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.


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

Tuesday, 18 September 2018

Certification of suitability to the Monographs of the European Pharmacopoeia

A new document from the EDQM – ‘how to read a CEP’. This document has been created with the intention of clarifying the information to be concluded from a Certificate of suitability to the Monographs of the European Pharmacopoeia (CEP) for Industry and the Competent Authorities.

Specifically, this document describes in detail the information conveyed on a CEP. Marketing Authorisation (MA) applicants are advised to read existing guidance published by the Competent Authorities in their countries, or to contact them directly for advice, when using a CEP to replace the respective quality part of the CTD dossier related to that given source, or in any variation.

Competent authorities may contact the EDQM if they have questions concerning the content of the CEP which prevent them performing the evaluation of the MA application (MAA). If necessary, they may ask for the CEP assessment report. CEPs are normally accepted in all countries which are members of the Ph. Eur. Convention. CEPs may be accepted in countries which are not members of the Ph. Eur. Convention at the discretion of the authorities in those countries.


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 17 September 2018

Effective cleaning

To be able to achieve satisfactory disinfection, a good quality disinfectant is required. An ideal disinfectant should have a high inactivating capacity for a wide range of viruses, such as HIV and hepatitis, as well as being effective against bacteria, including tuberculosis. It should be safe to use and suitable for frequent application. Disinfectants are typically supplied as pre-saturated wipes which may be alcohol-based or non-alcohol based. This article considers the key requirements for a surface disinfectant and examines the comparative advantages of alcohol and non-alcohol wipes.

This is an extract from a new article by Tim Sandle, published in The Dentist.

"Infection control is integral to good dental practice, and surfaces need to be clean and maintained to a hygienic standard. In this context the term ‘hygiene’ refers to the elimination of potentially pathogenic microorganisms, including the bacteria that cause tuberculosis and MRSA infections."

The reference is:

Sandle, T. (2018) Effective cleaning. The Dentist, 34 (5): 82-83

For a copy, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 16 September 2018

Burkholderia cepacia in pharmaceutical and healthcare settings

Burkholderia cepacia is the name for a group or “complex” of bacteria that can be found in soil and water. B. cepacia bacteria are often resistant to common antibiotics. In recent years there has been a series of product recalls involving Burkholderia cepacia complex (BCC).

To address these concerns, pharmaceutical and healthcare manufacturers establish procedures (e.g., sanitary design, equipment cleaning, environmental monitoring) to prevent contamination of non-sterile drug products.

This topic has been covered in a new book chapter, written by Tim Sandle. An abbreviated abstract is:

This chapter discusses the general characteristics of the BCC group. This is followed by a review of the potential points of origin in pharmaceutical environmet6s, which are generally low-nutrient environments like water. This is followed by a review of the potential risks to patients that the organism presents. Such risks are contextualized in relation to patient population and product type.

The reference is:

Sandle, T. (2018): Burkholderia cepacia complex: Characteristics, products risks and testing requirements. In Reber, D. and Griffin, M. (Eds.) Microbial Control and Identification, DHI/PDA books, River Grove, USA, pp197-230. ISBN Number: 9781942911272

The book is available at the PDA bookstore.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 15 September 2018

How bacterial communities communicate over long distances

A concept known as 'percolation' is helping microbiologists explain how communities of bacteria can effectively relay signals across long distances. Once regarded as a simple cluster of microorganisms, communities of bacteria have been found to employ a strategy we use to brew coffee and extract oil from the sea. Percolation helps the microscopic community thrive and survive threats, such as chemical attacks from antibiotics.

The findings, led by Joseph Larkin and senior author Gürol Süel of UC San Diego, are published July 25 in the journal Cell Systems.

Biofilm communities inhabit locations all around us, from soil to drain pipes to the surface of our teeth. Cells at the edge of these communities tend to grow more robustly than their interior counterparts because they have access to more nutrients. To keep this edge growth in check and ensure the entire community is fit and balanced, the "hungry" members of the biofilm interior send electrochemical signals to members at the exterior. These signals halt consumption at the edge, allowing nutrients to pass through to the interior cells to avoid starvation.

In approaching their new study, the researchers sought to explain how bacterial communities are able to propagate these electrochemical communication signals. Unlike neurons that have designated structures to relay electrochemical signals known as axons, bacterial communities lack such sophisticated structures. This provoked the question of how bacteria could relay signals so effectively over long distances within the community.

After sifting through vast amounts of bacterial data, the UC San Diego researchers began collaborating with Purdue University's Andrew Mugler and Xiaoling Zhai, who proposed the idea that percolation theory could explain how bacterial communities may be propagating signals from cell to cell.

Percolation theory has been around since the 1950s and has helped physicists describe how signals are transmitted across a medium or network of diverse components. In a coffee maker, hot water percolates through individual coffee grounds into a carafe. In the oil industry, drillers maximize their yield by extracting petroleum from percolated sands, where the bedrock is porous enough to allow oil to flow over a large area.

In a community of bacteria, signals pass from cell to cell in a connected path over a distance of hundreds of cells. Using fluorescence microscopes, the researchers were able to track individual cells that were "firing" (transmitting a signal). The scientists found that the fraction of firing cells and their distribution in space precisely matched theoretical predictions of the onset of percolation. In other words, the bacterial community had a fraction of firing cells that was precisely at the tipping point between having no connectivity and full connectivity among cells, also known as a critical phase transition point.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 14 September 2018

Mutual Recognition Agreement between the E.U. and the U.S.

The European Union has updated the ‘question and answer’ document that covers the new mutual recognition agreement between the European Union and the U.S., much of it relating to inspections.

The document is called “Questions & Answers on the impact of Mutual Recognition Agreement between the European Union and the United States as of 1 June 2018”, and it can be found here:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 13 September 2018

Hurricane Harvey samples saddled with antibiotic-resistant genes

Rice University scientists have released the first results of extensive water sampling in Houston after the epic flooding caused by Hurricane Harvey. They found widespread contamination by E. coli, likely the result of overflow from flooded wastewater treatment plants.

The microbial survey showed high levels of E. coli, a fecal indicator organism, trapped in homes that still contained stagnant water weeks after the storm, as well as high levels of key genes that indicate antibiotic resistance.

The study led by Rice environmental engineer Lauren Stadler appears in the American Chemical Society journal Environmental Science & Technology Letters. A pair of National Science Foundation RAPID grants helped the team collect and analyze samples.

Rice environmental engineers Stadler, Qilin Li and Pedro Alvarez and their students were on the front lines, even before Harvey subsided, to take samples from floodwaters near the overflowing Brays and Buffalo bayous, in public spaces and inside and outside residential homes to compare their microbial content. Samples of stagnant water were taken from homes that had been closed off for more than a week, while others were taken from homes that had floodwater flowing through them.

Early samples from each location carried elevated levels of E. coli. But most striking was the fact that sampled water and, later, sediment showed abundant levels of two indicator genes, sul1 and intI1, that mark the presence of antibiotic-resistant bacteria, even weeks after the flood. In particular, samples from floodwaters inside closed homes showed concentrations of sul1 were 250 times greater and intI1 60 times greater in than in bayou samples.


Pingfeng Yu, Avery Zaleski, Qilin Li, Ya He, Kris Mapili, Amy Pruden, Pedro J. J. Alvarez, Lauren B. Stadler. Elevated Levels of Pathogenic Indicator Bacteria and Antibiotic Resistance Genes after Hurricane Harvey’s Flooding in Houston. Environmental Science & Technology Letters, 2018; DOI: 10.1021/acs.estlett.8b00329

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Burkholderia cepacia - Risks in Context for Non-Sterile Pharmaceutical Products (Webinar)

Drug manufacturers of non-sterile, water-based drug products have seen recent product recalls due to Burkholderia cepacia complex. Regulatory agencies expect pharmaceutical manufacturers to be testing environments, water and products for the organism and putting remedial measures in place. In order to test effectively, microbial methods need to be suitably qualified. The qualification of methods is challenging. Attend this webinar to learn more about this microorganism of concern, and to learn about its origins, risk factors, means of mitigation and methods of detection.


Date: Thursday, 20 September 2018 | Time: 10:00 AM PDT, 01:00 PM EDT | Duration: 60 Minutes

Burkholderia cepacia complex (BCC) organisms can survive or multiply in a variety of non-sterile and water-based products because it is resistant to certain preservatives and antimicrobial agents. This makes the organism a risk in terms of non-sterile aqueous products. Detecting BCC bacteria is also a challenge and requires validated testing methods that take into consideration the unique characteristics of different BCC strains. This webinar discusses where the organism may be found, how to detect it and what to do if it is present in the manufacturing environment.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 12 September 2018

New ICH Guidelines Q13 & Q14

The ICH Assembly agreed to begin work on two new Q topics for ICH harmonisation. These are:

Continuous manufacturing (Q13).
Analytical Procedure Development and Revision of Q2(R1) Analytical Validation (Q2(R2)/Q14).

Work will now begin on developing formal concept papers and work plans. See:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 11 September 2018

Permanent Cure of Your Missing Teeth

There are some common reasons why people lose their teeth, some of the major causes are old age, gum diseases, damage through trauma or failed dental work, etc. 

A guest post by Dr. Madhvi Nagpal.

Once a tooth has been lost, it has to be replaced for two primary and important reasons:
  • For restoring your teeth as even one missing tooth space in your mouth can affect your other teeth.
  • For your self-confidence.
There are a number of treatments for missing teeth, including tooth supported crowns, bridges, removable dentures. Considering these treatments might be a good decision, but not for long-term, as all these treatments are quite temporary and not that comfortable at all.

You have to choose a permanent solution for this, which is a dental implant. A dental implant is an artificial tooth that works like a real tooth. It imitates your tooth root and acts as an anchor for placing one or more artificial teeth. When a natural tooth is lost, an implant is inserted in the space left behind by the lost tooth. It is the best solution for a single or multiple missing tooth, but is more expensive than a dental bridge.
A dental implant is made up of Titanium metal which is biocompatible meaning it is easily accepted by the human body. It is lightweight but also the strongest metal and gives maximum strength.

If you have heard about it, you already know that it is very expensive. The dental implant cost in the USA, London, Canada, Australia is approximately $3000, but in India, the price of dental implant is 3 to 4 times lesser than any other developed country, that too under a professional doctor’s team.

Dental tourism, a term for medical vacation or a planned holiday, is where you can explore north India's beauty, culture, and ancient architectures like the Taj Mahal, India Gate, Qutub Minar, Fatehpur Sikri, etc.

The quality of dental treatment is as important as the cost of the treatment & India has been able to make a mark in the world market of dental tourism because of quality dental treatments offered by highly qualified dental professionals. All these treatments you can find at Dr. Madhvi's Dental Clinic. You will find various dental treatments like latest dental procedures including dental implants, root canal treatment, tooth-colored crowns, veneers & bridges, smile makeover, fixed teeth, complete dentures, removable partial denture, laser dentistry, etc. at competitive prices.

About the Author:

Dr. Madhvi Nagpal and her team of doctors have been practicing dentistry in New Delhi, India for the last 12 years. They use the latest equipment and materials in the dental treatments and follow the latest trends in dentistry. She has treated over 100 thousand patients during her practice & is an experienced dentist with a specialization in Dental Implants.

 Brought to you by Pharmaceutical Microbiology

Monday, 10 September 2018

New PIC/S Guidance Documents

The following new PIC/S Guidance documents have been adopted:

PIC/S Aide-Memoire on “CrossContamination in Shared Facilities” (PI 043- 1).

The purpose of this Aide-Memoire is to assist GMP inspectors in the assessment of the risks to the product from cross-contamination in shared facilities. This document provides guidance for GMP inspectors to use in preparation for, and performance of, inspections. It promotes a risk-based approach.

PIC/S Guidelines on the formalised risk assessment for ascertaining the appropriate GMP for excipients of medicinal products for human use (PI 045-1).

PIC/S Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (PI 046-1).

PIC/S Guidelines on the principles of GDP for active substances for medicinal products for human use (PI 047-1).

Also, the following Chapters and Annex of the PIC/S GMP Guide have been revised:
  • Chapter 3 on “Premises and Equipment”;
  • Chapter 5 on “Production”;
  • Chapter 8 on “Complaints and Product Recall”;
  • Annex 17 on “Real Time Release Testing and Parametric Release”.
  • The revised Chapters are based on the equivalent Chapters of the EU GMP Guide with some minor differences in terms of language.
See PIC/S:

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 9 September 2018

Why sepsis from a staph infection causes organ failure

For patients diagnosed with a Staphylococcus aureus infection, often referred to as a staph or MRSA infection, every minute counts. The bacteria create havoc in the body. The immune system goes into overdrive. The heightened immune response can lead to sepsis, which kills 30 to 50 per cent of the people who develop it. In Canada, sepsis is the 12th leading cause of death.

Scientists have known for some time that one of the reasons a staph infection is so deadly is that the bacteria send out a toxin, known as Alpha Toxin (AT), which quickly worsens sepsis. University of Calgary scientists at the Cumming School of Medicine's (CSM) Snyder Institute for Chronic Diseases have discovered the most important target of the toxin and how to neutralize the danger.
Using a process that allows scientists to see what's happening inside living animals, called intravital microscopy, researchers discovered that the toxin causes platelets to respond abnormally in mice. Platelets' primary role is to help stop bleeding in mammals after injury. What's relatively unknown is that platelets also play a role in the body's defenses against bacteria. Normally, platelets coat bacteria to prevent the spread of a microbe throughout the patient. However, during sepsis caused by staph infection, as the amount of toxin in the bloodstream increases, the platelets aggregate to form clumps. Those clumps deposit in the liver and kidneys, causing serious damage and eventually organ failure.


Bas G.J. Surewaard, Ajitha Thanabalasuriar, Zhutian Zheng, Christine Tkaczyk, Taylor S. Cohen, Bart W. Bardoel, Selina K. Jorch, Carsten Deppermann, Juliane Bubeck Wardenburg, Rachelle P. Davis, Craig N. Jenne, Kendall C. Stover, Bret R. Sellman, Paul Kubes. α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis. Cell Host & Microbe, 2018; DOI: 10.1016/j.chom.2018.06.017

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 8 September 2018

Gut bacteria byproduct protects against Salmonella

Researchers at the Stanford University School of Medicine have identified a molecule that serves as natural protection against one of the most common intestinal pathogens.

Propionate, a byproduct of metabolism by a group of bacteria called the Bacteroides, inhibits the growth of Salmonella in the intestinal tract of mice, according to the researchers. The finding may help to explain why some people are better able to fight infection by Salmonella and other intestinal pathogens and lead to the development of better treatment strategies.

The researchers determined that propionate doesn't trigger the immune response to thwart the pathogen. Instead, the molecule prolongs the time it takes the pathogen to start dividing by increasing its internal acidity.

Salmonella infections often cause diarrhea, fever and abdominal cramps. Most people recover within four to seven days. However, the illness may be severe enough to require hospitalization for some patients.

Salmonella causes about 1.2 million illnesses, 23,000 hospitalizations and 450 deaths nationwide each year, according to the Centers for Disease Control and Prevention. Most cases are caused by contaminated food.

The findings could also influence treatment strategies. Treating Salmonella infections sometimes require the use of antibiotics, which may make Salmonella-induced illness or food poisoning worse since they also kill off the "good" bacteria that keep the intestine healthy, according to Monack. Using propionate to treat these infections could overcome this limitation.


Amanda Jacobson, Lilian Lam, Manohary Rajendram, Fiona Tamburini, Jared Honeycutt, Trung Pham, Will Van Treuren, Kali Pruss, Stephen Russell Stabler, Kyler Lugo, Donna M. Bouley, Jose G. Vilches-Moure, Mark Smith, Justin L. Sonnenburg, Ami S. Bhatt, Kerwyn Casey Huang, Denise Monack. A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection. Cell Host & Microbe, 2018; DOI: 10.1016/j.chom.2018.07.002

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 7 September 2018

Identification and antibiotic‐susceptibility profiling of infectious bacterial agents: a review of current and future trends

A new paper of interest "Identification and antibiotic‐susceptibility profiling of infectious bacterial agents: a review of current and future trends".

Here is the abstract:

"Antimicrobial resistance is one of the most worrying threats to humankind with extremely high healthcare costs associated. The current technologies used in clinical microbiology to identify the bacterial agent and profile antimicrobial susceptibility are time‐consuming and frequently expensive. As a result, physicians prescribe empirical antimicrobial therapies. This scenario is often the cause of therapeutic failures, causing higher mortality rates and healthcare costs, as well as the emergence and spread of antibiotic resistant bacteria. As such, new technologies for rapid identification of the pathogen and antimicrobial susceptibility testing, are needed. This review summarizes the current technologies, and the promising emerging and future alternatives for the identification and profiling of antimicrobial resistance bacterial agents, which are expected to revolutionize the field of clinical diagnostics."

For details, see the Biotechnology Journal

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 6 September 2018

Why bacteria survive in space

In professor George Fox's lab at the University of Houston, scientists are studying Earth germs that could be contaminating other planets. Despite extreme decontamination efforts, bacterial spores from Earth still manage to find their way into outer space aboard spacecraft. Fox and his team are examining how and why some spores elude decontamination.

To gain access into the uber-sanitized clean rooms at NASA's Goddard Space Flight Center in Greenbelt, Maryland, the world's largest clean room, or the Jet Propulsion Laboratory in Caltech, California, employees pass through a series of lobbies. One, with adhesive floor mats, traps dirt carried on shoes. Another, about the size of an old phone booth, delivers a forced-air shower where dozens of air jets blow away dirt and debris. Only after these sterilization measures can they don the bodysuits, head covers and other disinfected regalia.

And still, bacteria survive and have been carried onboard the International Space Station and found on the Mars Rover. The ability of bacteria to survive extreme conditions could potentially lead to a process called 'forward contamination.'

As with natural selection, the cleaning process inside clean rooms will eventually kill off the weaker bacteria while a stronger strain adapts and is unphased by the cleansers.

The Fox team studied non-pathogenic (non-disease-causing) bacteria that belong to the genus Bacillus and produce highly resistant spores. They were isolated from cleanrooms and spacecraft assembly facilities at the Jet Propulsion Laboratory.

They sequenced the complete genome of two strains resistant to peroxide and radiation: B. safensis FO-36bT and B. pumilus SAFR-032. Then they compared the genomes of those strains and that of another strain, B. safensis JPL-MERTA-8-2, with bacteria known to produce spores that are vulnerable to peroxide and radiation, such as the strain B. pumilus ATCC7061T. The B. safensis JPL-MERTA-8-2 strain was isolated from the Mars Odyssey Spacecraft and associated facilities at the Jet Propulsion Laboratory and later also found on the Mars Explorer Rover (MER) before its launch in 2004.

By comparing the blueprints of the four strains, they found 10 genes that are unique to the FO-36b, that are not found in any other organisms (including other Bacillus strains). That is 10 genes whose functions are unknown -- or 10 suspects for why spores of B. safensis FO-36bT are resistant to peroxide and radiation, although it is not immediately obvious that the presence or absence of any specific gene or combination of genes is responsible for the variations in resistance seen.

As it turns out, four of these genes are found on phage elements of the bacterial strain. Phage, short for bacteriophage, is a virus that infects bacteria. Phages are major facilitators for transferring genes between microbes.

For details see:

Madhan R. Tirumalai, Victor G. Stepanov, Andrea Wünsche, Saied Montazari, Racquel O. Gonzalez, Kasturi Venkateswaran, George E. Fox. Bacillus safensis FO-36b and Bacillus pumilus SAFR-032: a whole genome comparison of two spacecraft assembly facility isolatesBMC Microbiology, 2018; 18 (1) DOI: 10.1186/s12866-018-1191-y

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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