Monday, 24 July 2017

Chronic obstructive pulmonary disease


Antonella Chesca and Tim Sandle have written an article looking at chronic obstructive pulmonary disease.

Here is the abstract:

The present study refers to the exploration of the respiratory function of patients who presented acute symptoms of chronic obstructive pulmonary disease. In the medical specialty units, examination was performed using a standard chest X-ray imaging investigation; followed by a spirometry test, according to the patient's severity of symptoms, using the betamimetics test. Both the X-ray result and the imaging investigation of spirometry showed changes. Changes varied according to the patients from different investigate disease groups in relation to chronic obstructive pulmonary disease.

Here is the reference:

Cheşcă A., Cheşcă S. A., Sandle T. (2016) An approach on chronic obstructive pulmonary disease, Medicine and Ecology, 80 (3): 116-119

The publication can be accessed here.

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.

See:

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

Saturday, 22 July 2017

Bacteria from hot springs solve mystery of metabolism


Combustion is often a rapid process, like fire. How can our cells control the burning process so well? The question has long puzzled researchers. Using bacteria from hot springs, researchers from Stockholm University now have the answer.

Light a match and place it near a candle. You would see a fire and feel the heat when the stearin is burning, while consuming oxygen from air and converting the fuel to carbon dioxide and water. However, when our body burns fat, sugar or protein containing the same amount of energy, we do not vanish into fire and smoke, but use the energy for moving our muscles or for thinking. How does our body control the burning process so well? Researchers at Stockholm University have finally been able to monitor the process and to uncover the mechanism.
"We have shown how oxygen is combusted after it has been transported by blood to our cells. We have also shown how the combustion of oxygen provides energy, for example, for muscle contraction or to generate electricity in our nerve cells," says Peter Brzezinski, Professor at the Department of Biochemistry and Biophysics, Stockholm University.

The combustion of oxygen in our cells takes place in the so-called respiratory chain that carefully controls the process. Electrons, which come from digestion, are transferred to the oxygen we breathe. The oxygen molecules bind to an enzyme in our mitochondria, the cellular power plant. However, the bound oxygen is not immediately combusted to form water, like in an uncontrolled fire, but it is converted to water gradually in a carefully controlled process. Up until now we only had a very basic knowledge about the mechanism of this process, since the reaction is too rapid too be studied using available techniques. One possibility would be to follow the reactions at low temperatures, at about -50 degrees Celsius, where they would be sufficiently slow. However, this is not practically possible.

In this project, researchers Federica Poiana and Christoph von Ballmoos studied oxygen combustion in a bacterium that lives in hot springs -- they thrive in almost boiling water. When the research group performed their studies at 10 degrees, the bacterium found it extremely cold -- as if our mitochondria were exposed to minus 40 degrees. The reactions then became sufficiently slow to allow studies using available instruments. By combining their experimental studies with theoretical calculations, the researchers could translate their observations to the equivalent processes in human cells.

"In addition to just being curious and wanting learn how the process works, our studies are also motivated by trying to understand the so-called Mitochondrial diseases, caused by malfunction in oxygen combustion," says Peter Brzezinski.

See:

Federica Poiana et al. Splitting of the O–O bond at the heme-copper catalytic site of respiratory oxidases. Science Advances, June 2017 DOI: 10.1126/sciadv.1700279

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.

Tuesday, 18 July 2017

Genetic Data for 1000 Microbes Released


Microbial organisms are a major component of our environment, but scientists have only begun to study their genetic composition in depth. Using current genetic technologies, researchers with the U.S. Department of Energy Joint Genome Institute (DOE JGI) have begun to learn more, and have released their findings. The team has reported 1,003 phylogenetically reference genomes of bacterial and archaeal organisms in Nature Biotechnology.

Genome sequencing and analysis data for 1,003 genomes is now available through the Integrated Microbial Genomes with Microbiomes (IMG/M) system. The DOE JGI is aiming to provide interested scientists with a trove of new sequence data. It could aid in the characterization of biotechnologically relevant secondary metabolites or reveal more about enzymes that act under certain conditions.

According to the Nature paper:

"We present 1,003 reference genomes that were sequenced as part of the Genomic Encyclopedia of Bacteria and Archaea (GEBA) initiative, selected to maximize sequence coverage of phylogenetic space. These genomes double the number of existing type strains and expand their overall phylogenetic diversity by 25%. Comparative analyses with previously available finished and draft genomes reveal a 10.5% increase in novel protein families as a function of phylogenetic diversity. The GEBA genomes recruit 25 million previously unassigned metagenomic proteins from 4,650 samples, improving their phylogenetic and functional interpretation. We identify numerous biosynthetic clusters and experimentally validate a divergent phenazine cluster with potential new chemical structure and antimicrobial activity. This Resource is the largest single release of reference genomes to date. Bacterial and archaeal isolate sequence space is still far from saturated, and future endeavors in this direction will continue to be a valuable resource for scientific discovery."

Posted by Dr. Tim Sandle

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

Saturday, 15 July 2017

Swirling swarms of bacteria offer insights on turbulence


When bacteria swim at just the right speed, swirling vortices emerge. As those patterns disintegrate into chaos, physicists detect a telling mathematical signature.

In physical systems, turbulence emerges when the smooth flow of a liquid or gas is disrupted, producing unpredictable swirls like those in billowing smoke, foaming surf, and a stomach-dropping flight. Try as they might, scientists still cannot predict precisely how smoke, water, air, or any other substance will move about during turbulence.

Something similar appears to happen within certain biological systems. Recently, scientists have discovered a turbulence-like dynamic emerging from what they call active fluids, such as a dense mass of swimming bacteria or a collection of movement-generating proteins suspended in liquid. Unlike a drop of water, these active fluids move on their own power. The biological turbulence they generate therefore differs in some significant ways from the physical phenomenon, and the relationship between these two types of turbulence remains controversial and poorly understood.

The discovery bridges the two by showing that as it emerges and propagates, turbulence follows the same pattern in masses of swimming bacteria as it does in air, water, or any other physical system.

See:

Amin Doostmohammadi, Tyler N. Shendruk, Kristian Thijssen, Julia M. Yeomans. Onset of meso-scale turbulence in active nematics. Nature Communications, 2017; 8: 15326 DOI: 10.1038/NCOMMS15326

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.

See:

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

Thursday, 13 July 2017

First human antibodies to work against all Ebola viruses


After analyzing the blood of a survivor of the 2013-16 Ebola outbreaks, a team of scientists from academia, industry and the government has discovered the first natural human antibodies that can neutralize and protect animals against all three major disease-causing Ebola viruses. The findings could lead to the first broadly effective Ebola virus therapies and vaccines.

Ebola viruses infections are usually severe, and often fatal. There are no vaccines or treatments approved by the Food and Drug Administration for treating these viruses. Some two dozen Ebola virus outbreaks have occurred since 1976, when the first outbreak was documented in villages along the Ebola River in the Democratic Republic of Congo (formerly Zaire). The largest outbreak in history -- the 2013-16 Western African epidemic -- caused more than 11,000 deaths and infected more than 29,000 people.

Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as one of the most promising treatments for Ebola patients. A critical problem, however, is that most antibody therapies target just one specific Ebola virus. For example, the most advanced therapy -- ZMappTM, a cocktail of three monoclonal antibodies -- is specific for Ebola virus (formerly known as "Ebola Zaire"), but doesn't work against two related Ebola viruses (Sudan virus and Bundibugyo virus) that have also caused major outbreaks.

Studies showed that the two antibodies isolated from the Ebola patient work by interfering with a critical step in the process by which ebolaviruses infect cells and then multiply inside them. The two antibodies encounter the virus while it's still in the bloodstream, and bind to glycoproteins (proteins to which carbohydrate chains are attached) that project from its surface. The virus, with its hitchhiking antibodies still bound to it, then attaches to a cell and enters the lysosome -- a membrane-bound structure within the cell that is filled with enzymes for digesting foreign and cellular components. The virus must then fuse with the lysosome membrane to escape into the host cell's cytoplasm, where it can multiply. However, the antibodies prevent the virus from breaking out of its lysosomal "prison," thus stopping infection in its tracks.

See:

Anna Z. Wec, Andrew S. Herbert, Charles D. Murin, Elisabeth K. Nyakatura, Dafna M. Abelson, J. Maximilian Fels, Shihua He, Rebekah M. James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R. Bakken, Eileen Goodwin, Hannah L. Turner, Rohit K. Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R. Lai, Laura M. Walker, Andrew B. Ward, John M. Dye, Kartik Chandran, Zachary A. Bornholdt. Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses. Cell, 2017; 169 (5): 878 DOI: 10.1016/j.cell.2017.04.037

Posted by Dr. Tim Sandle

Wednesday, 12 July 2017

Modified experimental vaccine protects monkeys from malaria


Researchers have modified an experimental malaria vaccine and showed that it completely protected four of eight monkeys that received it against challenge with the virulent Plasmodium falciparum malaria parasite. In three of the remaining four monkeys, the vaccine delayed when parasites first appeared in the blood by more than 25 days.

Malaria symptoms occur when parasites replicate inside red blood cells and cause them to burst. To enter blood cells, the parasite first secretes its own receptor protein, RON2, onto the cell's surface. Another parasite surface protein, AMA1, then binds to a specific portion of RON2, called RON2L, and the resulting complex initiates attachment to the outer membrane of the red blood cell.

Several experimental malaria vaccines previously tested in people were designed to elicit antibodies against AMA1 and thus prevent parasites from entering blood cells. Although AMA1 vaccines did generate high levels of antibodies in humans, they have shown limited efficacy in field trials in malaria-endemic settings.

To improve vaccine efficacy, the NIAID scientists modified an AMA1 vaccine to include RON2L so that it more closely mimics the protein complex used by the parasite. Monkeys were vaccinated with either AMA1 alone or with the AMA1-RON2L complex vaccine. Although the overall levels of antibodies generated did not differ between the two groups, animals vaccinated with the complex vaccine produced much more neutralizing antibody, indicating a better quality antibody response with AMA1-RON2L vaccination. Moreover, antibodies taken from AMA1-RON2L-vaccinated monkeys neutralized parasite strains that differed from those used to create the vaccine. This suggests, the authors note, that an AMA1-RON2L complex vaccine could protect against multiple parasite strains. Taken together, the data from this animal study justify progression of this next-generation AMA1 vaccine toward possible human trials, they conclude.

See:

Prakash Srinivasan, G. Christian Baldeviano, Kazutoyo Miura, Ababacar Diouf, Julio A. Ventocilla, Karina P. Leiva, Luis Lugo-Roman, Carmen Lucas, Sachy Orr-Gonzalez, Daming Zhu, Eileen Villasante, Lorraine Soisson, David L. Narum, Susan K. Pierce, Carole A. Long, Carter Diggs, Patrick E. Duffy, Andres G. Lescano, Louis H. Miller. A malaria vaccine protects Aotus monkeys against virulent Plasmodium falciparum infection. npj Vaccines, 2017; 2 (1) DOI: 10.1038/s41541-017-0015-7

Posted by Dr. Tim Sandle

Tuesday, 11 July 2017

Bioelectricity - a new weapon to fight infection


Changing natural electrical signaling in non-neural cells improves innate immune response to bacterial infections and injury. Tadpoles that received therapeutics, including those used in humans for other purposes, which depolarized their cells had higher survival rates when infected with E. coli than controls. The research has applications for treatment of emerging diseases and traumatic injury in humans.

Transmembrane potential (Vmem) -- voltage potential caused by differences in negative and positive ions on opposite sides of a cell's membrane -- is known to play a critical role in many essential functions in numerous cell types, and the researchers hypothesized that it also could affect innate immunity. In the study, embryonic Xenopus laevis frogs infected with human pathogenic E. coli bacteria were exposed to compounds, including some used in human medicine, to either depolarize (positively charge) or hyperpolarize (negatively charge) their cells. Developing X. laevis frogs are a popular model for regenerative, developmental, cancer and neurobiological studies.

See:

Jean-François Paré, Christopher J. Martyniuk, Michael Levin. Bioelectric regulation of innate immune system function in regenerating and intact Xenopus laevis. npj Regenerative Medicine, 2017; 2 (1) DOI: 10.1038/s41536-017-0019-y

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

Sunday, 9 July 2017

Smartphone microscope creates interactive tool for microbiology


A new 3-D printed, easily assembled smartphone microscope developed at Stanford University turns microbiology into game time. The device allows kids to play games or make more serious observations with miniature light-seeking microbes called Euglena.

"Many subject areas like engineering or programming have neat toys that get kids into it, but microbiology does not have that to the same degree," said Ingmar Riedel-Kruse, an assistant professor of bioengineering. "The initial idea for this project was to play games with living cells on your phone. And then it developed much beyond that to enable self-driven inquiry, measurement and building your own instrument."

Riedel-Kruse named his device the LudusScope after the Latin word "Ludus," which means "play," "game" or "elementary school."

The LudusScope consists of a platform for the microscope slide where the Euglena swim freely, surrounded by four LEDs. Kids can influence the swimming direction of these light-responsive microbes with a joystick that activates the LEDs.

Above the platform, a smartphone holder positions the phone's camera over a microscope eyepiece, providing a view of the cells below.

On the phone, children can run a variety of software that overlay on top of the image of the cells. One looks like the 1980s video game Pac-Man, with a maze containing small white dots. Kids can select one cell to track, then use the LED lights to control which direction the cell swims in an attempt to guide it around the maze and collect the dots. Another game looks like a soccer stadium. Kids earn points by guiding the Euglena through the goal posts.

See:

Honesty Kim, Lukas Cyrill Gerber, Daniel Chiu, Seung Ah Lee, Nate J. Cira, Sherwin Yuyang Xia, Ingmar H. Riedel-Kruse. LudusScope: Accessible Interactive Smartphone Microscopy for Life-Science Education. PLOS ONE, 2016; 11 (10): e0162602 DOI: 10.1371/journal.pone.0162602

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."

See:

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