Friday, 6 December 2019

Immune response to influenza

It is estimated that influenza (flu) results in 31.4 million outpatient visits each year. New research from the University of Minnesota Medical School provides insights into how the body can protect itself from immunopathology during flu.

"One of the reasons people feel bad during flu and some people die from flu isn't actually the virus replication itself, but it is the immune system's attempt to control the virus that causes that damage," said lead author Ryan Langlois, PhD, assistant professor of Microbiology and Immunology at the Medical School. "That immune response, called immunopathology, is a very serious complication of flu."

Many people who get the flu recover in under two weeks because the immune system is able to clear the virus, leaving no trace of it in the body. Traditional theory thought this was accomplished by T cell-mediated killing of all infected cells. Several years ago, however, Langlois genetically engineered a flu virus that could permanently label infected cells, which led to the discovery that some infected cells do survive clearance.

The new study published in PLOS Pathogens examines why some infected cells evaded T cell-mediated killing in the lungs of a mouse model. Langlois and his team identified where the virus was in the lung and what types of cells it was in. They found that the formerly infected cells are able to clear the virus from the cell quick enough so that no remnants of the virus remained. Because T cells can't kill what they can't see, T cells need to see a virus in a cell to kill that cell.

After clearance, no virus exists in the lung, but the cells that used to be infected remain. The team found that those "survivor cells" actually divide and replenish themselves at a faster rate than uninfected cells.

"One can imagine that if T cells killed every infected cell, like people once thought they did, whole airways could be lost," Langlois said. "This study lends more data to the idea that preventing immunopathology is incredibly important, and it allows us to better understand the basic mechanisms of how the body regulates itself to prevent it."


Jessica K. Fiege, Ian A. Stone, Rebekah E. Dumm, Barbara M. Waring, Brian T. Fife, Judith Agudo, Brian D. Brown, Nicholas S. Heaton, Ryan A. Langlois. Long-term surviving influenza infected cells evade CD8 T cell mediated clearance. PLOS Pathogens, 2019; 15 (9): e1008077 DOI: 10.1371/journal.ppat.1008077

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 5 December 2019

Bacteria must be 'stressed out' to divide

A new study from EPFL scientists has found that bacteria use mechanical forces to divide, along with biological factors. The research, led by the groups of John McKinney and Georg Fantner at EPFL, came after recent studies suggested that bacterial division is not only governed by biology, but also by physics. However, this interplay is poorly understood.

Most bacteria are rod-shaped cells that multiply by doubling their length and dividing in the middle to yield two "daughter cells." Mechanisms that control these processes in space and time are critical for survival. The importance of these mechanisms becomes even clearer, given how pervasive bacteria are in everyday life, and how ubiquitous their use is in biotechnology.

The scientists studied bacteria that are very similar to the human pathogen that causes tuberculosis, which kills more people than any other infectious disease. To study the growth and division dynamics of these "mycobacteria" the scientists built a special instrument that combines optical and atomic force microscopy (AFM) to image and manipulate cells at the size scale of molecules.

The data showed that mycobacterial cell division requires mechanical forces in addition to previously identified division molecules (enzymes). Before a cell divides, there is a progressive build-up of mechanical stress in the cell wall, right at the point where the cell will divide.

The build-up eventually culminates in a millisecond-fast splitting of the cell into two new cells. Remarkably, when the researchers physically pressed on the bacteria with an ultra-sharp AFM needle, they caused instantaneous and premature cell division. "This experiment proves that physics is essential for this important biological process," says Georg Fantner.
But where is the biological part of the story? When a bacterial cell divides the two daughters must separate, a process mediated by enzymes that dissolve the molecular connections between them. The investigators found that this essential process could be bypassed by pressing on the nascent division site using the AFM needle.

"Our work demonstrates that biological enzymes and mechanical forces 'collaborate' to bring about the separation of daughter cells in bacterial cell division," says John McKinney.


Pascal D. Odermatt, Mélanie T. M. Hannebelle, Haig A. Eskandarian, Adrian P. Nievergelt, John D. McKinney, Georg E. Fantner. Overlapping and essential roles for molecular and mechanical mechanisms in mycobacterial cell division. Nature Physics, 2019 DOI: 10.1038/s41567-019-0679-1

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 4 December 2019

DNA-reeling bacteria yield new insight on how superbugs acquire drug-resistance

A new study from Indiana University has revealed a previously unknown role a protein plays in helping bacteria reel in DNA in their environment -- like a fisherman pulling up a catch from the ocean.

The discovery was made possible by a new imaging method invented at IU that let scientists see for the first time how bacteria use their long and mobile appendages -- called pili -- to bind to, or "harpoon," DNA in the environment.

By revealing the mechanisms involved in this process, the study's authors said the results may help hasten work on new ways to stop bacterial infection.
"The issue of antibiotic resistance is very relevant to this work since the ability of pili to bind to, and 'reel in,' DNA is one of the major ways that bacteria evolve to thwart existing drugs," said Ankur Dalia, an assistant professor in the IU Bloomington College of Arts and Sciences' Department of Biology, who is senior author on the study. "An improved understanding of this 'reeling' activity can help inform strategies to stop it."

The act of gobbling up and incorporating genetic material from the environment -- known as natural transformation -- is an evolutionary process by which bacteria incorporate specific traits from other microorganisms, including genes that convey antibiotic resistance.
The need for new methods to stop bacterial infection is growing since overuse of existing antibiotics, which speeds how quickly infectious organisms evolve to outsmart these drugs, is causing the world to quickly run out of effective treatments. By 2050, it's estimated that 10 million people could die each year from antimicrobial resistance.

Although they may look like tiny arms under a microscope, Dalia said, pili are actually more akin to an erector set that is quickly put together and torn down over and over again. Each "piece" in the structure is a protein sub-unit called the major pilin that assembles into a filament called the pilus fiber.

"There are two main motors that had previously been implicated in this polymerization and depolymerization process," added Jennifer Chlebek, a Ph.D. student in Dalia's lab, who led the study. "In this study, we show that there is a third motor involved in the depolymerization process, and we start to unravel how it works."

The two previously characterized "motors" that control the pili's activity are the proteins PilB, which constructs the pili, and PilT, which deconstructs it. These motors run by utilizing ATP, a source of cellular energy. In this study, IU researchers showed that stopping this process, which switches off the power to PilT, does not prevent the retraction of the pili, as previously thought.

Instead, they found that a third motor protein, called PilU, can power pilus retraction even if PilT is inactive, although this retraction occurs about five times more slowly. The researchers also found that switching off power to both retraction proteins slows the retraction process to a painstaking rate of 50 times slower. An unaltered pilus retracts at a rate of one-fifth of a micron per second.

Moreover, the study found that switching off PilU affects the strength of pilus retraction, which was measured by collaborators at Brooklyn College. The study also showed that PilU and PilT do not form a "hybrid" motor, but instead that these two independent motors somehow coordinate with one another to mediate pilus retraction.

"While the PilU protein had previously been implicated in pilus activity, its exact role has been difficult to determine because cells that lack this protein generally only have very subtle effects," Chlebek added. "Our observation that PilU can support pilus retraction in a mutant strain, when we threw a wrench in the PilT motor, was the key to unlocking how this protein aids in the depolymerization of pili."

The ability to precisely measure the pili's retraction rate -- and therefore precisely measure the impact of altering the proteins that affect this process -- was made possible by the ability to see pili under a microscope, which was not possible until the breakthrough imaging method invented at IU.

"The ability to fluorescently dye the pili was huge," Dalia said. "It allowed us to not only see the pili's activity but also measure it in ways which simply would not have been possible in the past."

Next, Chlebek aims to learn more about how the pili still retract when the power is switched off to both retraction motors, as well as explore how these insights could apply to understanding pili activity in other strains of bacteria.


Jennifer L. Chlebek, Hannah Q. Hughes, Aleksandra S. Ratkiewicz, Rasman Rayyan, Joseph Che-Yen Wang, Brittany E. Herrin, Triana N. Dalia, Nicolas Biais, Ankur B. Dalia. PilT and PilU are homohexameric ATPases that coordinate to retract type IVa pili. PLOS Genetics, 2019; 15 (10): e1008448 DOI: 10.1371/journal.pgen.1008448

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 3 December 2019

Bacterial resistance to ceftolozane-tazobactam examined

French investigators have described development of resistance to one of the last resort therapies used to treat extremely drug-resistant Pseudomonas aeruginosa. That resistance arose in a single patient over a scant 22 days. They subsequently identified the single nucleotide mutation in P. aeruginosa that caused the resistance.

Unexpectedly, the mutation partially re-sensitized P. aeruginosa to antimicrobials that have long been in use -- carbapenems and piperacilline-tazobactam -- to which the bacterium had been fully resistant.

That peculiar finding might prove beneficial for the treatment of extremely drug-resistant P. aeruginosa, by enabling use of piperacilline-tazobactam and carbapenems in such cases, as their minimum inhibitory concentrations (MIC) "decrease significantly," said principal investigator Leurent Dortet, PharmD, PhD. Nonetheless, he cautioned that clinicians would need to proceed with caution "since other resistance mechanisms might be present."
Dr. Dortet said that using higher doses of ceftolozane-tazobactam to begin with might limit the appearance of the mutation by killing the pathogens more rapidly. Dr. Dortet is Associate Professor of Microbiology, University Paris-Saclay, France.

To determine the mechanism responsible for causing this resistance, the team analyzed P. aeruginosa clinical isolates, both susceptible and resistant, that had been collected from this patient during the infection, and performed whole genome sequencing on these. That enabled the investigators to identify the single mutation in a gene that encodes a natural enzyme, cephalosporinase. (Overexpression of cephalosporinase causes resistance to nearly all antimicrobials of the ?-lactam family.)

Modeling the mutant enzyme in silico confirmed its role as the cause of resistance to ceftolozane-tazobactam, and resensitization to carbapenems and piperacilline-tazobactam.
"Our results demonstrated that resistance to this novel molecule can occur rapidly during treatment," said Dr. Dortet. He noted that at the time the investigators discovered the mutation, the antibiotic, ceftolozane-tazobactam, had only been in clinical use for a couple of years.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 2 December 2019

Visual inspection of particulate matter

Each final container of all parenteral preparations shall be inspected to the extent possible for the presence of observable foreign and particulate matter.

In relation to this a new article of interest has been issued:

This article highlights the key inspectional focal areas in visual inspection processes to guide the reader to re-assess their procedures and practices for enhancing visual inspection process. Each container of liquid parenteral product is required to be inspected for evidence of visible particles and any containers which are seen to be contaminated must be rejected. In addition, containers are also examined for flaws, cracks, misplaced seals etc. These are material issues which could compromise the integrity of the containers and therefore of the sterility of its contents. For staff tasked with the inspection, the inspector will check whether they can detect different particles (or microbial growth) based on their training and may esquire if frequent eye tests are carried out.

The reference is:

Saghee, M.R., Sandle, T. and Das, P. (2019) Regulatory inspection of sterile facilities – the focal points. Part 1 – Visual inspection of particulate matter, GMP Review, 18 (1): 13-18

Foe details, contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 1 December 2019

Pharmaceutical Microbiology Resources is 10 years old

Today marks an anniversary of sorts. This website - Pharmaceutical Microbiology Resources - is ten years old, and with over 3 million reads.

I began blogging and posting interesting research and my own thoughts on all things pharmaceutical microbiology (with the odd general science story or healthcare related snippet thrown in for good measure) due to a general lack of information. My biggest frustration was not finding out about new standards or publications of interest.

Over the past ten years, pharmaceutical microbiology has grown strongly and it continues to evolve into a respected and knowledgeable profession, distinct from other types of microbiology.

The evolution of pharmaceutical microbiology, outside the narrow of some academic interpretations (where the focus was often only on sterilization or antimicrobial efficacy) was driven by the voluminous and insightful work of Scott Sutton and those other pioneers who put together the Pharmaceutical Microbiology Forum in the U.S. and those other innovators who came up with the idea of Pharmig in the U.K. (which was driven by the energies of Poly Hajipieris) and continued with equal energy and commitment by Maxine Moorey and committee.

Over the years a number of individuals have made a significant contribution (based on those I've cited most often in my own writings) - Tony Cundell, Jeanne Moldenhauer, Luis Jimenez, Ed Tidswell, Ziva Abraham, Karen McCullough, Jim Agalloco, Jim Ackers, Nigel Halls, Michael Miller - and there are, of course, many others.

Promotion of pharmaceutical microbiology is evident with the PDA and PHSS and their journals, plus magazines like American Pharmaceutical Review, European Pharmaceutical Review and Cleanroom Technology.

For more in-depth analysis, Davis Healthcare International - operated by the pioneering Amy Davis - has issued a number of titles relating to pharmaceutical microbiology and related areas. I'm proud to have contributed to several DHI publications.

I'm aiming to continue with this site for a few more years and I welcome any contributions, industry news, links to articles of interest and so on.

Thank you for your support over the past decade.


Here are the ten most popular posts over the past ten years:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 30 November 2019

Transient and long-term disruption of gut microbes after antibiotics

Trillions of microbes in the intestine aid human health, including digestion of breast milk, breaking down fiber and helping control the immune system. However, antibiotic treatment is known to disrupt the community structure of these microbes -- 500 to 1,000 bacterial species that have a mainly beneficial influence.

A study at the University of Alabama at Birmingham now has tracked this disruption at the level of a strain of microbes replacing another strain of the same species in 30 individuals -- all of them young, healthy adults who would be expected to have stable microbial communities.
The UAB study used bioinformatic tools to analyze a previously described study of 18 individuals who had been given a single antibiotic, cefprozil, for a week. Their fecal samples were collected at pre-treatment, at the end of antibiotic treatment and at three months post-treatment. The UAB study also analyzed previously described data of 12 individuals who were given a combination of three antibiotics -- meropenem, gentamicin and vancomycin -- for four days. Their fecal samples were collected at pretreatment; at end of treatment; and at four, 38 and 176 days post-treatment. Six control individuals who did not receive antibiotics were also analyzed.

In general, the UAB researchers found that strains of the 10 most abundant species remained stable in controls. In the single antibiotic treatment individuals, 15 of 18 individuals had transient new strains post-treatment that, in turn, were replaced by the original strain by three months post-treatment.

In contrast, the triple-antibiotics individuals showed a significant increase of new strains that persisted as long as six months after treatment, as compared to the single antibiotic and the control individuals. Furthermore, the fraction of transient strains was also significantly higher in the multiple antibiotics individuals. This suggested a long-term change to an alternative stable microbiome state, Morrow says. These changes were not due to a difference in growth rates.


Hyunmin Koo, Joseph A. Hakim, David K. Crossman, Ranjit Kumar, Elliot J. Lefkowitz, Casey D. Morrow. Individualized recovery of gut microbial strains post antibiotics. npj Biofilms and Microbiomes, 2019; 5 (1) DOI: 10.1038/s41522-019-0103-8

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 29 November 2019

Single mutation changes function of bacteria's transporter proteins

Swapping a single amino acid in a simple bacterial protein changes its structure and function, revealing the effects of complex gene evolution, finds a new study published in the journal eLife. The study -- conducted using E. coli bacteria -- can help researchers to better understand the evolution of transporter proteins and their role in drug resistance.

Cells are bound by a thin membrane layer that protects its interior from the outside environment. Within this layer are transporter proteins that control which substances are allowed in and out of the cell. These transporters actively move substances across the cell membrane by loading cargo on one side of the layer, then changing their structure to release it on the other side.

Membrane transporters are typically made up of multiple repeating units. In more complex transporters, the genetic sequence for each of these structural units is fused together into a single gene that codes for the protein.

It is thought that the repeated pattern evolved from smaller membrane protein genes that had duplicated and fused together. But are there evolutionary advantages to having more complex transporters being produced from a single, fused gene?

To investigate this, researchers examined a simple transporter found in E. coli bacteria, which is plentiful in human and animal intestines. However, some strains of E. coli can cause serious illness and are increasingly resistant to antibiotics, which occurs when they pump out toxic compounds using transporters in their membrane. The E. coli transporter, called EmrE, contains two identical protein subunits that work together to move toxic molecules across the membrane and eliminate them from the cell.

Experiments revealed that changing a single amino acid -- the building blocks that make up proteins -- in one of the two protein subunits to make them slightly different from each other dramatically modified the transporter's structure and function. The subtle amino acid swap disrupted the balance of inward- and outward-facing proteins.

Importantly, changing the single amino acid altered the transporter's ability to remove toxic chemicals from E. coli and reduced the bacteria's resistance to drugs -- which may have future implications for drug development and combating antibiotic resistance.

The researchers note that the effects of a minor change to one of the identical halves of the EmrE transporter demonstrates how sensitive membrane transporters are to mutations.


Maureen Leninger, Ampon Sae Her, Nathaniel J Traaseth. Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations. eLife, 2019; 8 DOI: 10.7554/eLife.48909

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 28 November 2019

Mode of delivery at birth may play key role in shaping the child's skin microbiome

The maturation of skin microbial communities during childhood is important for the skin health of children and development of the immune system into adulthood, but only a few studies have analyzed the microbiota in young children. In a new study, investigators in China found that bacterial genera in children were more similar to those of their own mothers than to those of unrelated women. Their data suggest that the mode of delivery at birth could be an important factor in shaping the child's microbiome.

"To date, research into the maternal influence on her child's skin microbiome has been mostly limited to a narrow postpartum window in children younger than one year old and fewer studies have explored the maternal relationship with the child's microflora after infancy," explained lead investigator Zhe-Xue Quan, Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Institute of Biodiversity Science, School of Life Sciences, Fudan University, Shanghai, China. "Therefore, we expanded the scope of our analysis to include sampling from different body sites and direct comparison to the mother of the child in order to provide novel insights."

Investigators examined the changes in the skin microbiota and analyzed relationships between the skin microbiome and microenvironment as well as between the microbiota composition of children and mothers in 158 children between one and ten years old. The mothers of 50 of these children were randomly selected and recruited to represent different child age groups. Microbiota structures between the children and their mothers were compared using 16S rRNA gene amplicon sequencing. Samples were taken from three skin sites: center of the cheek; one quarter of the length of the forearm from the hand; and the center of the calf. Data for 474 samples (three skin sites per child) were pooled into 36 groups according to age, gender, and skin site.

Sample location and age were the primary factors determining a child's skin bacterial composition, which differed significantly among the three sites. However, there was negative correlation between the abundances of Streptococcus and Granulicatella and age. The relative abundances of most bacterial genera in children were more similar to those of their own mothers than those of unrelated women. The facial bacterial composition of 10-year-old children was strongly associated with whether they were born by Caesarian section or vaginal delivery.


Ting Zhu, Xing Liu, Fan-Qi Kong, Yuan-Yuan Duan, Alyson L. Yee, Madeline Kim, Carlos Galzote, Jack A. Gilbert, Zhe-Xue Quan. Age and Mothers: Potent Influences of Children’s Skin Microbiota. Journal of Investigative Dermatology, 2019; DOI: 10.1016/j.jid.2019.05.018

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 27 November 2019

Skin UV exposure reflected in poop

The Sun can indeed shine out of your backside, suggests research. Not because you’re self-absorbed, but because you’ve absorbed gut-altering UV radiation.

This is the first study to show that skin exposure to UVB light alters the gut microbiome in humans. Published in Frontiers in Microbiology, the analysis suggests that vitamin D mediates the change – which could help explain the protective effect of UVB light in inflammatory diseases like MS and IBD.

Ratifying rodent studies

Sun exposure, vitamin D levels and the mix of bacteria in our gut are each associated with risk of inflammatory conditions like MS and IBD. Scientists hypothesize that a causal chain links the three.

Exposure to UVB in sunlight is well-known to drive vitamin D production in the skin, and recent studies suggest that vitamin D alters the human gut microbiome. However, that UVB therefore causes gut microbiome changes, via vitamin D production, has so far been shown only in rodents.

In a new clinical pilot study, researchers tested the effect of skin UVB exposure on the human gut microbiome.

Healthy female volunteers (n=21) were given three one-minute sessions of full-body UVB exposure in a single week. Before and after treatment, stool samples were taken for analysis of gut bacteria – as well blood samples for vitamin D levels.

Rich as feces

Skin UVB exposure significantly increased gut microbial diversity, but only in subjects who were not taking vitamin D supplements during the (winter) study (n=12).

“Prior to UVB exposure, these women had a less diverse and balanced gut microbiome than those taking regular vitamin D supplements,” reports Prof. Bruce Vallance, who led the University of British Columbia study. “UVB exposure boosted the richness and evenness of their microbiome to levels indistinguishable from the supplemented group, whose microbiome was not significantly changed.”

The largest effect was an increase in the relative abundance of Lachnospiraceae bacteria after the UVB light exposures.

“Previous studies have linked Lachnospiraceae abundance to host vitamin D status,” adds Vallance. “We too found a correlation with blood vitamin D levels, which increased following UVB exposure.”

This indicates that vitamin D at least partly mediates UVB-induced gut microbiome changes.

The results also showed some agreement with mouse studies using UVB, such as an increase in Firmicutes and decrease in Bacteroidetes in the gut following exposure.

Getting to the bottom of UVB’s protective effect

“In this study we show exciting new data that UVB light is able to modulate the composition of the gut microbiome in humans, putatively through the synthesis of vitamin D,” Vallance sums up.

The study is not designed to show the exact mechanism by which the microbiome changes occur, but both UVB and vitamin D are known to influence the immune system.

“It is likely that exposure to UVB light somehow alters the immune system in the skin initially, then more systemically, which in turn affects how favorable the intestinal environment is for the different bacteria,” suggests Vallance.

“The results of this study have implications for people who are undergoing UVB phototherapy and identifies a novel skin-gut axis that may contribute to the protective role of UVB light exposure in chronic inflammatory diseases like MS and IBD.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 26 November 2019

A new approach to tackle superbugs

Scientists have uncovered a novel antibiotic-free approach that could help prevent and treat one of the most widespread bacterial pathogens, using nanocapsules made of natural ingredients.

Helicobacter pylori (H. pylori) is a bacterial pathogen carried by 4.4 billion people worldwide, with the highest prevalence in Africa, Latin America and the Caribbean.
Although the majority of infections show no symptoms, if left untreated the pathogen can cause chronic inflammation of the stomach lining, ulcers and is associated with an increased risk of gastric cancer.

In 2017, the World Health Organisation included H. pylori on its list of antibiotic-resistant "priority pathogens" -- a catalog of bacteria that pose the greatest threat to human health and that urgently need new treatments.

Current treatments involve multi-target therapy with a combination of antibiotics, but this has promoted the emergence of resistant strains.

Now, UK and German scientists have uncovered a novel antibiotic-free approach using only food- and pharmaceutical-grade ingredients, which are non-toxic and safe for consumption, to be used as a supplement to complement antibiotic current therapies.

The formulation is delivered through billions of bundled together nanocapsules, which are smaller than a human blood cell, and prevents the bacteria from attaching to and infecting the stomach cells.

The team, which includes researchers from the universities of Leeds, Münster and Erlangen, hope the nanocapsules could be used as a preventative measure, as well as helping eradicate H. pylori and reduce antibiotic resistant strains.


Bianca Menchicchi, Eleni Savvaidou, Christian Thöle, Andreas Hensel, Francisco M. Goycoolea. Low-Molecular-Weight Dextran Sulfate Nanocapsules Inhibit the Adhesion of Helicobacter pylori to Gastric Cells. ACS Applied Bio Materials, 2019; DOI: 10.1021/acsabm.9b00523

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 25 November 2019

Blockchain innovations for pharmaceuticals and healthcare

A blockchain is a time-stamped series of immutable record of data that is managed by a cluster of computers not owned by any single entity (this means it is ‘decentralized’). Each of these blocks of data (a ‘block’) are secured and bound to each other using cryptographic principles (the ‘chain’). This makes the blockchain an incorruptible digital ledger of transactions that can be programmed to record anything of value, such as time, temperature, vibration, costs and so on.

Blockchain in the full-blown sense has yet to be accepted by pharmaceutical  regulators; however, the U.S. FDA agreed in 20198 to a pilot study. This blog posts looks at what blockchain is and how it might work in the context of pharmaceuticals and healthcare. This post also looks at areas where blockchain can be directed and what advantages it can deliver to pharma. Of these different applications, avoiding the falsification of medicines is probably the most important.

Tim Sandle has written a new article for the IVT Network.

While blockchain as yet to take-off fully in the pharma world, across other industries (such as food and shipping) it is regarded as one of the most disruptive technologies within the digital transformation paradigm, introducing greater security and transparency to economic transactions. As soon as it become accepted by pharmaceutical regulators, it will change the industry permanently - passing information from A to B in a fully automated and safe manner.

Sandle, T. (2019) Blockchain innovations for pharmaceuticals and healthcare, IVT Network, at:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 24 November 2019

New species of choanoflagellate discovered

Scientists have found a new species of choanoflagellate. This close relative of animals forms sheets of cells that 'flip' inside-out in response to light, alternating between a cup-shaped feeding form and a ball-like swimming form. The organism could offer clues about animals' early evolution.

Choanoflagellates inhabit the no-man's-land of protozoans -- creatures that are clearly not bacteria, but also don't qualify as complex multicellular life, like plants or animals. Each choanoflagellate cell has a tail-like flagellum surrounded by a ring of tiny hairlike structures, like a sperm cell wearing a fluffy Elizabethan collar.

When C. flexa's sheets curl up into a ball with the flagella pointing outward, the ball swims quickly by waving the tail-like structures. Or the sheet can flip into a cup shape by unfolding and then curling in the opposite direction, in such a way that all the flagella face inside.

A series of experiments revealed that the organism reacts to light using a light-sensing protein and other molecules, some of which C. flexa must obtain from the bacteria they eat. What's more, King's team figured out the precise mechanism for the flip: the cells simultaneously flare their collars into a cone shape, bending the sheet of cells and causing a contraction similar to that of an animal's muscle. This inspired the team to look at other choanoflagellates, some of which turned out to have the same ability. The finding suggests this particular contracting mechanism likely pre-dates the first animals.


Thibaut Brunet, Ben T. Larson, Tess A. Linden et al. Light-regulated collective contractility in a multicellular choanoflagellate. Science, 2019 DOI: 10.1126/science.aay2346

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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