Sunday 30 July 2017

Battling infections with bioelectricity

Is the answer to fighting pathogens connected with bioelectricity? Promising new research suggest this is possible by using drugs to changing electrical charge of cells. Studies have been performed in frogs.
What is remarkable about the studies is the fact they have used existing medications. The drugs, which are approved for use in humans, were used to eliminate an Escherichia coli infection in frogs. The action of the drugs triggered a reversal of the electrical charge in the cells of the frigs, wiping out the pathogen.

For the study drugs that either depolarize (positively charge) or hyperpolarize (negatively charge) cells were tested. It was found that the negative charge effect is of significance. The drug that achieved this in an optimal way was one called ivermectin. Ivermectin is a medication effective against many types of parasites, such as head lice, scabies, river blindness, strongyloidiasis, and lymphatic filariasis.
Wiping out bacteria
Analyzing what's happening, Tufts University biologists discovered that administering specific drugs leads to the interior of cells becoming more negatively charged. In tadpoles (of the frog Xenopus laevis), this strengthened the innate immune response to E. coli infection and injury. Hence the researchers have found a hitherto unknown and novel aspect of the immune system. This has been termed "regulation by non-neural bioelectricity." The finding could be significant, possibly opening up a new approach for clinical applications of the technique in human medicine.

As the lead researcher, Dr. Michael Levin explains: "All cells, not just nerve cells, naturally generate and receive electrical signals." He adds that by "being able to regulate such non-neural bioelectricity with the many ion channel and neurotransmitter drugs that are already human-approved gives us an amazing new toolkit to augment the immune system's ability to resist infections."
Bioelectricity refers to electric potentials and currents produced by or occurring within living organisms. These potential vary between one to a few hundred millivolts. Perhaps the best known example is with the electric eel.
Such electric fish produce their electrical fields from a specialized structure called an electric organ. This is made up of modified muscle or nerve cells, which became specialized for producing bioelectric fields stronger than those that normal nerves or muscles produce.
The pathogen killing effect also rests with the immune system. All vertebrates possess two kinds of immunity: the adaptive immune system, which relies on the memory of previous exposure to a specific pathogen; and the innate immune system, which is the first line of defense against pathogens. It is the innate immune system that is being studied in relation to bioelectricity.
Immune system in action
The reason why this is important relates to the role this facet of the immune system plays with tissue repair and regeneration. Also important to the process is the neurotransmitter serotonin, which acts as an intermediary between voltage and immune response. Serotonin is found in all bilateral animals, where it mediates gut movements and the animal's perceptions of resource availability (primarily to food).
The combination of ivermectin and bioelectricity led to the proportion of embryos the bacterial increasing average 32 percent. This was compared tadpoles not given the drug. Here, with the untreated tadpoles, the mortality in untreated rate was 50 to 70 percent.
It is hoped the developed will lead to a new understanding of innate immunity can lead to new developments for fighting pathogens, especially new ones from which there is no adaptive immune system memory. The longer-term aim is to develop a treatment for people by manipulating the bioelectric microenvironment through new combinations of depolarizing drugs. Before doing so a greater understanding is required of how and why bacteria respond to the changes to cell environment and why they find these changes inhospitable and potentially destructive.
At present it is though the electrical variations alter the membrane potentials of the bacterial cell wall
The research has been published in the journal npj Regenerative Medicine, under the title "Bioelectric regulation of innate immune system function in regenerating and intact Xenopus laevis."
In related news, researchers are looking at bioelectric effects further, such as evaluating the antibacterial efficacy of a bioelectric dressing containing silver and zinc against various wound pathogens. With this, the microbial killing is possibly enhanced first by bioelectric field attracted microbes carrying a negative charge to the positive pole containing silver and zinc.

Posted by Dr. Tim Sandle

Sunday 23 July 2017

New antibiotic effective against drug-resistant bacteria

Scientists have discovered a new antibiotic effective against drug-resistant bacteria: pseudouridimycin. The new antibiotic is produced by a microbe found in a soil sample collected in Italy and was discovered by screening microbes from soil samples. The new antibiotic kills a broad spectrum of drug-sensitive and drug-resistant bacteria in a test tube and cures bacterial infections in mice.

Pseudouridimycin inhibits bacterial RNA polymerase, the enzyme responsible for bacterial RNA synthesis, through a binding site and mechanism that differ from those of rifampin, a currently used antibacterial drug that inhibits the enzyme. Because pseudouridimycin inhibits through a different binding site and mechanism than rifampin, pseudouridimycin exhibits no cross-resistance with rifampin, functions additively when co-administered by rifampin and, most important, has a spontaneous resistance rate that is just one-tenth the spontaneous resistance rate of rifampin.

Pseudouridimycin functions as a nucleoside-analog inhibitor of bacterial RNA polymerase, meaning that it mimics a nucleoside-triphosphate (NTP), the chemical "building block" that bacterial RNA polymerase uses to synthesize RNA. The new antibiotic binds tightly to the NTP binding site on bacterial RNA polymerase and, by occupying the NTP binding site, prevents NTPs from binding.

Pseudouridimycin is the first nucleoside-analog inhibitor that selectively inhibits bacterial RNA polymerase but not human RNA polymerases.


Sonia I. Maffioli, Yu Zhang, David Degen, Thomas Carzaniga, Giancarlo Del Gatto, Stefania Serina, Paolo Monciardini, Carlo Mazzetti, Paola Guglierame, Gianpaolo Candiani, Alina Iulia Chiriac, Giuseppe Facchetti, Petra Kaltofen, Hans-Georg Sahl, Gianni Dehò, Stefano Donadio, Richard H. Ebright. Antibacterial Nucleoside-Analog Inhibitor of Bacterial RNA Polymerase. Cell, 2017; 169 (7): 1240 DOI: 10.1016/j.cell.2017.05.042

Posted by Dr. Tim Sandle

Friday 21 July 2017

New health and safety standard

A new International Standard due out early next year – ISO 45001. This is ISO’s first standard for occupational health and safety management systems.

According to ISO: “ISO 45001, Occupational health and safety management systems – Requirements with guidance for use, will provide the requirements for implementing a management system and framework that reduces the risk of harm and ill health to employees.

The standard is being developed by a committee of occupational health and safety experts and will follow in the footsteps of ISO’s other management systems approaches, such as ISO 14001 (environment) and ISO 9001 (quality). It will take into account other International Standards in this area including OHSAS 18001, the International Labour Organization’s ILO-OSH Guidelines, various national standards and the ILO’s international labour standards and conventions.”

For further details see: ISO

Posted by Dr. Tim Sandle

Thursday 20 July 2017

European Pharmacopoeia revises Biological Indicator Chapter

The general chapter in the European Pharmacopoeia (5.1.2) relating to biological indicators has undergone a significant revision. The new version has been issued with the release of supplement 9.2 to the 9th edition of the pharmacopoeia (1). The changes to the chapter are signaled by the revision to the title, which now becomes “Biological indicators and related microbial preparations used in the manufacture of sterile products”. Previously the chapter was headed “Biological indicators of sterilization.” The change of title reflects the adaption of the chapter to take into account microbial preparations used for sterilization grade filtration. This article assesses the key changes.

The reference is:

Sandle, T. (2017) European Pharmacopoeia revises Biological Indicator Chapter, GMP Review, 16 (1): 4-6

For a copy, please contact Tim Sandle

Posted by Dr. Tim Sandle

Wednesday 19 July 2017

What's that smell?

Did you know that bacteria make us humans and other animals smell the way we do? On top of that, animals use that smell to communicate with each other.

The “fermentation hypothesis of chemical recognition” says that bacteria in the scent glands of mammals generate metabolites with specific odors that animals use to communicate with each other. What’s more, this hypothesis explains how variations in these chemical signals are actually due to variations in those populations of bacteria.

News from Laboratory Roots:

Let’s start with humans, Corynebacterium is responsible for that distinct “body odor” that emanates from our armpits. That odor is caused by 3-methyl-2-hexenoic acid (3M2H) and 3-hydroxy-3-methylhexanoic acid (HMHA). It turns out that the precursors for these chemicals are cleaved by a zinc-dependent bacterial aminoacylase.

In one study, researchers isolated bacteria from the human axilla. They identified 19 strains of Corynebacterium and 25 strains of Staphylococcus. Curiously, only isolates of Corynebacterium, not Staphylococcus, produced 3M2H or HMHA from the precursors 3M2H-Gln or HMHA-Gln, indicating that these strains produced an Nα-acylglutamine aminoacylase.

So, what’s the use of human body odor? It’s safe to say that most people think body odor smells bad - it’s definitely not attractive to other humans. Some researchers think that may be the point - or at least it was at some point in our evolution. Body odor may have been used by early humans as a way to assert dominance or repel rivals.

One of these odor chemicals is trimethylamine, which is specific for the olfactory receptor TAAR5. Trimethylamine synthesis requires two steps, one of which involves bacteria. We’ve all smelled trimethylamine before, it’s the stinky smell of bad breath and spoiled food!

In humans, trimethylamine is the byproduct of bacteria metabolizing dietary choline, and researchers wanted to know if the same held true for mice. To figure things out, they collected urine from mice that were fed a choline/methionine-free diet or that were treated with an antibiotic. Sure enough, these mice produced less trimethylamine in their urine than control mice.

Likewise, urine from wild type mice contained trimethylamine that activated its receptor TAAR5 (assayed with a reporter gene), but urine from mice on the choline-free diet or treated with antibiotics did not activate TAAR5. These findings suggest that bacteria produce trimethylamine from dietary choline.

While trimethylamine is produced by commensal bacteria, pathogens produce their own array of odors. Mice have receptors in their vomeronasal organ that recognize formylated peptides that are produced by tissue damage or bacterial infection. There are also chemosensory cells in the respiratory epithelium that detect bacterial quorum sensing molecules called acyl-homoserine lactones.

Next are the meerkats. These members of the mongoose family are native to South Africa. They produce a smelly paste from a pouch beneath their tails. They use this paste to mark their territories, applying it to plants, rocks, and their meerkat pals. Researchers found over 1,000 types of bacteria and some 220 odorous chemicals in the stinky paste. The key finding was that specific odors are produced by specific microbial communities - a specific meerkat family smells the way it does because of its own specific microbes.

The group detected five main phyla of bacteria in the meerkats’ anal pouch - Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria. Specific genera of bacteria found in the paste were Porphyromonas, Fusobacterium, Anaerococcus, and Campylobacter.

The researchers also found that subordinate and dominant male meerkats had different bacterial communities in their pouches. However, there were no significant differences among dominant and subordinate females.

Finally, like meerkats, hyenas, deposit a scented paste from anal scent pouches to communicate with other hyenas. In one study, researchers used scanning electron microscopy to look for bacteria in the scent pouches of both spotted and striped hyenas (two groups that differ rather significantly in their lifestyles and behavior).

They found that the bacterial communities differed between spotted and striped hyenas, but all communities were largely made up of fermentative anaerobes - specifically, species from the order Clostridiales. For the spotted hyenas, they identified Clostridiales from the genera Anaerococcus, Clostridium, Fastidiosipila, Finegoldia, Murdochiella, Peptoniphilus, and Tissierella. The bacterial communities differed, however, based on sex and female reproductive status.

Monday 17 July 2017

Pathological appendix versus normal appendix

Antonella Chesca and Tim Sandle have written a paper of interest to those working in pathology or medicine. It concerns the pathological appendix compared with the normal appendix.

Here is the abstract:

This article makes reference to certain structural issues, that can be found during the appendix surgery and which are examined microscopically. For the study permanent preparations resulting from appendectomies, charged for removal in cases of gangrenosum appendicitis, were examined microscopically. For comparison and analytically, describable microscopic permanent preparations with gangrenosum appendix, were compared with normal appendix. Stains used in this structural study are Hematoxylin-Eosin, van Gieson and Gomori silver impregnation. Preparations were examined using Nikon microscope and magnifying lenses with powers x10, x20 and x40.

The reference is:

Chesca, A. and Sandle, T. (2017) A new approach related to structural aspects of pathological appendix versus normal appendix, Medicine and Ecology, 82 (1): 115-118

The article can be accessed here.

Posted by Dr. Tim Sandle

Sunday 16 July 2017

Quality Risk Management for Manufacturing Systems

PDA has issued a new technical report of interest. The title is “•      PDA Technical Report No. 54-5 (TR 54-5) Quality Risk Management for the Design, Qualification, and Operation of Manufacturing Systems.”

“This technical report provides a practical guide on how to manage quality risks throughout the manufacturing system lifecycle and illustrates concepts through two case studies, thereby bridging the gap.”

For details see: PDA

Posted by Dr. Tim Sandle

Friday 14 July 2017

Fungi assess radioactivity in soil

The Environmental Radioactivity Laboratory of the UEx has carried out a study to quantify radioactive presence in fungi. According to the research, this quantification is made using transfer coefficients that compare the radioactive content in the receptor compartment (fungi) of the radioactive contamination, to that existing in the transmitter compartment (soil). From the study, we may conclude that fungi can be used when assessing the presence or absence of radioactive contamination in the soil.

The Environmental Radioactivity Laboratory of the University of Extremadura (LARUEX) has carried out a study to quantify radioactive presence in this foodstuff. Thus, the author of the study, Javier Guillén, explains that "this quantification is made using transfer coefficients that compare the radioactive content in the receptor compartment of the radioactive contamination, that is to say in the fungi, to that existing in the transmitter compartment, which in this case would be the soil."To conduct this research the authors considered the base level of radionuclides established in ecosystems with low radioactive content like our region, and then used the software called the ERICA Tool which, as the researcher explains, "allows one to enter the transfer coefficient from the soil to the organism -- in this case the fungus -- thus calculating the dose of radionuclides a non-human organism receives."

From the study, we may conclude that the estimated dose rates for fungi in Spain are similar to those determined for other animals (animals and plants) and therefore this species can be used when assessing the presence or absence of radioactive contamination in the soil, as a result of which, as the researcher asserts, "even though it is not strictly necessary to include fungi amongst the existing instruments and frameworks of assessment, they can be used in ecosystems which may require them, based on criteria such as biodiversity."

Moreover, in the case of the fungi analysed, which are concentrated in the Mediterranean area, we should also highlight the fact that they do not contain a high dose of radionuclides, meaning there is no environmental contamination and they are therefore perfectly suitable for consumption by humans.


J. Guillén, A. Baeza, N.A. Beresford, M.D. Wood. Do fungi need to be included within environmental radiation protection assessment models? Journal of Environmental Radioactivity, 2017; 175-176: 70 DOI: 10.1016/j.jenvrad.2017.04.014

Posted by Dr. Tim Sandle

Monday 10 July 2017

Structural aspects of tonsillitis

Antonella Chesca and Tim Sandle have produced a new paper of interest in relation to medicine, focusing on tonsillitis. The abstract reads:

The present study shows structural issues relating to various forms of tonsillitis, frequently encountered in clinical practice. For the study, it was observed and analyzed with light microscopy, permanent preparations made by processing samples taken from intraoperative fragments. It is useful to undertake microscopic examination of samples in order to help establish accurate pathologic diagnosis.

The reference is:

Chesca, A. and Sandle, T. (2017) Structural aspects of tonsillitis, Medicine and Ecology, 82 (1): 112-114 

The paper can be accessed here.

Posted by Dr. Tim Sandle

Saturday 8 July 2017

Why antibiotics fail

When a patient is prescribed the wrong antibiotic to treat a bacterial infection, it's not necessarily the physician who is at fault. The current antibiotic assay -- standardized in 1961 by the World Health Organization and used worldwide -- is potentially flawed.

So says UC Santa Barbara biologist Michael Mahan, whose lab has developed a new antimicrobial susceptibility test that could transform the way antibiotics are developed, tested and prescribed.

The standard test specifies how well drugs kill bacteria on petri plates containing Mueller-Hinton Broth, a nutrient-rich laboratory medium that fails to reproduce most aspects of a natural infection. Now, Mahan and colleagues have used a mouse model to demonstrate that a variety of antibiotics work differently against various pathogens when inside the mammalian body. Their findings appear in the journal EBioMedicine.

"The message is simple: Physicians may be relying on the wrong test for identifying antibiotics to treat infections," said Mahan, a professor in UCSB's Department of Molecular, Cellular and Developmental Biology. "By developing a test that mimics conditions in the body, we have identified antibiotics that effectively treat infections caused by diverse bacteria, including MRSA, the cause of deadly Staphylococcal infections. These drugs have been overlooked because they failed the standard tests, despite being inexpensive, nontoxic and available at local pharmacies."

The research has significant implications for public health. If a drug that passed the standard test doesn't work, physicians can now choose a different drug immediately rather than increase the dose of the same drug when patients return -- often in worse condition -- after an ineffective first course of treatment.

Reliance on the standard test may have contributed to the rise in multidrug-resistant bacteria, Mahan noted, due to the continued prescription of ineffective antibiotics. Further, he added, the standard test may also be slowing the discovery of new antibiotics. "These 'wonder drugs' may already exist but have been rejected by the standard test and are consequently not used in practice," Mahan said.

The scientists also report a way to "fix" the standard test to better predict how well antibiotics will treat infections: Simply add sodium bicarbonate. More commonly known as baking soda, this chemical is found in abundance in the body, where it helps to maintain precise blood pH. "Sodium bicarbonate makes the petri plates behave more like the body and increases the test's accuracy for assigning the appropriate antibiotic to treat infections," explained co-lead author Douglas Heithoff, a project scientist at UCSB's Center for Nanomedicine.

Mahan also points out that pharmaceutical companies could benefit from using the revised test to rescreen their collections of purified compounds that have failed the standard test. "There could be a treasure trove of compounds that have been shelved but could actually be quite effective against antibiotic-resistant strains," he said.

"Things aren't as gloomy as we thought," Mahan added. "We just have to be smart about it and change the way we're using the drugs we already have while we continue to search for new ones."


Selvi C. Ersoy, Douglas M. Heithoff, Lucien Barnes, Geneva K. Tripp, John K. House, Jamey D. Marth, Jeffrey W. Smith, Michael J. Mahan. Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing. EBioMedicine, 2017; DOI: 10.1016/j.ebiom.2017.05.026

Posted by Dr. Tim Sandle

Thursday 6 July 2017


News from the USP Pharmacopeial Forum:

Chapter 1231 “Water for Pharmaceutical Purposes” (Revision proposal target, USP41-NF36 1st Supplement)

Proposed revisions are as follows:
  • Add information to the section on Sampling for microbial and chemical considerations intended to provide more clarification and guidance on sample hold times.
  • Include some modifications to terminology in the Microbial Evaluations section.
  • Provide clarification under Chemical Evaluations regarding compliance with elemental impurities requirements.

Posted by Dr. Tim Sandle

Tuesday 4 July 2017

Predatory bacteria kills multi-drug resistant bacteria on eyes

Scientists have developed a new method to clear antibiotic resistant bacteria from the surface of the eye -- introducing a new strain of bacteria that preys on other microorganisms. The research is being presented at the 2017 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) this week in Baltimore, Md.

Experiments on rabbit eyes compared the ability of predatory bacteria and vancomycin, an antibiotic, to treat an infection of multi-drug resistant P. aeruginosa. The predatory bacteria proved superior to vancomycin in terms of time-to-bacterial clearing, wound healing inhibition and toxicity. The researchers noted a remarkable inhibition of wound healing by vancomycin, whereas predatory bacteria did not alter wound healing.

The increasing spread of antibiotic resistant microorganisms is a global health problem. Multi-drug resistant P. aeruginosa, which is spread by contact with a contaminated surface or water, can cause severe illness and death in people in the hospital and/or with weakened immune systems. It can cause eye infections in healthy people using extended-wear contact lenses. Vancomycin is used to treat MRSA infections.

Posted by Dr. Tim Sandle

Monday 3 July 2017

Tim Sandle Q&A

Tim Sandle has been interviewed by the Institute of Validation Technology as part of the ‘Meet the Board’ series (Dr Sandle is a regular contributor to the IVT Network).

Here is an extract:

What is your advice to people who want to begin publishing their work but are maybe a little too hesitant to start?

The trick is to start off with something small. The best approach depends on the field and subject matter. With pharmaceuticals and healthcare, writing on a new standard that has been published or describing a new method are good places to start, trying to sum up what the change is about. Much of it is similar to writing an essay at school: introduction, main section, and conclusion. In the introduction say what the article is about; the middle section discuss the subject (for a newish writer limiting this to three main points is a good way of structuring the body of the article); and then summarize at the end. And then proof read.

The subject needs to be something you’re interested in and you need to enjoy writing. Every style is different (varying from the formal to the informal) and there’s no right or wrong way: if you’ve communicated what you want, then it’s worked. The first article I wrote was about 20 years ago and it was about microbiology on the Internet (which, believe it or not, wasn’t in widespread use at the time!) surveying websites.

The full interview can be read here: IVT

Sunday 2 July 2017

Probing insight into antimicrobial resistant fungus

A major systematic review of the pathogenic fungus Candida auris has been conducted. This yeast-like fungus has been found in hospitals and it is resistant to several classes of antimicrobial drugs. This poses serious risks for those infected.

A new report has looked at the spread of the fungus and the mechanisms by which the organism is resistant to antimicrobial substances. The aim is to find a crack in the fungus’ armor and to find effective ways to eliminate infections. The new research has focused on information relating to C. auris drug resistance and growth patterns. The outcome is that a new drug, still at the trial stage and called SCY-078, might be the best candidate for curing infections.
The fungus was cam to attention in 2009 (where C. auris was isolated from the ear canal of a patient at a hospital in Japan). Since then it has been linked to invasive infections in nine countries, where a big risk is the presence of the fungus on medical devices like catheters. In those infected C. auris can cause what is known as fungemia, yielding candidemia (systemic candidiasis). Fungemia is the presence of fungi in the blood. Symptoms associated with fungemia, including pain, acute confusion, chronic fatigue, and infections. The fungus produces destructive enzymes that help the fungus to establish infections in body tissue.
With the new candidate drug, Professor Mahmoud Ghannoum, who works at Case Western Reserve School of Medicine, said: “This emerging fungal species has started to infect patients globally, causing invasive infections that are associated with a high death rate.”
He adds further: "It is multidrug-resistant, and some strains isolated from patients are resistant to all commercially available antifungal drugs. Multidrug-resistance used to be reported for bacteria only, and now we must add fungi to the list.”
To the study the fungal-drug interaction, Professor Ghannoum’s team looked at 16 strains of C. auris collected from infected patients in Germany, Japan, Korea, and India. These strains were then tested against a battery of 11 drugs. This was to identify suitable classes and drug concentrations that could combat infection. This showed that SCY-078 was the most promising. This drug acts to distort the fungus and impairs its growth, preventing it from dividing. The new finding paves the way for experimental trials using the drug to begin.
The research has been published in the journal Antimicrobial Agents and Chemotherapy. The research paper is titled “The Emerging Candida auris Characterization of Growth Phenotype, Virulence Factors, Antifungal Activity, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation.”

Posted by Dr. Tim Sandle

Saturday 1 July 2017

International Group B Strep Throat Awareness Month

Group B Streptococcus (GBS) is a bacteria that’s naturally found in the digestive and lower reproductive tracts of both men and women. Approximately 1 in 4 pregnant women carry GBS, and the U.S. Centers for Disease Control and Prevention (CDC) states that GBS is the leading cause of sepsis and meningitis in newborns.

Not all babies exposed to GBS become infected. But, for those who do, the results can be devastating. GBS can cause babies to be miscarried, stillborn, born prematurely, become very sick, have lifelong handicaps, or even die.

Fortunately, there are many ways to protect your baby from GBS, as well as prevent its devastating effects on those infected with the disease. The mission of International Group B Strep Throat Awareness Month is to raise awareness/education around both prevention and treatment in the hopes of decreasing the number of babies suffering from GBS.

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