Saturday 28 December 2019

Mycoplasma Conference Summary

For further details see: Roche

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

Tuesday 24 December 2019

Happy Holidays!

I'd like to wish all readers of Pharmaceutical Microbiology all the best wishes for the Holiday season!

Thank you for supporting this website and our LinkedIn and Facebook groups.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

Monday 9 December 2019

Microbiology Roundtable

American Pharmaceutical Review has run another in its Microbiology Roundtable features. Here is an extract from Tim Sandle:

Q. In general, what are some of the current critical issues/trends facing pharmaceutical manufacturers in regards to microbiology testing and remediation?

Sandle:  One of the biggest issues is with time-to-result, which is affected by the (largely) continued dependency upon culture-based methods and which is symptomatic by the slow take-up of rapid microbiological methods. Being able to obtain data faster, enables better responses.

While rapid methods will undoubtedly help, it remains that contamination control and good design are the most important considerations. There is little value testing if a given process has not been correctly designed to minimize the ingress of contamination, Of the different routes in, the main one remains people and the way they behave. Be it sterile or non-sterile manufacturing, designing systems and putting in place barriers to reduce the opportunity for personnel to get close to the product are paramount.

The reference is:

Microbiology Roundtable (2019) Michael Reynier, Jordi Iglesias, Tony Cundell, Suzanne Williams, Frank Panofen, Paula Peacos, Tim Sandle, Quinton Inglet, Jonathan Swenson, American Pharmaceutical Review, pp86-91

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday 13 November 2019

Digital transformation of pharmaceuticals - what's new?

Here is my article on digital transformation of pharmaceuticals - "Becoming Pharma 4.0: How Digital Transformation Is Reshaping Pharmaceuticals".

The digital transformation of biopharmaceutical manufacturing is continuing at a rapid pace as companies attempt to mine the sources of data available. Innovations include predictive analytics, big data analytics, and creating the digital plant. Digital transformation offers a mechanism to revise its business model, to improve production processes, to design new drugs faster by using artificial intelligence to screen compounds and to increase responsiveness to customers. Furthermore, the volume of data processed by pharmaceutical firms shows no sign of slowing down. This means pharmaceutical companies must act quickly in terms of building core internal digital capabilities and moving beyond their traditional IT functions to all areas of the business.

See :

Sunday 3 November 2019

Good Distribution Practice: A Handbook for Healthcare Manufacturers and Suppliers

An excellent new two-volume book has been published, vital for those working in pharmaceuticals and healthcare:

Good Distribution Practice: A Handbook for Healthcare Manufacturers and Suppliers - Edited by Siegfried Schmitt.

A two-volume reference publication, discussing in detail global regulations and practices. Over 30 professionals and experts share their knowledge, interpret the regulations and provide a plethora of best-practice examples.

Volume 1
Following an introduction into the subject of Good Distribution Practice (GDP), the key topics covered in this volume relate to:
  • The applicable GDP regulations globally, including serialization
  • Qualified Person (QP) and Responsible Person (RP) in GDP
  • GDP as part of the Quality Management System (QMS)
  • Good Distribution Practice - the industry perspective
  • GDP Checklist
Volume 2

Following an introduction into the subject of Good Distribution Practice (GDP), the key topics covered in this volume relate to:
  • De-risking the supply chain
  • Serialisation and Packaging in Practice
  • Other chapters provide details about packaging materials. 
The authors not only introduce the readers to the options available, but more importantly help assure that the selection of packaging materials is linked to shipping routes, pharmaceutical material properties and lastly costs. 

The book is available from the PDA Bookstore:

Or from Amazon :

Volume 2

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday 31 October 2019

Robust Quality Audits Are The Solution To Avoiding Expensive Recalls

Compliance is an affirmative indication or judgement that the supplier of a product or service has met the requirements of the relevant specifications, contract or regulation; also the state of meeting the requirements. Compliance is something that meets both the text and the spirit of a requirement. This is the central message of the book Audit and Control for Healthcare Manufacturers” by Tim and Jennifer Sandle (published by DHI, http://www.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 28 October 2019

Biocontamination Control for Pharmaceuticals and Healthcare

A new book has been published – “Biocontamination Control for Pharmaceuticals and Healthcare” by written Tim Sandle. The book outlines a biocontamination strategy that tracks bio-burden control and reduction at each transition in classified areas of a facility. This key part of controlling risk escalation can lead to the contamination of medicinal products, hence necessary tracking precautions are essential. Regulatory authorities have challenged pharmaceutical companies, healthcare providers, and those in manufacturing practice to adopt a holistic approach to contamination control. New technologies are needed to introduce barriers between personnel and the environment, and to provide a rapid and more accurate assessment of risk. This book offers guidance on building a complete biocontamination strategy.
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday 22 October 2019

ISO 14644-16:2019 – Part 16: Energy efficiency in cleanrooms and separative devices

A new standard has been issued:

“This document gives guidance and recommendations for optimizing energy usage and maintaining energy efficiency in new and existing cleanrooms, clean zones and separative devices. It provides guidance for the design, construction, commissioning
and operation of cleanrooms.

This document covers all cleanroom-specific features and can be used in different areas to optimize energy use in electronic, aerospace, nuclear, pharmaceutical, hospital,
medical device, food industries and other clean air applications.

It also introduces the concept of benchmarking for the performance assessment and comparison of cleanroom energy efficiencies, while maintaining performance levels to ISO 14644 requirements.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 21 October 2019

Robust Quality Audits Are The Solution To Avoiding Expensive Recalls

Audit and Control for Healthcare Manufacturers” by Tim and Jennifer Sandle (published by DHI,

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday 17 October 2019

The Use of Microbiological Culture Media Article

Free-to-read article on microbial culture media best practices.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday 19 September 2019

NOW IS THE TIME for Animal Welfare in Pharma

Symposium - Animal Welfare in Pharma Join us at a symposium to celebrate the 60th anniversary of the 3Rs guiding principles (Reduction, Refinement and Replacement) for ethical use of animals in lab testing. Experts from the pharma industry will present ongoing initiatives to apply the 3Rs principles throughout the pharma process: from the drug development to production and batch release; there are many ways to avoid the use of animals.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday 18 September 2019

Microbial community with small diversity cleans up algal blooms

Algae blooms regularly make for pretty, swirly satellite photos of lakes and oceans. They also make the news occasionally for poisoning fish, people and other animals. What's less frequently discussed is the outsize role they play in global carbon cycling. A recent study now reveals surprising facts about carbon flow in phytoplankton blooms. Unexpectedly few bacterial clades with a restricted set of genes are responsible for a major part of the degradation of algal sugars.

Algae take up carbon dioxide (CO2) from the atmosphere and turn the carbon into biomass while releasing the oxygen back to the atmosphere. Fast algal growth during phytoplankton blooms leads to a massive transfer of carbon dioxide into algal biomass. But what happens to the carbon next?

"Once the algae die, the carbon is remineralized by microorganisms consuming their biomass. It is thus returned to the atmosphere as carbon dioxide. Alternatively, if the dead algae sink to the seafloor, the organic matter is buried in the sediment, potentially for a very long time," explains first author Karen Krüger from the Max Planck Institute for Marine Microbiology in Bremen. "The processes behind the remineralization of algal carbon are still not fully understood."

Thus, Krüger and her colleagues investigated microorganisms during spring algal blooms in the southern North Sea, at the island of Heligoland. They specifically looked at the bacterial use of polysaccharides -- sugars that make up a substantial fraction of the algal biomass. Together with colleagues from the Max Planck Institute, the University of Greifswald and the DOE Joint Genome Institute in California, Krüger carried out a targeted metagenomic analysis of the Bacteroidetes phylum of bacteria, since these are known to consume lots of polysaccharides. In detail, the scientists looked at gene clusters called polysaccharide utilisation loci (PULs), which have been found to be specific to a particular polysaccharide substrate. If a bacterium contains a specific PUL, that indicates it feeds on the corresponding algal sugar.

"Contrary to what we expected, the diversity of important PULs was relatively low," says Krüger. Only five major polysaccharide classes were being regularly targeted by multiple species of bacteria, namely beta-glucans (such as laminarin, the main diatom storage compound), alpha-glucans (such as starch and glycogen, also algal and bacterial storage compounds), mannans and xylans (typically algal cell wall components), and alginates (mostly known as slimy stuff produced by brown macroalgae). Of these five substrates, only two (alpha- and beta-glucans) make up the majority of substrates available to the bacteria during a phytoplankton bloom. This implies that the most important polysaccharide substrates released by dying algae are made up of a fairly small set of basic components.

"Given what we know of algal and bacterial species diversity, and the enormous potential complexity of polysaccharides, it came as no small surprise to see such a limited spectrum of PULs, and in only a relatively small number bacterial clades," co-author Ben Francis from the Max Planck Institute for Marine Microbiology sums up in an accompanying comment. "This was especially unexpected because previous studies suggested something different. An analysis of more than 50 bacterial isolates -- i.e. bacteria that can be cultured in the lab -- that our working group carried out in the same sampling region revealed a much broader diversity of PULs," he adds.
During the course of the algal bloom, the scientists observed a distinct pattern: In early bloom stages, fewer and simpler polysaccharides dominated, while more complex polysaccharides became available as the bloom progressed. This might be caused by two factors, Francis explains: "First, bacteria will in general prefer easily degradable substrates such as simple storage glycans over biochemically more demanding ones. Second, more complex polysaccharides become increasingly available over a blooms' course, when more and more algae die."

This study provides unprecedented insights into the dynamics of a phytoplankton bloom and its protagonists. A fundamental understanding of the bulk of glycan-mediated carbon flow during phytoplankton bloom events is now within reach. "Next, we want to dig deeper into processes underlying the observed dynamics," says Krüger. "Moreover, it will be interesting to investigate polysaccharide degradation in habitats with other carbon sources, such as the Arctic Seas or the sediment."


Karen Krüger, Meghan Chafee, T. Ben Francis, Tijana Glavina del Rio, Dörte Becher, Thomas Schweder, Rudolf I. Amann, Hanno Teeling. In marine Bacteroidetes the bulk of glycan degradation during algae blooms is mediated by few clades using a restricted set of genes. The ISME Journal, 2019; DOI: 10.1038/s41396-019-0476-y

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday 17 August 2019

Is anxiety linked to our gut microbiome?

Microbiome research has advanced considerably since the first results from the U.S. National Institutes of Health led Human Microbiome Project were released. One area of interest is the connection between our microorganisms and anxiety symptoms. At first glance, the connection between the array of different microorganisms that are found within the human gut and feelings such as anxiety is not an obvious one. However, there is a growing level of evidence that variations within microbial communities are influential upon metabolic processes.
Human microbiome
The human microbiome refers to the totality of microorganisms and their genetic interactions within a given niche. Our understanding of the microbiome has advanced following a study of 300 men and women, who volunteered to take part in an international study. The advancement in understanding relating to developments with the methods used to characterize the microorganisms (including metagenomics) and the in-depth nature of the study, relating to the sampling of many body parts over a prolonged period of time, and drawing upon of the subjects from different geographical locales.
FDA microbiologist prepares DNA samples for gel electrophoresis analysis
FDA microbiologist prepares DNA samples for gel electrophoresis analysis
FDA / File
With the specific effects in relation to the human gut, then the understanding by scientists of the gut-brain axis has increased during the past ten years, suggesting a bidirectional nature between the gut and brain microbiome interactions. This includes a connection relating to the pathophysiology and pathogenesis of irritable bowel syndrome (IBS), as an example.
In another research field, there is growing evidence of psychiatric and neurologic disorders like autism spectrum disorders, affective disorders, Parkinson's disease, and multiple sclerosis, being connected to the human gut microbiome.
The reason for this is that, with most people, the gut microbiota assist with the healthy functioning of the immune system. Furthermore, organisms assist with the metabolism by contributing inflammatory mediators, vitamins, and nutrients. Moreover, microbiologists have demonstrated that the intestinal microbiota can modulate communication between the intestinal tract and human brain via the nervous, immune, and endocrine systems.
It may be possible to treat superbugs with a predatory bacteria.
It may be possible to treat superbugs with a predatory bacteria.
University of Nottingham
However, when the intestinal microbial balance is altered, then changes occur and these can be manifest in terms of physical, and potentially mental, symptoms. One area being investigated in relation to a mental system is anxiety.
Anxiety is an emotion characterized by an inner turmoil. It is often accompanied by nervous behaviour, somatic complaints, and rumination. The condition includes subjectively unpleasant feelings of dread over anticipated events. When experienced regularly the individual may suffer from an anxiety disorder. The global incidence of anxiety disorder is estimated to be between 3-25 percent. Typical treatment for anxiety is usually psychopharmacological therapies and psychotherapy.
New research
With the new research, scientists have attempted to see if anxiety symptoms can be improved by regulation of intestinal microorganisms. By assessing some 3,334 published articles the researchers focus on 21 major studies. Across these studies,1,503 participants included "patients with IBS (10 studies), healthy controls (six studies) and other patients with chronic diseases such as chronic fatigue syndrome (CFS), rheumatoid arthritis (RA), obesity, fibromyalgia, and type 2 diabetes mellitus."
Of the 21 studies, 14 had chosen probiotics as interventions to regulate intestinal microbiota (IRIFs), and seven chose non-probiotic ways, such as adjusting daily diets. Those studies that utilized "interventions regulating intestinal flora" consisting of probiotics with Lactobacillus alone or a mixture of LactobacillusStreptococcus, and Bifidobacterium, showed some positive results. Overall, 11 of the 21 studies suggested a positive effect on anxiety symptoms by regulating intestinal microbiota, meaning that more than half (52 percent) of the studies showed this approach to be effective.
Some of the bacteria found by scientists in 3.5-billion-year-old fossils are now extinct  while oth...
Some of the bacteria found by scientists in 3.5-billion-year-old fossils are now extinct, while others are similar to contemporary microbes
To draw these conclusions the review was subjected to meta-analysis, considering the research design, subjects, interventions, and anxiety assessment scales. This drew out the connected between anxiety and disturbances to the gut microbiome and indicated that it may be possible to regulate the intestinal microbiota through the use of probiotics, although further research will be required.
The researchers conclude: "We find that more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota.
"There are two kinds of interventions (probiotic and non-probiotic interventions) to regulate intestinal microbiota, and it should be highlighted that the non-probiotic interventions were more effective than the probiotic interventions. More studies are needed to clarify this conclusion since we still cannot run meta-analysis so far."
Research paper
The new research has been published in the British Medical Journal, with the research paper titled “Effects of regulating intestinal microbiota on anxiety symptoms: A systematic review.”

Written by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday 1 August 2019

Microbes can grow on nitric oxide

Nitric oxide (NO) is a central molecule of the global nitrogen cycle. A study reveals that microorganisms can grow on NO. Their results change our view of the earth's nitrogen cycle and how microorganisms regulate the release of greenhouse gases from natural and human-made environments.

Intriguingly, long before there was oxygen on Earth, nitric oxide was available as a high-energy oxidant, and might have played a fundamental role in the emergence and evolution of life on Earth. A study by Max-Planck-scientist Boran Kartal and colleagues now published in Nature Communications sheds a new light on microbial transformations of this molecule. Yes they can -- with implications for our climate.

One major question about nitric oxide remained unanswered up to now: Can organisms use it to grow? "One would think so," Kartal explains, "as nitric oxide has been around since the emergence of life on earth." However, no microbe growing on NO has been found -- until now. Kartal and his colleagues from Radboud University in the Netherlands have now discovered that the anaerobic ammonium-oxidizing (anammox*) bacteria directly use NO to grow. In detail, these microorganisms couple ammonium oxidation to NO reduction, producing nothing but dinitrogen gas (N2) in the process.

The latter -- the sole production of N2 -- is particularly intriguing: Some microbes convert NO to nitrous oxide (N2O), which is a potent greenhouse gas. N2, in contrast, is harmless. Thus, each molecule of NO that is transformed into N2 instead of N2O is one less molecule adding to climate change. "In this way, anammox bacteria reduce the amount of NO available for N2O production, and reduce the amount of released greenhouse gas," Kartal explains. "Our work is interesting in understanding how anammox bacteria can regulate N2O and NO emissions from natural and human-made ecosystems, such as wastewater treatment plants, where these microorganisms contribute significantly to N2-release to the atmosphere."

Nitric oxide is a central molecule in the global cycling of nitrogen. "These findings change our understanding of the earth's nitrogen cycle. Nitric oxide has been primarily thought of as a toxin, but now we show that anammox bacteria can make a living from converting NO to N2," says Kartal. The present study raises new questions. "Anammox, a globally important microbial process of the nitrogen cycle relevant for the earth's climate, does not work the way we assumed it did." Moreover, other microbes than the ones investigated here could be using NO directly as well. Anammox bacteria are found all over the planet. "In this sense, the anammox microbes growing on nitric oxide could also be basically everywhere," Kartal continues.

Now, Kartal and his group at Max Planck Institute in Bremen are exploring different ecosystems from all around the world, hunting for specialized nitric oxide converting microorganisms. They want to understand better how microbes use NO in environments both with and without oxygen. This will probably pave the way to the discovery of new enzymes involved in nitric oxide transformation. "Basically, we want to understand how organisms can make a living on NO."

See: Ziye Hu, Hans JCT Wessels, Theo van Alen, Mike SM Jetten and Boran Kartal. Nitric oxide-dependent anaerobic ammonium oxidation. Nature Communications, 2019 DOI: 10.1038/s41467-019-09268-w

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday 31 July 2019

Big Investments for Human Microbiome Research

The Human Microbiome Project (HMP) was a U.S. National Institutes of Health (NIH) initiative that set the goal of identifying and characterizing the microorganisms which are found in association with both healthy and diseased humans, based on a budget of $115 million. The aim was to inform about human health or disease. Drawing on the wealth of data provided by the HMP, many companies are investing in microbiome based research.

Tim Sandle has written an article for BioPhrma Trends. Here is an extract:

"Capitalizing on new understanding of how imbalances in this ecosystem contribute to disease, a handful of startups aim to give physicians better weapons to fight conditions such as cancer, autoimmune disorders and infection. Examples include Vedanta Biosciences Inc, a start-up that has teamed up with New York University Langone Medical Center to study how bacteria can be used in the battle against tumors. Drug delivery is a related area with start-up Blue Turtle Bio utilizing bacteria from the gut microbiome as a drug delivery platform for supplemental enzymes intended to treat enzyme-deficient disease states."

To access, see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 29 July 2019

Contamination control hot topics

There are a number of challenges facing pharmaceutical and biopharmaceutical companies in relation to controlling contamination in their facilities. To address some of these issues American Pharmaceutical Review recently hosted a contamination control roundtable.

Taking part were: Tony Cundell, Paula Peacos, Tim Sandle and Jeanne Moldenhauer.

Here is an extract from Tim Sandle:

“The problems will vary between different facilities, and these will center on the different sources of contamination in relation to people, air, water, transfer of items, equipment cleanliness, and bioburden of starting materials. The most difficult challenges are invariably around people: how personnel behave in cleanrooms, how they are gowned, and whether they follow the correct procedures. Although the regulations around personnel have largely remained unchanged, its noticeable that the number of warning letters and other regulatory citations have increased. The reason for this must rest with training, knowledge and with time (in terms of allowing operators sufficient time to carry out their duties and to clean and disinfect effectively).

“Keeping track of data is also a challenge. With large facilities in particular, assessing microbial and particulate trends remains important so that appropriate actions can be taken promptly. Furthermore, it is important to understand when the process is leaning out of control, to enable personnel to be alerted to a potential change in the process.”

The reference is:

Cundell, T., Peacos, P., Sandle, T. and Moldenhauer, J. (2019) Contamination Control Roundtable, American Pharmaceutical Review, 22 (3): 44-47

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday 27 July 2019

EDQM inspections and trends of GMP deficiencies: Overview 2006 to 2018

A review of data from API inspections conducted by the EDQM between 2006 and 2018 is now available (PA/PH/CEP(18) 56 April 2019).

This document summarises the trends of deficiencies observed in EDQM inspections with reference to EU GMP and to the corresponding CEP dossiers.

This document is a review of data from API inspections conducted by the EDQM between 2006 and 2018. It covers: - the location of the inspections; - whether they were initial or re-inspections; - their outcome; - the distribution of the observed deficiencies to EU Good Manufacturing Practice (GMP) Part II area and criticality; - the frequency of the findings; - issues of data integrity.

For details, see:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 15 July 2019

An interview with Dr. Tim Sandle

Dr Tim Sandle is currently Head of Microbiology and Sterility Assurance at Bio Products Laboratory Limited. Here he talks to the Microbiology Society about his current role, his area of research and the importance of antimicrobial resistance (AMR) as a health issue. He also explains why he joined the Microbiology Society and offers advice for anyone thinking about a career change.

You are currently Head of Microbiology and Sterility Assurance: tell us more about your role with Bio Products Laboratory Limited.

I am responsible for heading up four departments. One is associated with supporting the manufacturing areas in terms of assessing cleanrooms for levels of microorganisms in the air and on surfaces for assessing product bioburden, microbial levels in water, screening samples for bacterial endotoxin and verifying that the finished product is sterile. The second area is associated with the development of novel microbial methods, the qualification of equipment, and dealing with regulatory submissions. The third area is to do with risk assessments, carried out in order to lower microbial contamination risks in process areas and to investigate when high microbial levels are recovered. The fourth area is linked to proactive practices to improve hygiene and to support new technologies. My role is to ensure these different entities connect together and to develop appropriate policies and standards in order to enhance sterility assurance.

Why did you choose to become a microbiologist?

I was always interested in biology: as a child, I was encouraged by my grandfather to take an interest in the natural world. I started off with an interest in biological sciences in general and was encouraged by a teacher to consider the importance of microbiology in health and disease.

Do you have any advice for anyone thinking about a career change and making a brave move from academia to industry?
The key attraction with industry is the ability to research and develop life-saving medicines and see these come to fruition. However, it is a different working experience and there are different types of pressures (these days both academia and industry are subject to increasing cost and time demands). Certainly, in industry there is a need to produce and release on schedule, otherwise this creates financial complexities. However, the work is very varied and there remains opportunities to engage in research and to produce papers. I’ve certainly managed to continue to contribute to peer-reviewed papers and book chapters. There also remains the opportunity to present at conferences.

Tell us about your biggest professional achievement(s) so far.

Some of the recent research I’ve been undertaking has concerned a partly overlooked issue of whether organisms that are resistant to antimicrobials have enhanced resistance to biocides. Although there is no direct evidence that organisms can acquire resistance to disinfectants, organisms that are resistant to antimicrobials may be harder to kill with the disinfectants commonly used in the pharmaceutical or healthcare setting. There is some evidence of this with some organisms, which calls for a renewed focus on aspects of disinfectant efficacy, like the minimum inhibitory concentration.

Tell us about your area of research?

The research is mostly applied. Over the past few years I’ve been working with microbiologists in Saudi Arabia, principally Dr Vijayakumar Rajendran, to determine the frequency of biocide resistant genes (e.g. qacA, qacE and cepA) in multidrug resistant bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and to correlate the presence or absence of resistant genes with biocides susceptibility. We’ve written several papers looking at different organisms and different biocides, assessing whether organisms that are antimicrobial resistant are also more resistant to common disinfectants. The research may have an impact on how pharmaceuticals and healthcare works, such as the need to reassess minimum inhibitory concentrations.

What have you done to try to maximise the impact of your research?

The research is ongoing and the full implications have yet to be realised; however, the research is showing a new dimension to the antimicrobial issue. The main thing in terms of impact is kicking-off discussion about overlooked areas in relation to AMR, which should help to encourage other researchers to consider different perspectives. Outside of this, I publicise where I can the importance of taking steps to reduce AMR, especially when different international campaigns are taking place. Social media provides a great outlet for this.

How important is AMR as a health issue?

It is an issue of great importance. Humans face the very real risk of a future without antibiotics. The implications of this are that life expectancy could fall due to people dying from diseases that are readily treatable today. In the last two decades, the rate at which bacteria are becoming resistant to current antibiotic treatments has substantially increased. For example, this trend is threatening the ability of medical staff to carry out routine operations or transplants in the future.

In your opinion, which areas of research are likely to have greatest impact on tackling AMR in the future?

Scientists have a role in addressing AMR even if they are not directly involved with AMR research or practices. This is by helping to promote best practices, such as avoiding the mis-prescribing of antibiotics to patients or though seeking better practices and alternatives to antibiotics in terms of rearing animals. One key research area that will have the greatest impact is in the search for new antimicrobials. There are some interesting ones in development, such as Dalvance, an intravenous drug that can treat skin and soft tissue infections; Oritavancin, a lipoglycopeptide with bactericidal activity against Gram-positive bacteria; and Teixobactin, a peptide-like secondary metabolite found in some bacteria that kills some Gram-positive bacteria and which has received the most media attention. The search for new antimicrobials, however, needs to continue, and the spectrum of searching needs to extend to areas of low human contact, such as deep in caves or parts of the oceans.

Do you have any advice for early career scientists who’d like to work in AMR?

First, research into AMR is a long process and there are many routes that do not lead to anything tangible. Patience is important. Second, potential candidate drugs to address AMR can come from the most unlikely of places, so keeping an open mind is also important.

The Microbiology Society is often seen as a Society for academics. What would you say to disperse this myth? What are the main benefits of being a member?

The Microbiology Society provides topical material for microbiologists in all sorts of occupations, not just academia. In recent years there has been a variety of different topics that connect what is being researched in universities to what needs to be developed by industry in order to meet healthcare demands – the hunt for new antimicrobials being a prime example. The Microbiology Society is so varied, and this richness leads to a range of different subject matter that enhances knowledge across both academia and industry. The sharing of ideas across these two sectors is to the benefit of all professional microbiologists. It provides an important arena for networking and sharing ideas across a range of different microbiological disciplines. It also plays a vital role in promoting the interaction between microbiologists and the general public, helping to educate and to engage.

And finally, why does microbiology matter?

Microbiology matters because it impacts across every aspect of society, from food production to global warming (such as toxic algal blooms); to the development of new medicines through biotechnology; for protecting the manufacture of medicines from contamination; and, of course, in protecting people from disease and with fighting diseases. Through being involved with any of these fields, you can make a difference.

Are you a member and interested in sharing stories about your research journey? Email March 2019


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday 1 July 2019

Sandle's Pharmaceutical Microbiology Dictionary

Pharmaceutical Microbiology, an applied branch of Microbiology, focused on study of micro-organisms associated with the manufacture of pharmaceuticals, primarily in minimizing the numbers in a process environment; ensuring that the finished product is sterile and excluding those specific strains that are regarded as objectionable from starting materials and water. The discipline is also associated with drug development, including the application of biotechnology. This dictionary provides definitions and descriptions of the leading terms association with pharmaceutical microbiology and related fields. The dictionary is designed to assist students and those who do not work directly in the field to understand the terminology; and as an aide-memoire for more experienced practitioners.

The book is available as an e-book or as a paperback via Amazon.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday 24 May 2019

New ‘interspecies communication’ strategy between gut bacteria and mammalian hosts

Bacteria in the gut do far more than help digest food in the stomachs of their hosts, they can also tell the genes in their mammalian hosts what to do.

A study published today in Cell describes a form of “interspecies communication” in which bacteria secrete a specific molecule–nitric oxide–that allows them to communicate with and control their hosts’ DNA, and suggests that the conversation between the two may broadly influence human health.

The researchers out of Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, and Harvard Medical School tracked nitric oxide secreted by gut bacteria inside tiny worms (C. elegans, a common mammalian laboratory model). Nitric oxide secreted by gut bacteria attached to thousands of host proteins, completely changing a worm’s ability to regulate its own gene expression.

The study is the first to show gut bacteria can tap into nitric oxide networks ubiquitous in mammals, including humans. Nitric oxide attaches to human proteins in a carefully regulated manner–a process known as S-nitrosylation–and disruptions are broadly implicated in diseases such as Alzheimer’s, Parkinson’s, asthma, diabetes, heart disease, and cancer.

The findings suggest nitric oxide is a general mechanism by which gut bacteria can communicate with mammalian hosts. Previous work to untangle communication lines to and from gut bacteria has primarily focused on rare molecules that bacteria secrete. The new findings are akin to uncovering a chemical language common across species, as opposed to single words, said senior author Jonathan Stamler, MD, director of the Institute for Transformative Molecular Medicine at Case Western Reserve University School of Medicine and president of the Harrington Discovery Institute at University Hospitals Cleveland Medical Center.

“There is tremendous complexity in the gut, and many researchers are after the next unusual substance produced by a bacterium that might affect human health,”

he says. With trillions of bacteria in the average gut, Stamler decided to look for a common language that all bacterial species might use.

“The enormity of the gut bacteria population and its relationship to the host predicts there will be general means to communicate that we humans can recognize.”

The researchers demonstrated the phenomenon by feeding developing worms bacteria that produce nitric oxide. They then selected one very important protein–argonaute protein, or ALG-1–that is highly conserved from worms to humans and silences unnecessary genes, including genes critical for development. When nitric oxide secreted by the bacteria attached to ALG-1, they developed malformed reproductive organs and died. Too much nitric oxide from bacteria commanded the worms’ DNA silencing proteins and impaired healthy development.

“Practically, animals will not let this happen,”

Stamler said. Instead, the authors speculate a mammalian host outside of a laboratory setting will adjust to accommodate changing nitric oxide levels. Said Stamler,

“The worm is going to be able to stop eating the bacteria that make the nitric oxide, or it will begin to eat different bacteria that makes less nitric oxide, or change its environment, or countless other adaptations. But by the same token, too much nitric oxide produced by our microbiome may cause disease or developmental problems in the fetus.”

The study adds to a growing body of evidence that bacteria living in the gut, determined by diet and environment, have a tremendous influence on mammalian health. Stamler imagines nitric oxide may represent an opportunity to manipulate this symbiotic relationship. Just as probiotics are designed to improve digestion, inoculating a person’s gut with bacteria to improve nitric oxide signaling is conceivable.

“I now think of this therapeutically, as a drug. There are tremendous opportunities to manipulate nitric oxide to improve human health.”

While nitric oxide and S-nitrosylation may be a general mode of interspecies communication with broad health implications, it will require additional future research. Will nitric oxide be the only chemical communication channel?

“We’re basically seeing a new field opening for general strategies of communication. There will be others.”


Stamler collaborated with several researchers from Case Western Reserve University School of Medicine on the new study, including first authors Puneet Seth, MD and Paishiun (Nelson) Hsieh, MD, PhD; Suhib Jamal; Liwen Wang, PhD; Mukesh Jain, MD; and Jeff Coller, PhD.

This research was supported in part by grants from the National Institutes of Health (R01-GM099921 to J.S.S., T32GM007250 and F30AG054237 to P.N.H, and R35HL135789 to M.J.).
Puneet, S., et al. “Regulation of microRNA machinery and development by interspecies s-nitrosylation.” Cell. DOI: 10.1016/j.cell.2019.01.037

Source: Microbiome Times

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