Sunday, 19 November 2017

Biocidal cleaners may spread multidrug resistance in MRSA


Multidrug resistance to MRSA and reinfection with MRSA, said corresponding author Jonathan Shahbazian, MPH, were the most important in this study. The study also showed that whether used in humans or companion animals, the antibiotic clindamycin was not associated with the risk of multi-drug resistant bacteria in the home.

Treatment with mupirocin, an antibiotic used to treat skin infections and to eradicate MRSA from the nasal passages in order to prevent its spread from sneezes, is weakly associated with mupirocin resistance in the household environment.

In the study, the investigators collected samples from the home environments and companion animals of households enrolled in a large randomized controlled trial, which took place over a 14 month period. They tested whether household-wide efforts to eradicate MRSA -- which included daily use of nasal mupirocin ointment and chlorhexidine body wash -- were successful in reducing recurrence of MRSA among adults and children who had previously been diagnosed with a MRSA skin or soft tissue infection. They repeated sampling in 65 homes three months after the residents had been treated for MRSA, or, as a control, after they had been educated about MRSA.

The investigators concluded that a better understanding of what causes home environmental MRSA to become multidrug resistant, and thus harder to treat, could help in identifying which households are more likely to harbor multidrug resistant MRSA, so that these could be targeted for eradication of the pathogen.

See:

J. H. Shahbazian, P. D. Hahn, S Ludwig, J Ferguson, P Baron, A Christ, K Spicer, P Tolomeo, A. M. Torrie, W. B. Bilker, V. C. Cluzet, B Hu, K Julian, I Nachamkin, S. C. Rankin, D. O. Morris, E Lautenbach, M. F. Davis. Multidrug and mupirocin resistance in environmental methicillin-resistant Staphylococcus aureus (MRSA) collected from the homes of people diagnosed with a community-onset (CO-) MRSA infection. Applied and Environmental Microbiology, 2017; AEM.01369-17 DOI: 10.1128/AEM.01369-17



Posted by Dr. Tim Sandle

Saturday, 18 November 2017

Examining the lifestyles of microbes


Scientists are identifying and characterizing more microbes each year using DNA sequencing technologies. As each new species is sequenced, scientists add it to the microbial "tree of life," creating a virtual census of what's there.

Turns out it's not an easy job. To put things in perspective, scientists aren't sure how many microbes even exist. Estimates vary widely from millions to trillions.

University of Delaware professor Jennifer Biddle and Rosa Leon-Zayas, who completed post-doctoral work at UD earlier this year, recently described new details about microbes known as Parcubacteria in a paper published in Environmental Microbiology.

The Parcubacteria were found in sediment samples collected by James Cameron within the Challenger Deep region of the Mariana Trench during the Deepsea Challenge Expedition. Leon-Zayas' doctoral advisor, Doug Bartlett at Scripps Institution of Oceanography, was a chief scientist on the expedition.

"From a scientific perspective, Challenger Deep was an invaluable opportunity to collect samples from the deepest part of the ocean," said Leon-Zayas, the paper's lead author, now an assistant professor at Willamette University.

Scientists traditionally have learned how microbes work by growing and studying them in petri dishes and beakers. It wasn't until DNA sequencing advanced to include the ability to separate and test microbes present in environmental samples (such as soils or sediments) that scientists realized they had missed a huge portion of bacteria now called the Candidate Phyla Radiation (CPR).

One group of CPR microbes called the Parcubacteria had been seen in the groundwater and shallow sediments of a few places on land, but it had only been intensively studied in sediment samples from an aquifer near Rifle, Col.

When Cameron collected sediment samples at the bottom of the trench, the scientists discovered that many different species of Parcubacteria live there, too.

"We were interested in seeing if the microbes living at the bottom of the ocean had the same lifestyle as the microbes living in soils in Rifle, Colorado," said Biddle, a marine microbiologist and associate professor in the College of Earth, Ocean, and Environment's School of Marine Science and Policy.

Leon-Zayas used a sorting technique to separate the microbial cells from the sediment particles so that scientists could amplify and sequence the microbe DNA. The researchers then characterized the individual microbial genomes. Based on the genes that are present in the genome -- sections of DNA that define what metabolisms a cell is capable of -- scientists can infer what the bacteria is doing.

This genomic sequencing revealed that Parcubacteria from the deep sea have a fairly simple metabolism; but the genomes were larger than that of their terrestrial cousins and even had a few extra features. In particular, these features indicated the bacteria may be able to perform anaerobic respiration, using things like nitrate to breathe instead of oxygen.

Parcubacteria also seemed to have more proteins and enzymes associated with cold environments, not surprising since the bottom of the Mariana Trench is cold and dark.

"It makes sense that organisms at the bottom of the ocean might have to be more self-sufficient. The environment is extreme and there isn't as much food," Biddle said.

See:

Rosa León-Zayas, Logan Peoples, Jennifer F. Biddle, Sheila Podell, Mark Novotny, James Cameron, Roger S. Lasken, Douglas H. Bartlett. The metabolic potential of the single cell genomes obtained from the Challenger Deep, Mariana Trench within the candidate superphylum Parcubacteria (OD1). Environmental Microbiology, 2017; 19 (7): 2769 DOI: 10.1111/1462-2920.13789



Posted by Dr. Tim Sandle

Friday, 17 November 2017

Bacterial signalling in sharper resolution


The complex signalling networks bacteria use to adapt to their environments have become clearer following new research.

John Innes Centre researchers used a study of the plant-growth promoting bacterium Pseudomonas fluorescens to develop an advanced analysis method which, they hope, will increase our capacity to understand plant and human diseases.

Until recently, investigations into bacterial signalling have tended to look at different aspects of gene regulation in isolation. Building on these individual approaches, the John Innes team used a range of lab, computational and mathematical techniques to integrate data obtained from multiple different microbiological experiments.

This approach has enabled them to build a comprehensive 'signalling map' for the key bacterial protein Hfq, which controls virulence and stress responses in many clinically and agriculturally important species.

Dr Jacob Malone, the project leader associated with the work explained: "Our technique allows us to follow every gene and protein in a bacterial cell, and say how it changes and at what level that change occurs, in response to a given signal input.

"We are using the same data sets as previous studies but we have developed a way of integrating the data using mathematics and programming. If you consider the individual elements of a movie: the photography, the soundtrack and the script; by combining them you get a whole movie -- something greater than the sum of the parts. This is the same principle, only with genetics."

See:

Lucia Grenga, Govind Chandra, Gerhard Saalbach, Carla V. Galmozzi, Günter Kramer, Jacob G. Malone. Analyzing the Complex Regulatory Landscape of Hfq – an Integrative, Multi-Omics Approach. Frontiers in Microbiology, 2017; 8 DOI: 10.3389/fmicb.2017.01784



Posted by Dr. Tim Sandle

Thursday, 16 November 2017

ISO/IEC 17025 moves to final stage of revision


Calibration as well as testing and analysing a sample is the daily practice of more than 60 000 laboratories worldwide, but how can they reassure customers about the reliability of their results?

Over the years, ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories, has become the international reference for testing and calibration laboratories wanting to demonstrate their capacity to deliver trusted results. The International Standard, published jointly by ISO and IEC (International Electrotechnical Commission), contains a set of requirements enabling laboratories to improve their ability to produce consistently valid results.


However, the laboratory environment has changed dramatically since the standard was last published, leading to the decision to revise the standard and integrate significant changes. Steve Sidney, one of the Convenors of the working group revising the standard, explains: “The last version of ISO/IEC 17025 was published in 2005. Since then, market conditions have changed and we felt we could bring some improvements to the standard.”
Heribert Schorn, working group Convenor who also participates in IECEE (System of Conformity Assessment Schemes for Electrotechnical Equipment and Components), adds: “The revision was needed to cover all the technical changes, technical developments and developments in IT techniques that the industry has seen since the last version. Additionally, the standard takes into consideration the new version of ISO 9001.”

This standard is of high significance for the IEC Conformity Assessment Community as it outlines the basic requirements for testing within all Conformity Assessment Schemes and Programmes operating within the IECEE, IECEx, IECQ and IECRE Conformity Assessment Systems.

The review was started in February 2015 as a result of a joint proposal by the International Laboratory Accreditation Cooperation (ILAC) and the South African Bureau of Standards (SABS), who is a member of ISO and hosts the IEC National Committee. The standard’s revision process has now reached the Final Draft International Standard (FDIS) stage, the last leg of development before publication.

The main changes:

The revision of ISO/IEC 17025 takes into account the activities and new ways of working of laboratories today. The main changes are as follow:

The process approach now matches that of newer standards such as ISO 9001 (quality management), ISO 15189 (quality of medical laboratories) and ISO/IEC 17021-1 (requirements for audit and certification bodies). The revised standard puts the emphasis on the results of a process instead of the detailed description of its tasks and steps.

With a stronger focus on information technologies, the standard now recognizes and incorporates the use of computer systems, electronic records and the production of electronic results and reports. Modern-day laboratories work increasingly with information and communication technologies and the working group felt it was necessary to develop a chapter on this topic.

The new version of the standard includes a chapter on risk-based thinking and describes the commonalities with the new version of ISO 9001:2015, Quality management systems – Requirements.

The terminology has been updated to be more in step with today’s world and the fact that hard-copy manuals, records and reports are slowly being phased out in favour of electronic versions. Examples include changes to the International Vocabulary of Metrology (VIM)and alignment with ISO/IEC terminology, which has a set of common terms and definitions for all standards dedicated to conformity assessment.


A new structure has been adopted to align the standard with the other existing ISO/IEC conformity assessment standards such as the ISO/IEC 17000 series on conformity assessment.

The scope has been revised to cover all laboratory activities including testing, calibration and the sampling associated with subsequent calibration and testing.


Using ISO/IEC 17025 facilitates cooperation between laboratories and other bodies. It assists in the exchange of information and experience and helps harmonize standards and procedures, as Warren Merkel, another Convenor of the working group, explains. “ISO/IEC 17025 impacts the results delivered by laboratories in a number of ways. The standard requires them to meet criteria for competence of their personnel, the calibration and maintenance of their equipment and the overall processes they use to generate the data. This requires laboratories to think and operate in a way that ensures their processes are under control and their data are reliable.” Results also gain wider acceptance between countries when laboratories conform to the standard.

Developed jointly by ISO and IEC in the Committee on conformity assessment (CASCO), the new version of ISO/IEC 17025 will replace the 2005 version and is scheduled for publication at the end of this year.


Posted by Dr. Tim Sandle

Wednesday, 15 November 2017

Past, present, and future perspectives on the LAL reagent


Q&A covering past, present, and future perspectives on the LAL reagent


Since the introduction of the LAL reagent roughly 50 years ago, three methods of testing have been primarily used. how has your company used these methods?

JD: Actually, we use all four methods: gel-clot, kinetic turbidimetric, kineticchromogenic – and the PTS™. These methods are used to test and release incoming raw materials and to evaluate intermediate formulation buffers that are subsequently used to produce licensed LAL products. Our accessory products also benefit from the use of these methods prior to release. Finally, we leverage all of these techniques in developing and validating LAL test methods for customer-specific products.

TS: We began with the gel-clot test, which worked fine for water samples although it proved to be somewhat laborious for testing final products. Bio Products Laboratory was one of the first laboratories in the UK to adopt turbidimetric testing. This was in 1990, and technologies have improved greatly since then. We use turbidimetric testing today to test water samples (WFI and purified), intermediate products, finished product, and for other applications, such as testing container-closures for levels of endotoxin. We have also used LAL to screen for glucans.
How did the introduction of the LAL test change our industry?

TS: In terms of moving away from rabbit pyrogen testing this was very significant. It not only resulted in less animal testing being conducted, it also sped up the time-to-result and placed control of the test back into the hands of individual companies. Moreover, LAL results – where endotoxin is the pyrogen of concern – are more accurate and can be trended.JD: The LAL test has dramatically improved the quality of drug products and medical devices since its introduction. It has allowed the production process to be monitored in a way not possible before, resulting in better and safer products entering the healthcare system.

Furthermore, the relative low cost of the test allowed more samples to be tested. This expanded the scope of in-process control testing.
What are the key trends in endotoxin and LAL testing? What advances have been made?

JD: A major trend in LAL testing today is the continual movement away from the traditional gel-clot reagents and into more rapid quantitative methods. The data from these systems is also becoming more and more directly interfaced with a company’s LIMS system for more sophisticated data management and electronic record keeping. Obviously, it’s difficult to top the invention of LAL and replacement of the rabbit pyrogen test; however, there have been two significant LAL developments that really stand out. One is the development of quantitative LAL-based methods, which allow customers to quantify levels of endotoxin in their samples below their limits and to look for trends that could proactively prevent failures. Following that, the FDA approval of the Endosafe®-PTS™, the first point-of-use endotoxin detection system, allows users to rapidly test for the presence of endotoxin in the manufacturing environment for real-time results. Celebrating its 10-year anniversary, the Endosafe®- PTS™, has revolutionized the healthcare industry, enabling QC laboratories to improve sample management, decrease testing time and accelerate product production while still being compliant with global pharmacopoeial methods.

TS: In terms of trends, the scope of testing seems to be everincreasing with more tests being conducted.

Regarding advances, in recent years these have been towards rapid methods and with test systems having a larger capacity, to ease sample throughput. Recombinant lysates have also appeared on the market which seems as effective as lysate derived from the Limulus crab.

LW: Robust and more sensitive assays are the top two trends in the endotoxin detection industry; while portable systems and comprehensive analytical tools, like WinKQCL™ Endotoxin Detection and Analysis Software, are also becoming more essential to end-users.

In addition, there is a growing awareness of the need to conserve diminishing animal sources that are used for pharmaceutical and medical device testing. Bacterial endotoxin testing is rapidly evolving from an industry that relied heavily upon animal resources, i.e. rabbits and horseshoe crabs, to the development of biochemical assays as an endotoxin detector. This is evident in the increasing number of endusers who are now evaluating and validating alternative methods, like recombinant Factor C and the Monocyte Activation Test (MAT), instead of LAL-based tests for endotoxin detection. A little over ten years ago, Lonza recognized this progression of the industry and was the first company to develop a recombinant method for endotoxin detection that did not rely on the blood from the horseshoe crab: the PyroGene™ Recombinant Factor C Assay. Factor C, the first component of the horseshoe crab clotting cascade activated by endotoxin, is the critical component that allows for detection of endotoxin without isolation of LAL from the horseshoe crab. Endotoxin detection is more specific with the recombinant Factor C assay because there is less interference from other substances, like beta (β)-glucans. In addition, recombinant Factor C assays are less variable, as compared to the LAL test which may perform differently based on pooling of various lysates, while still providing the sensitivity end-users require.

What new challenges will be faced in the years to come?

JD: The development of new pharmaceutical drug products is becoming more and more sophisticated. These newer products, including biologics providing highly targeted therapies, involve spectacularly expensive production processes. Our challenge is to provide customers with all of the tools necessary to detect and, thereby, mitigate gram-negative bacterial contamination. These efforts require rapid methods, robust LAL testing methodologies, and the means to track and trend in-process and final-product endotoxin testing. Regulatory bodies currently emphasize process understanding, capability and control. These crucial production characteristics will become even more critical in the years to come.

TS: I think that recombinant lysates will become more commonplace, given some concerns about horseshow crab ecology. I also think that innovations will be made with rapid methods, and applied applications like on-line testing of water systems with fixed endotoxin reading devices. It is possible that robotic LAL testing – a fully automated method – will emerge (this was discussed a few years ago but it didn’t really develop). It is possible that the Monocyte Activation Test will challenge LAL as a key test for pyrogens, although adoption of this method has been slow and there are some concerns about its variability. Whatever happens in the future, the need to carry out endotoxin testing will remain as a key release test for many pharmaceutical products.

LW: New pharmaceutical and medical devices are continually being developed and released into commerce after regulatory approval. While some are approved, many more go through the same development process and clinical trials and are not approved. However, all of these products require BET testing if they are parenterally administered or implantable medical devices. Given the recent and expected future increased demand for LAL, the need to develop a sustainable alternative to the LAL method is a growing concern for end-users and regulators.

The distribution of horseshoe crabs is not worldwide. Since the population is limited by a lack of geographical distribution as well as the size of the population, any environmental threat provides a risk to the supply of available HSC. Given the demands being put on the limited HSC resource, as well as the risks to that resource, other options must be explored to meet the demands of the Pharmaceutical and Medical Device industries, and ultimately of the patients that rely on a safe supply of those products.Posted by Dr. Tim SandleContinued growth in the number of tests performed annually and increasing restrictions on fishing quotas for horseshoe crabs are mutually incompatible. The Asian species of horseshoe crabs, TAL, are now reported to be depleted, while the population of LAL on the East Coast of the US also had a significant decline in the 1980s and 1990s.

Tuesday, 14 November 2017

FDA approves first ever ‘digital pill’



An innovative medical device, in the form of a pill containing a built-in sensor has been developed and been given approval, based on safety and efficacy data, by U.S. authorities.

by Tim Sandle

What is being heralded as the world’s first ‘digital’ pill has gained approved by the U.S. Food and Drug Administration (FDA). The pill is called Abilify MyCite. The pill contains a medication called aripiprazole, which treats conditions like schizophrenia, bipolar disorder and depression. Also combined with the pill is an ingestible sensor. The pill comes after several years of research and is a venture between the Japanese pharmaceutical company Otsuka and digital medicine service Proteus Digital Health.

It is the sensor that creates the ‘digital’ or ‘smart’ pill. The purpose of the sensor, according to The Verge, is to record when the pill has been taken. This happens by a signal being sent to a wearable patch (fixed to the left rib cage); and then from the patch to a mobile device such as a smartphone via Bluetooth. The patch has additional functionality. It records activity levels, sleeping patterns, steps taken, and heart rate. The patch needs to be replaced every seven days.

The purpose of this is to determine when a pill has been taken. This either acts as a reminder  to patients that they have (or to verify that they have not) taken their required dose of medication; or, for more serious cases where a patient has been sectioned as the result of a mental disorder, to enable medics to record the fact that a medication has been taken.
Failure to take medications has societal and economic consequences, such as putting a strain on the hospital system. According to Dr. William Shrank, chief medical officer of the health plan division at the University of Pittsburgh Medical Center, who spoke with the New York Times on this subject: “When patients don’t adhere to lifestyle or medications that are prescribed for them, there are really substantive consequences that are bad for the patient and very costly.”


The sensor is only the size of a grain of sand. It is manufactured from silicon, copper, and magnesium. In terms of how the sensor works, an electrical signal is activated when the sensor comes into contact with stomach acid.

It is a common problem with medications, either through forgetfulness or as a conscious act, when patients do not taken the medicines prescribed to them. The digital pill aims to redress this.

Commenting on the go-ahead for the digital pill to be marketed, Mitchell Mathis, who is the director of the Division of Psychiatry Products in the FDA, told PharmaPhorum: “Being able to track ingestion of medications prescribed for mental illness may be useful for some patients.”

The regulator added: “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”


The agreement relates to both parts of the smart medication: Abilify and Proteus Health’s sensor and patch, for the U.S. market. A label warning will accompany the product. This will state that the combined smart system has not been shown to improve patient compliance and that there are concerns about the effectiveness of the tracker in real-time since detection may be delayed. Nevertheless, the digital pill is likely to become popular with the medical establishment. The price of the pill has yet to be announced.


The Wall Street Journal opines that there could now be a raft of approval requests for other digital pills. The paper also notes that the FDA are preparing to hire more staff with understanding of software development in relation to medical devices.

How Staph Cells Dodge the Body’s Immune System


For years, medical investigators have tried and failed to develop vaccines for a type of staph bacteria  associated with the deadly superbug MRSA. But a new study by Cedars-Sinai investigators shows how staph cells evade the body’s immune system, offering a clearer picture of how a successful vaccine would work.

Staph frequently causes skin infections but occasionally can lead to deadly conditions such as sepsis, pneumonia and bloodstream infections, particularly in hospitalized patients whose immune systems could be weakened by illness.

One strain of the bacterium, the superbug methicillin-resistant Staphylococcus aureus (MRSA), is considered one of the top drug-resistant threats in the U.S., causing more than 11,000 deaths per year, according to the Centers for Disease Control and Prevention. In fact, the superbug kills more Americans than HIV.

“Widespread MRSA infections have prompted routine use of once last-line antibiotics, and this is making the antibiotic resistance problem worse,” said George Liu, MD, PhD, co-lead author of the study and a pediatric infectious diseases physician at Cedars-Sinai’s Maxine Dunitz Children’s Health Center and the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. “Our study focuses on why MRSA is so common and why we never develop immunity to these bacteria.”

The study, published in the peer-reviewed journal Cell Host & Microbe, also sheds light on how investigators could develop an effective vaccine against staph.

When exposed to a pathogen like a staph bacterium, the body usually fights it and then forms a memory of how its immune system responded. The next time the body encounters the same pathogen, it can use that memory to fight off the microbe much more easily.

But the body can suffer from repeated staph infections throughout life without developing a robust protective memory immune response. The study shows that staph bacteria are able to dodge this immune response.  

When the staph cell wall primarily is kept intact after infecting a host, bacterial molecules don’t escape the staph cell and the body isn’t prompted to produce robust protective immune memory.
“Essentially, staph tricks the body’s T cells, which are white blood cells that fight infection, and prevents them from mounting an effective defense,” said co-lead author Gislaine Martins, PhD, an assistant professor at the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and departments of Biomedical Science and Medicine.

As a result, the body does not develop long-term immunity and remains vulnerable to that particular staph infection throughout life. While certain staph bacteria cause mild skin infections, other strains of staph bacteria can wreak havoc in the bloodstream and bones, sometimes leading to amputations. 
“The study explains why our immune system is fooled by staph,” Martins said. “Staph evolved to have this enzyme that makes this modification in its cell wall. This modification protects the wall from degradation and therefore from being properly detected by the immune system, which won’t remember the bacteria the next time the body is infected.”

When study authors removed the cell wall modification, the staph cells spilled their molecules more easily. The modified bacteria sparked a robust memory immune response that  protected against reinfection. 

The study provides clues about what type of element could be added to staph vaccines to make them more effective. Whereas most staph vaccines have tried to stimulate antibodies — specialized molecules that recognize foreign bodies and help to mobilize the immune system — this study suggests that a successful vaccine should harness the body’s T cells.

DOI: 10.1016/j.chom.2017.08.008

Posted by Dr. Tim Sandle

Monday, 13 November 2017

Antimicrobial copper surfaces in hospitals



Infection control in hospitals is of paramount importance in order to reduce the potential for healthcare associated infections (an infection whose development is favored by a healthcare environment.) Infection control is concerned with eliminating as many pathogenic microorganisms as possible and limiting their transfer. This covers a range of measures from handwashing, disinfection, selection of antimicrobial drugs, the treatment of surfaces and so on. With surfaces, many types of microorganisms can persist for extended periods of time (some organisms can survive for longer than thirty days on standard surfaces); consequently touch-surfaces represent risk spots for pathogen transmission. In the hospital setting, some types of key equipment can be manufactured with antimicrobial touch components with the aim of making the surfaces self-disinfecting. For this a recent trend in the hospital setting has been to revisit the inherent antimicrobial properties of certain metals. A prominent example is the use, or incorporation of, copper.

Tim Sandle has written a review of the application of copper in hospitals. The reference is:

Sandle, T. (2017) Antimicrobial copper surfaces in hospitals, The Clinical Services Journal, 16 (6): 47-51

For a copy, please contact Tim Sandle.

Posted by Dr. Tim Sandle

Sunday, 12 November 2017

Millions of new genes in human microbiome


A new study of the human microbiome has uncovered millions of previously unknown genes from microbial communities in the human gut, skin, mouth, and vaginal microbiome, allowing for new insights into the role these microbes play in human health and disease.

The study, from researchers at the University of Maryland School of Medicine (UM SOM), Harvard T.H. Chan School of Public Health, the Broad Institute of MIT and Harvard, and the University of California San Diego, triples the amount of data previously analyzed in this project, and is the largest human microbiome study ever.

The results are a significant jump in the amount of information available to scientists. This publication provides new insight into the changes in our microbiome over time and could lead to a greater understanding of the genetic differences that are unique to an individual's microbes.

This study is part of the National Institutes of Health Human Microbiome Project, launched in 2008 to identify and characterize human microbes, explore microbes' relationship to health and disease, and develop computational tools to analyze the microbes. The microbiome has been linked to various aspects of human health including the robustness of our immune system and our susceptibility to chronic illnesses such as Crohn's disease and cancer.

In the new study, the researchers analyzed an additional 1,635 new microbiome samples, for a total of 2,355 sampled from 265 people over time. The scientists used DNA sequence analysis tools to identify which organisms are present in various body sites, determine whether they change or stay relatively stable over time, and explore their function. This study also provides one of the largest profiles of non-bacterial members -- viruses and fungi -- of the microbiome. In addition, it unraveled some of the biochemical activity that allows microbes to play a role in human health.

See:

Jason Lloyd-Price, Anup Mahurkar, Gholamali Rahnavard, Jonathan Crabtree, Joshua Orvis, A. Brantley Hall, Arthur Brady, Heather H. Creasy, Carrie McCracken, Michelle G. Giglio, Daniel McDonald, Eric A. Franzosa, Rob Knight, Owen White, Curtis Huttenhower. Strains, functions and dynamics in the expanded Human Microbiome ProjectNature, 2017; DOI: 10.1038/nature23889

Posted by Dr. Tim Sandle

Saturday, 11 November 2017

Imagining a world without species


Categorizing species can get especially hazy at small, microbial scales. After all, the classical definition of species as interbreeding individuals with sexually viable offspring doesn't apply to asexual organisms. Examining shared DNA doesn't help either: collectively, E. coli bacteria have only 20 percent of genes in common. The classification process gets even trickier as many microbes work so closely that it is unclear what to call separate organisms, let alone separate species.

The woes of classification generate contentious debates in the biology community. But, for postdoctoral fellow Mikhail Tikhonov, one field's contentious debate is another's theoretical playground. In new research, he asks: Could organism interactions be described without mentioning species at all?

Key question: “how does evolution act on the structure within a community, rather than on a species?"

This question is not only interesting on a theoretical level, but could have real-world implications in understanding and treating human disease. While some diseases (like pneumonia or meningitis) have specific culprits, many others (like obesity or type II diabetes) seem to be associated to a community-level dysfunction of our microbiome -- the highly diverse bacterial communities that live on and inside our bodies. To understand these diseases, researchers must understand how the system works as a whole.

See:

Mikhail Tikhonov. Theoretical microbial ecology without speciesPhysical Review E, 2017; 96 (3) DOI: 10.1103/PhysRevE.96.032410

 Posted by Dr. Tim Sandle

Friday, 10 November 2017

Aggressive UTI bacteria hijack copper


Escherichia coli bacteria -- those at the root of hard-to-treat urinary tract infections (UTIs) -- hijack trace amounts of copper in the body and use it as a nutrient to fuel growth. This finding suggests blocking this system may starve E. coli infections, opening the door to treating UTIs using drugs that work differently from traditional antibiotics.

Copper is an essential mineral -- found in shellfish, whole grains, nuts, beans and other foods. It can kill pathogens in high concentrations. But it was unclear how E. coli handles copper ions present in urine, an extremely complex medium containing many trace metals and other compounds.

In past work studying strains of E. coli known to cause difficult-to-treat UTIs, the researchers showed that a molecule called yersiniabactin that is secreted by the bacteria sequesters copper, preventing it from accumulating to antibacterial levels. But what it does with this bound copper has been unknown.

While bacteria are known to bring iron -- another essential mineral -- into the cell, the researchers noted that E. coli have long been thought to lack a method to import copper. Indeed, scientists have assumed that yersiniabactin only imports iron.

In the new study, the researchers showed that yersiniabactin imports copper ions into the cell, where these charged particles help trigger the many biochemical reactions that bacteria require to grow and reproduce. The scientists further showed that once relieved of its mineral cargo, yersiniabactin goes back outside the cell to mop up more copper. The researchers dubbed this strategy "nutritional passivation." In metallurgy, passivation refers to treating or coating metal to make it less reactive.

The researchers also have shown that yersiniabactin can bind to a variety of metals beyond copper and iron, including nickel, cobalt and chromium.

See:

Eun-Ik Koh, Anne E Robinson, Nilantha Bandara, Buck E Rogers, Jeffrey P Henderson. Copper import in Escherichia coli by the yersiniabactin metallophore systemNature Chemical Biology, 2017; DOI: 10.1038/nchembio.2441

Posted by Dr. Tim Sandle

Thursday, 9 November 2017

Antibiotic Alternative Micreos wins Most Impactful Innovation


In the presence of former UN-Secretary-General Kofi Annan and Dutch minister Melanie Schultz of Infrastructure & the Environment, Micreos' alternative to antibiotics was chosen as the most impactful innovation of The Netherlands. Micreos will represent The Netherlands at the semi-finals of Ideas from Europe in Talinn, Estonia on November 22 2017.

Micreos' endolysin technology, enabling targeted killing of only unwanted bacteria - regardless of antibiotic resistance - was selected by a professional jury. Jury-chair Kasja Ollongren, Deputy mayor of Amsterdam, emphasized the impact Micreos' products can have for millions of people.


The Making Waves-conference was attended by hundreds of policy makers, entrepreneurs, investors and developers. Guest of honour, Kofi Annan, winner of the Nobel Peace Prize, said: "I am really excited about Micreos' alternative to antibiotics".


Kasja Ollongren: "We chose Micreos because the company's technology is already helping tens of thousands of people and we're convinced Micreos' alternative to antibiotics can be life-changing for millions."

Micreos CEO Mark Offerhaus: "Antibiotic-resistance is an enormous global problem. We are honoured with the recognition. Gladskin has already been life-changing for people suffering from inflammatory skin diseases such as eczema, acne, rosacea and wound infections caused or aggravated by the Staphylococcus aureus bacteria, including the resistant MRSA. But as far as we're concerned, this marks only the beginning. Our endolysin technology offers a real and sustainable alternative to antibiotics, the broad potential of this technology is immeasurable. There's no need to wait and no time to lose."

Posted by Dr. Tim Sandle

Wednesday, 8 November 2017

Ensuring Product Safety & Effectiveness

The Role of Pharmaceutical Quality Assurance in Ensuring Product Safety & Effectiveness

Quality Assurance – A Systematic Approach to Overcoming the Surge of Substandard Medical Products by Edward Simpson


Quality assurance entails all the arrangements made to ensure that pharmaceutical products are safe, effective and have the desired quality according to their intended use. Quality assurance is considered a good manufacturing practice for meeting the standards and specifications of pharmaceutical products in terms of quality, reliability, efficacy and safety. To ensure the safety of public health, standard operating procedures are designed in compliance with scientific regulations and executing the SOPs is the responsibility of the QC department.

Calibration services play a vital role in various aspects of quality assurance right from manufacturing of medical devices to ensuring adherence to product releases. Calibration services ensure compliance with pharmaceutical quality standards for patient safety.

Ensuring Quality on the Floor

The quality assurance unit of highly specialized organizations is responsible for delegating the operations to quality employees who must ensure that the law is complied to and the end-users are protected from the potential accidental defects in the manufacturing process. Every pharmaceutical company knows the risks involved in the mass manufacturing of products for patient use but not many are aware of how to combat these hazards efficiently. Calibration services reduce the risk and improve product safety.

Today medical device manufacturing practices are governed by FDA and ISO and more and more companies are accustomed to the impact of instrument calibration on product liability. This has compelled companies to follow safety oriented procedures and reduce the risks associated with product liability.

Steps Involved in Quality Assurance

Quality assurance is a broad concept that encompasses monitoring and management of production processes, documenting, and analyzing data to maintain product quality
  • QA starts with consulting the program advisor and the technical crew on developing and designing QA measures to fulfill the standards mandated by the regulatory authorities.
  •  Locating calibration services to perform the required external checks Evaluating in-house resources and capabilities to identify the limitations
  • Making recommendations for process improvements that can be implemented over time

The Solution

Professional organizations need to actively cultivate a culture where quality management is the core focus. For this, organizations need to develop a robust training program that efficiently addresses quality management issues and covers technical documentation and reporting obligations for timely investigation of quality issues. Internal and external checks should be performed by quality employees and field technicians at the project sites.

Internal Checks should include the Following Verifications:

  •          The use of de-ionized water for identifying contamination
  •          Filtering of buffered water used for testing results in positive and negative plates
  •          Field duplicates are collected at the same time and at the same place for sampling precision 
  •         Samples are segregated into subsamples before they can be analyzed for precise comparison
  •          The instrument is set to zero using de-ionized water and blanks are employed to check for         drifts.
  •         Instruments are calibrated against multiple standard concentrations of a specific indicator

External checks should be performed by a licensed QC lab while ensuring that:

  •          The duplicated sample collected at the site is analyzed at the same time and at the same place by an independent sampler.
  •         One sample is analyzed by both the project lab and the independent lab and both the results are compared for discrepancies.
  •          All the field duplicates are sent to an independent lab and the results are duly compared with the measurements.
  •          All the labeled samples with known concentrations are sent to the QC lab for analysis before the first run is performed and the results are compared for discrepancies.
  •          For unknown samples, the findings should be compared with known values by an independent QC lab and any discrepancies should be reported.
Pharmaceutical companies that ignore these quality checks are likely to suffer serious consequences. Focusing on compliance is not enough to succeed, companies need calibration services to make sound decisions regarding product quality.

 Quality Assurance V/s Compliance  

While industries have a singular focus on quality, regulatory authorities concentrate on compliance. Both the terms are used interchangeably but there is a considerable difference between the two. Quality assurance entails all the processes and procedures implemented in an organization to ensure high-quality standards that meet regulatory requirements while compliance is a function that simply documents the quality of your manufacturing processes and products. It is possible to ensure quality even without compliance checks but there can be no compliance in the absence of quality. Compliance treats the symptoms of a problem but quality treats the cause itself.

Author Bio: Edward Simpson works for RS Calibration Services and has a knack for finding faults in machines and does not rest until they are rectified to perfection. He lives in Pleasanton, CA and loves to write about how machines work and about the importance of proper care and calibration of equipment. When he's not working or writing, he loves to run to stay fit.