and phosphorus is vital to the assembly lines.

"When resources get tight, the cell has a decision to make," Gitai said. "What's the right usage of materials -- of its available resources? 'Am I going to devote resources into making more assembly lines or more toys?'"

The "toys," proteins, are the fundamental building blocks that allow cells to grow, divide or increase in mass. The faster a cell produces proteins, the faster it grows. Scientists have known for decades that there is a straightforward, linear relationship between the number of ribosomes (assembly lines) and the rate of protein (toy) production in E. coli. This has led to the widely accepted theory that each of these assembly lines is "optimized," operating constantly at its peak efficiency to produce proteins as fast as possible.

"Surprisingly, the current study radically changes this perspective," said Ned Wingreen, the Howard A. Prior Professor in the Life Sciences and a professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics (LSI) who was also a corresponding author on the paper.

The research team discovered that when they limited access to carbon and nitrogen, key ingredients in the toys, the cells grew slowly but steadily while also producing more and more assembly lines that sat idle.

"Under extreme carbon limitation, about half the ribosomes -- half the assembly lines -- are not even working," said Gitai. "That seems counterintuitive, right? That seems wasteful. Why build your factory so you have twice as many assembly lines as you need, and then not run half your assembly lines? We posited that that might be good for ramping up production when times change, and sure enough, that's what we saw."

These bacteria live in feast-or-famine environments like the human gut, where a long hungry period can end with the sudden arrival of a cheeseburger. "When all these new nutrients come in, you have the ability to produce faster," Gitai said. "You already made all those assembly lines -- they're ready, and now they can take off, now you can beat your competitors to the punch, because you don't have to invest in all this infrastructure, making all these new assembly lines. You have them set up."

This has interesting implications for E. coli competition strategies, said graduate student Hsin-Jung (Sophia) Li, who is the first author on the paper. "Maybe the goal of the bacteria is not to maximize the current growth," she said. "They might be preparing for better times -- more forward-looking."

"Overall, this work gives a new perspective on bacteria, and potentially other organisms, suggesting they evolved not only to deal with current conditions but also for life in a changing world," said Wingreen.


"It has been an exciting journey," said Junyoung Park, a 2016 Ph.D. graduate in chemical and biological engineering who is now a professor of chemical and biomolecular engineering at the University of California-Los Angeles. "We started with a simple observation -- nutrient-specific RNA-to-protein ratios -- but ended up with fascinating insights into the cell's competition strategies."
E. coli uses different strategies when different nutrients are limited, the researchers found. "Carbon-limited cells generate a large number of inactive assembly lines," Li said. "Nitrogen-limited cells turn out products more slowly. But phosphorus-limited cells -- this was the exciting part -- use only half as many assembly lines to generate the same number of toys."

The ribosome assembly lines depend on RNA, which is phosphorus-rich, so by limiting its availability, the researchers essentially made toy ingredients cheap but assembly lines very expensive.

"The first surprise was that there's a nutrient-specific story here, that we achieved the same growth rate three different ways," said Gitai. "But the real surprise was the phosphorus. We found that if we make the assembly lines more expensive, suddenly the same assembly lines can pump out toys at the same rate, using half as many assembly lines. That tells us that under the carbon- and nitrogen-limited conditions, those assembly lines were actually not working as fast as they possibly could."

This overturned the long-held model of the optimized ribosome and prompted the researchers to investigate the mechanisms at work in the ribosomes, using a combination of quantitative experiments, led by Li, buttressed by the modeling and theory work of Wingreen and Zhiyuan Li, an associate research scholar in the Princeton Center for Theoretical Science. They also collaborated with Christopher King, who graduated in 2017 with a physics concentration, and Joshua Rabinowitz, a professor of chemistry and LSI.


Converting the enormous quantities of biological data into a clear theory illustrates the "charm" of data science, said Zhiyuan Li, from processing the measurements into "individual pearls, and then stringing them together into a beautiful necklace by mathematical modeling that reveals the underlying connections."

"This paper is a great contribution to the community," said Ron Milo, principal investigator of the Department of Plant and Environmental Sciences at the Weizmann Institute of Science, who was not involved in this research. "It gives us better insight into how cells make decisions regarding their allocation of resources, which can be relevant for biotechnological production of value-added chemicals."

The research also raises a new question, said Gitai: "Do many bacterial species use this strategy? You could imagine that in a community of bacteria, there are some species that are optimists, some that are pessimists. ... It's kind of an appealing idea that it's this 'eternal optimism' of E. coli that allows it to trade off, if you will, between immediate benefit and the longer term. When times are bad, it's going to say, 'Okay, I'm not going to worry about doing as well as I possibly can right now, but I'll prepare for when times get better.'"


One of the biggest surprises of the research was that such a thoroughly studied bacteria still has tricks up its microscopic sleeves, said Sophia Li. "Even E. coli, arguably the most well-understood organism, can still give us new surprises and interesting biology to learn."

See:

Sophia Hsin-Jung Li, Zhiyuan Li, Junyoung O. Park, Christopher G. King, Joshua D. Rabinowitz, Ned S. Wingreen, Zemer Gitai. Escherichia coli translation strategies differ across carbon, nitrogen and phosphorus limitation conditions. Nature Microbiology, 2018; DOI: 10.1038/s41564-018-0199-2

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 21 September 2018

Depleting microbiome with antibiotics can affect glucose metabolism


A new study has found that mice that have their microbiomes depleted with antibiotics have decreased levels of glucose in their blood and better insulin sensitivity. The research has implications for understanding the role of the microbiome in diabetes. It also could lead to better insight into the side effects seen in people who are being treated with high levels of antibiotics.


The microbiome is the collection of microorganisms that live in an animal's body, many of which are essential for health. Previous studies have shown that mice whose microbiomes are deficient in certain types of bacteria are more likely to develop diabetes. There is also some evidence that certain microbes may be protective against diabetes.

The researchers didn't set out to look specifically at how antibiotic-induced depletion influences glucose levels. They wanted to look at the circadian (24 hour) rhythms of mouse metabolism when the microbiome is depleted. This type of research is often done with mice raised in germ-free environments.

After treating the mice, the investigators observed that there was a large decrease in the diversity of microorganisms present in their guts, as expected. When they looked at the metabolisms of the mice, they found that they were able to clear glucose from their blood much faster than expected.

Further studies showed that the colon tissue in the mice was acting as a kind of sink for the glucose -- absorbing the extra sugar and thereby reducing its levels in the blood. This behavior fit the observation that the mice had colons that were greatly increased in size.

The researchers then discovered that these metabolic changes were actually related to changes in liver function and to the bile acids that were being released by the liver. The mice did not have changes in body fat composition or in what they ate -- the two things that normally influence glucose metabolism and are known to play a role in type 2 diabetes in humans.

See:

Amir Zarrinpar, Amandine Chaix, Zhenjiang Z. Xu, Max W. Chang, Clarisse A. Marotz, Alan Saghatelian, Rob Knight, Satchidananda Panda. Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-05336-9

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 20 September 2018

EDQM publishes a new section dedicated to biotherapeutics


As public standards for the quality of medicines in Europe, the monographs and reference standards of the European Pharmacopoeia (Ph. Eur.) play a major role in ensuring the quality of biotherapeutics, thereby contributing to overall patient safety. By providing these recognised common standards for the quality of medicines and their components, the Ph. Eur. promotes public health and ensures the safety of medicines for patients. Ph. Eur. Standards are designed to meet the needs of all stakeholders, including industry, Official Medicines Control Laboratories (OMCLs) and regulatory authorities.

The new biotherapeutics section on the EDQM website summarises Ph. Eur. Commission activities and achievements in this field. In addition to clarification of the role of Ph. Eur. monographs in the biosimilars regulatory pathway, it describes the recently concluded P4-BIO pilot phase and the ongoing pilot phase on monoclonal antibodies (“MAB pilot phase”), explaining the strategy followed by the Ph. Eur. when setting requirements for the quality of this important class of biotherapeutics. It also describes various levels of flexibility integrated into Ph. Eur. texts, including those introduced recently to address the structural complexity, heterogeneity and compound diversity derived from different manufacturing processes of complex biotherapeutics.

See EDQM: https://www.edqm.eu/sites/default/files/press_release_epd_biotherapeutics_and_new_tg_june_2018.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 19 September 2018

How soil bacteria munch on plastics


Thin mulch films made of polyethylene are used in agriculture in numerous countries, where they cause extensive soil contamination. Researchers have now identified an alternative: films made of the polymer PBAT biodegrade in soils.

Our world is drowning in a flood of plastic. Eight million tons of plastic end up in the oceans every year. Agricultural soils are also threatened by plastic pollution. Farmers around the world apply enormous amounts of polyethylene (PE) mulch films onto soils to combat weeds, increase soil temperature and keep the soil moist, thereby increasing overall crop yields.

After harvest, it often is impossible for farmers to re-collect the entire films, particularly when films are only a few micrometers thin. Film debris then makes its way into the soil and accumulates in the soil over time, because PE does not biodegrade. Film residues in soils decrease soil fertility, interfere with water transport and diminish crop growth.

Researchers at ETH Zurich and the Swiss Federal Institute of Aquatic Science and Technology (Eawag) have now shown in an interdisciplinary study that there is reason to be hopeful. In their recent study, they demonstrate that soil microbes degrade films composed of the alternative polymer poly(butylene adipate-co-terephthalate) (PBAT). Their work has just been published in the journal Science Advances.

In their experiments, the researchers used PBAT material that was custom-synthesised from monomers to contain a defined amount of the stable carbon-13 isotope. This isotope label enabled the scientists to track the polymer-derived carbon along different biodegradation pathways in soil.

Upon biodegrading PBAT, the soil microorganisms liberated carbon-13 from the polymer.

Using isotope-sensitive analytical equipment, the researchers found that the carbon-13 from PBAT was not only converted into carbon dioxide (CO2) as a result of microbial respiration but also incorporated into the biomass of microorganisms colonizing the polymer surface.

The researchers are the first to successfully demonstrate -- with high scientific rigor -- that a plastic material is effectively biodegraded in soils.

Because not all materials that were labelled "biodegradable" in the past really fulfilled the necessary criteria. "By definition biodegradation demands that microbes metabolically use all carbon in the polymer chains for energy production and biomass formation -- as we now demonstrated for PBAT," says Hans-Peter Kohler, environmental microbiologist at Eawag.

The definition highlights that biodegradable plastics fundamentally differ from those that merely disintegrate into tiny plastic particles, for instance after exposure of the plastic to sunlight, but that do not mineralise.

In their experiment, the researchers placed 60 grams of soil into glass bottles each with a volume of 0.1 litre and subsequently inserted the PBAT films on a solid support into the soil.

After six weeks of incubation, the scientists assessed the extent to which soil microorganisms had colonised the PBAT surfaces. They further quantified the amount of CO2 that was formed in the incubation bottles and how much of the carbon-13 isotope the CO2 contained. Finally, to directly demonstrate the incorporation of carbon from the polymer in the biomass of microorganisms on the polymer surfaces, they collaborated with researchers from the University of Vienna.


At this stage, the researchers cannot yet say with certainty over which timeframe PBAT degrades in soils in the natural environment given that they conducted their experiments in the lab, not in the field. Longer-term studies in different soils and under various conditions in the field are now needed to assess the biodegradation of PBAT films under real environmental conditions.

See:

Michael Thomas Zumstein, Arno Schintlmeister, Taylor Frederick Nelson, Rebekka Baumgartner, Dagmar Woebken, Michael Wagner, Hans-Peter E. Kohler, Kristopher McNeill, Michael Sander. Biodegradation of synthetic polymers in soils: Tracking carbon into CO2and microbial biomass. Science Advances, 2018; 4 (7): eaas9024 DOI: 10.1126/sciadv.aas9024

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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