Tuesday, 18 June 2019

New research shows weakness with antimicrobial paints

Antimicrobial paints offer the promise of extra protection against bacteria. But Northwestern University researchers caution that these paints might be doing more harm than good.
In a new study, the researchers tested bacteria commonly found inside homes on samples of drywall coated with antimicrobial, synthetic latex paints. Within 24 hours, all bacteria died except for Bacillus timonensis, a spore-forming bacterium. Most bacilli are commonly inhabit soil, but many are found in indoor environments.

"If you attack bacteria with antimicrobial chemicals, then they will mount a defense," said Northwestern's Erica Hartmann, who led the study. "Bacillus is typically innocuous, but by attacking it, you might prompt it to develop more antibiotic resistance."

Bacteria thrive in warm, moist environments, so most die on indoor surfaces, which are dry and cold, anyway. This makes Hartmann question the need to use antimicrobial paints, which may only be causing bacteria to become stronger.

Spore-forming bacteria, such as Bacillus, protect themselves by falling dormant for a period of time. While dormant, they are highly resistant to even the harshest conditions. After those conditions improve, they reactivate.

"When it's in spore form, you can hit it with everything you've got, and it's still going to survive," said Hartmann, assistant professor of civil and environmental engineering in Northwestern's McCormick School of Engineering. "We should be judicious in our use of antimicrobial products to make sure that we're not exposing the more harmless bacteria to something that could make them harmful."

One problem with antimicrobial products -- such as these paints -- is that they are not tested against more common bacteria. Manufacturers test how well more pathogenic bacteria, such as E. coli or Staphylococcus, survive but largely ignore the bacteria that people (and the products they use) would more plausibly encounter.

"E. coli is like the 'lab rat' of the microbial world," Hartmann said. "It is way less abundant in the environment than people think. We wanted to see how the authentic indoor bacteria would respond to antimicrobial surfaces because they don't behave the same way as E. coli."


Jinglin Hu, Sarah B. Maamar, Adam J. Glawe, Neil Gottel, Jack A. Gilbert, Erica M. Hartmann. Impacts of Indoor Surface Finishes on Bacterial Viability. Indoor Air, 2019; DOI: 10.1111/ina.12558

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 17 June 2019

Cleanroom Particle Counting: Assessing Data for Trends and Patterns

Given the requirement for particle count trending it is surprising that there is little published on the subject and a paucity of examples for the reader to assess. While there are many different approaches that can be taken, improvements to quality reporting are driven through example. To partly address the shortfall of literature on particle count trending, this paper considers some different ways to assess particle data, in terms of routine assessments and where a statistical comparison of data is required. With the latter, this is less straightforward given that particle count data does not follow normal distribution.

In relation to this, Tim Sandle has written a new paper. The reference is:

Sandle, T. (2019) Cleanroom Particle Counting: Assessing Data for Trends and Patterns, Journal of GxP Compliance, 23 92): 1-10

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 16 June 2019

Why certain strains of bacteria are associated with diabetic wounds that do not heal

About 10 percent of U.S. citizens have been diagnosed with diabetes, and one quarter of these patients will develop a wound that does not heal. In the worst case outcome, which occurs in up to 25 percent of these wound-developing patients, the wounds will require an amputation. Many patients who develop these ulcers may not notice the initial signs, since the high blood glucose of diabetes can lead to a lack of feeling and deformation of the feet. As a result, patients with diabetes commonly develop foot ulcers that may go unnoticed over time.

Current treatments are insufficient, meaning patients can live with these wounds for months or even years without healing. The mortality rate associated with diabetic foot ulcers is equivalent to that of breast cancer and prostate cancer combined -- higher than 70 percent when they lead to amputation.

"While wounds don't receive the attention of other diseases, they're incredibly common, and our study increases our understanding of how microbes impair or promote healing," said the study's senior author Elizabeth Grice, PhD, an associate professor of Dermatology. The lead author, Lindsay Kalan, PhD, now an assistant professor of Medical Microbiology and Immunology at the University of Wisconsin School of Medicine and Public Health, began this work as a post-doctoral researcher in Grice's lab.

Previous studies have used lower resolution techniques to catalogue the microbes that reside in chronic wounds. This study built on that research by using higher resolution DNA sequencing to identify specific species and subspecies and how they are related to patient outcomes. Researchers collected samples from 46 patient ulcers every two weeks for six months, or until the wound healed or was amputated.

S. aureus, a common and difficult-to-treat pathogen, was found in the majority of wounds, but researchers note the presence of the bacteria itself did not predict whether or not a wound would heal. However, the high resolution DNA sequencing showed certain strains of S. aureus were only in the wounds that did not heal over the course of the study. Further testing revealed that the "non-healing" strain was better equipped to cause tissue damage and evade antibiotic treatments. Researchers further validated their findings in mice.

They also noted that another common microbe found in diabetic wounds, Alcaligenes faecalis, was associated with quicker healing.

"It is possible there are bacteria that actually benefit the wound, and we can use what we learned in this study to develop new treatment strategies for non-healing wounds," Grice said. "We hope this research will eventually help identify patients at risk for bad outcomes and lead to treatment innovations that these patients desperately need."

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 15 June 2019

On-chip drug screening for identifying antibiotic interactions in eight hours

A KAIST research team developed a microfluidic-based drug screening chip that identifies synergistic interactions between two antibiotics in eight hours. This chip can be a cell-based drug screening platform for exploring critical pharmacological patterns of antibiotic interactions, along with potential applications in screening other cell-type agents and guidance for clinical therapies.

Antibiotic susceptibility testing, which determines types and doses of antibiotics that can effectively inhibit bacterial growth, has become more critical in recent years with the emergence of antibiotic-resistant pathogenic bacteria strains.

To overcome the antibiotic-resistant bacteria, combinatory therapy using two or more kinds of antibiotics has been gaining considerable attention. However, the major problem is that this therapy is not always effective; occasionally, unfavorable antibiotic pairs may worsen results, leading to suppressed antimicrobial effects. Therefore, combinatory testing is a crucial preliminary process to find suitable antibiotic pairs and their concentration range against unknown pathogens, but the conventional testing methods are inconvenient for concentration dilution and sample preparation, and they take more than 24 hours to produce the results.

To reduce time and enhance the efficiency of combinatory testing, Professor Jessie Sungyun Jeon from the Department of Mechanical Engineering, in collaboration with Professor Hyun Jung Chung from the Department of Biological Sciences, developed a high-throughput drug screening chip that generates 121 pairwise concentrations between two antibiotics.
The team utilized a microfluidic chip with a sample volume of a few tens of microliters. This chip enabled 121 pairwise concentrations of two antibiotics to be automatically formed in only 35 minutes.

They loaded a mixture of bacterial samples and agarose into the microchannel and injected reagents with or without antibiotics into the surrounding microchannel. The diffusion of antibiotic molecules from the channel with antibiotics to the one without antibiotics resulted in the formation of two orthogonal concentration gradients of the two antibiotics on the bacteria-trapping agarose gel.

The team observed the inhibition of bacterial growth by the antibiotic orthogonal gradients over six hours with a microscope, and confirmed different patterns of antibiotic pairs, classifying the interaction types into either synergy or antagonism.
Professor Jeon said, "The feasibility of microfluidic-based drug screening chips is promising, and we expect our microfluidic chip to be commercialized and utilized in near future."

See: Seunggyu Kim, Fahim Masum, Ju-Kang Kim, Hyun Jung Chung, Jessie S. Jeon. On-chip phenotypic investigation of combinatory antibiotic effects by generating orthogonal concentration gradients. Lab on a Chip, 2019; 19 (6): 959 DOI: 10.1039/c8lc01406j

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 14 June 2019

How E. coli clones take over human gut

Researchers from University of Birmingham investigated how and why a clone of E. coli called ST131 -- dubbed a 'superbug' because it is resistant to multiple drugs -- has become the major cause of drug resistant E. coli infections, but not so dominant that it has wiped out other clones that do not have multi-drug resistance.

Escherichia coli (E. coli) is a type of bacteria common in human and animal intestines, and forms part of the normal gut flora -- the bacteria that exist in the bowel. There are a number of different types of E. coli and, while the majority are harmless, some can cause serious food poisoning or infections including in the urinary tract or bloodstream.

The number of cases of E. coli have risen by 27% from 32,309 in 2012-13 to 41,060 in 2017-18. The rise has been linked to an increase in antibiotic resistant infections caused by so-called 'superbugs'.

The most globally dominant clone of E. coli that is resistant to multiple drugs is called ST131. Earlier research has shown that while ST131 emerged and rapidly spread in the late 1990s, it caused no more than 20% of clinical cases of E. coli once it had emerged on the scene. This is because of a type of evolutionary selection called negative frequency dependency selection (NFDS).

It is now known that while there are significantly dominant drug resistant clones of E. coli such as ST131 and other new ones are emerging all the time, it seems highly unlikely that any of them are ever going to become a completely dominant clone because this process called NFDS controls the balance across the whole E. coli population.

As part of the research the scientists also analysed almost 1,000 genome sequences of strains within ST131 to see if they could find any genetic patterns that may explain how this process happens. It was found that in the ST131 clone there was a lot of variation in the genes that are involved in allowing the bacteria to colonize in the human gut when compared to those in non-drug resistant bacteria that are very closely related to ST131.

The implications are that if a person is going to get a bloodstream or urinary infection from E. coli it usually comes after it has colonized in the gut, therefore we now know that genetically something has happened to this superbug which allows it to colonise the gut far more competitively than other E. coli.

See: Alan McNally, Teemu Kallonen, Christopher Connor, Khalil Abudahab, David M. Aanensen, Carolyne Horner, Sharon J. Peacock, Julian Parkhill, Nicholas J. Croucher, Jukka Corander. Diversification of Colonization Factors in a Multidrug-Resistant Escherichia coli Lineage Evolving under Negative Frequency-Dependent Selection. mBio, 2019; 10 (2) DOI: 10.1128/mBio.00644-19

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 13 June 2019

The mystery of antimicrobial frog secretions

The Bombina variegata frog, also known as Yellow Bellied Toad, inhabits the forests, grasslands, wetland, and aquatic habitats across Central Europe. Their skin secretions contain antimicrobial agents -- called Bominin H2 and H4 -- that play a key role in protecting the species against infection.

Bombinin H2 and H4 are antimicrobial peptides (AMPs) -- or host defense peptides -- that play an important function in immune response. They have attracted attention for their ability to inhibit Leishmaniasis -- a highly infectious and potentially fatal tropical disease that has affected an estimated 20 million people worldwide, with 1.3 million new cases and 20,000 to 30,000 deaths reported each year.

H4 is an isomer of H2 -- they share the same formula but the atoms in the molecule are arranged differently -- with H4 having a naturally occuring D-amino acid at the end of the molecular chain. In terms of its antimicrobial properties, H4 is more potent than H2, but until now, the reason has remained an unsolved biological mystery.

In order to gain a better understanding of the molecular mechanism that drives the antimicrobial activity of Bombinin H2 and H4 peptides and what makes H4 more effective than H2 in this regard, the authors conducted electrophysiological experiments on a lipid bilayer membrane that replicated the lipid membrane surrounding cells or microorganisms The results were then analyzed using existing AMP models to determine how efficient these antimicrobial peptides are at disrupting the cell membrane of microbes.

The team found that H2 and H4 peptides inhibit microbial activity by making holes in the cell membrane of microorganisms, causing ions to leak out of the cell, which ultimately kills them. The efficiency of this anti-microbial activity is affected by ion permeability (how fast ions leak out of the cell), the speed of pore formation, and the size of the pores formed.
The results indicate that the peptides' ability to transform into another molecule with the same atomic composition but with atoms arranged differently facilitates faster pore formation. While H2 forms larger pores than H4, H4 forms pores more rapidly. A mixture of H2/H4, meanwhile, forms medium-sized pores at a slower rate than H4, but the presence of the D-amino acid enhances the binding affinity to the lipid membrane, thereby improving its disruptive abilities.

In terms of what this means, think of it like a field of different sized pit traps; larger traps take longer to dig, but can trap more animals than a smaller pit. On the other hand, one can dig many smaller pits in the same time it takes to dig just a few large ones. Digging medium sized pit traps and adding bait or a lure that would attract animals to the pit, would be the most effective approach of all.

Unravelling the molecular mechanism that facilitates antimicrobial activity of these peptides can help us better understand how the defense system of the frog has evolved, and how this can be used to fight microbial infections of medical importance.

The ultimate goal is to use this mechanism to develop better antimicrobial agents, especially antimicrobial agents that are effective against antibiotic-resistant bacteria.


Yusuke Sekiya, Keisuke Shimizu, Yuki Kitahashi, Akifumi Ohyama, Izuru Kawamura, Ryuji Kawano. Electrophysiological Analysis of Membrane Disruption by Bombinin and Its Isomer Using the Lipid Bilayer System. ACS Applied Bio Materials, 2019; 2 (4): 1542 DOI: 10.1021/acsabm.8b00835

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 12 June 2019

Skin microbiome summit showcases scientific developments for treating skin conditions

The Nestlé Skin Health SHIELD Skin Microbiome Summit in New York showcased the rapid research developments which have been advancing in recent years. Professor Cath O’Neil of Manchester University, a pioneer in the skin biome, who is also CEO of SkinBioTherapeutics, welcomed the scientific focus on treating the many conditions that make life miserable for patients with skin conditions.

Professor O’Neil commented “Unfortunately there are many skin products which make claims which are not scientifically proven. It is excellent when major companies sponsor these scientific forums so that we can really develop products which work.”

The skin microbiome, or the skin microbiota, is the population of bacteria that live on the skin. Over 1,000 species of bacteria have been identified, as well as viruses, funghi, and even mites. Research into the skin microbiome is about 20 years behind research on the gut microbiome, but there is evidence that certain bacteria can help stop pathogenic bacteria growing and causing infections on the skin.

While there have been significant advances in the scientific understanding of the microbiota living on and in our skin, the most exciting research now being conducted focuses on how altering the composition of the skin microbiome could lead to improvements in skin health and even treatments for serious diseases.

SkinBioTherapeutics is at the forefront of this exciting research with its work using ‘lysates’, or extracts, of particular probiotic bacteria to deliver targeted health benefits. The lysates which have been shown to increase the skins barrier integrity; protect the skin from infection by outcompeting harmful pathogens; and increase the rate of skin healing in response to injury.

The target treatment areas for SkinBioTherapeutics are cosmetics, reducing the incidence of eczema flares, and infection prevention. Recently released human study data shows that SkinBioTherapeutics’ therapy is safe and well tolerated, and that it showed a statistically significant increase in skin hydration.

Watch a video of the Nestlé Skin Health SHIELD Skin Microbiome Summit here.

About SkinBioTherapeutics plc

SkinBioTherapeutics is a life science company focused on skin health. The Company’s proprietary platform technology, SkinBiotix®, is based upon discoveries made by Dr. Catherine O’Neill and Professor Andrew McBain.

SkinBioTherapeutics’ platform applies research discoveries made on the activities of lysates derived from probiotic bacteria when applied to the skin. The Company has shown that the SkinBiotix® platform can improve the barrier effect of skin models, protect skin models from infection and repair skin models. Proof of principle studies have shown that the SkinBiotix® platform has beneficial attributes applicable to each of these areas.

SkinBioTherapeutics received seed funding from the Tech Transfer office of the University of Manchester for the discovery of SkinBiotix®. The platform was subsequently spun out of the University of Manchester in March 2016 and was funded by OptiBiotix (AIM: OPTI).

The Company joined AIM in April 2017, concurrent with raising £4.5 million from a placing of new ordinary shares.

The Company is based in Manchester, UK. For more information, visit www.skinbiotherapeutics.com.
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 11 June 2019

Machine learning is transforming the pharma sector

In the U.S., drug companies spend more than $50 billion on R&D, while in Europe spending surpasses €30 billion. To help lower costs and to reduce the time taken for new drugs to hit the market, pharma is turning to machine learning.

The pharmaceutical regulatory environment is becoming more challenging, and drugs must go through extensive testing before they hit the market. As a result, there are major incentives for drug companies to reduce R&D spending in order to free up funds for additional ventures and offer lower prices for their products.

By adopting sophisticated data science, and machine learning, pharmaceutical researchers can save money and time on R&D. On top of that, machine learning technology provides new ways for drug companies to streamline nearly every other aspect of their businesses.

To outline how machine learning can be best applied, data science software company, Dataiku, has recently released a whitepaper titled “How Machine Learning is Transforming Pharmaceuticals”.

The paper assesses how drugs have been discovered in the past and notes that rather than through ‘inspiration’ or years of iterative experimental approach, the next major medical breakthroughs will come as the result of data review and data analysis.

The paper goes on to assess how big data and machine learning are transforming the pharmaceutical industry. The focus is with how big data analytics can improve the patient recruitment process. This involves accessing and searching cloud services, where relevant databases contain terabytes of publicly- and privately-held data to enable clinical trial recruitment with better precision.

Another example is with Natural Language Processing, which speeds up hypothesis testing. When scientists design a drug trial tend to use their own knowledge of medical literature and previous studies. Now algorithms can screen decades of different studies and trials.

A third application is with data science methods, which can assist scientists with identifying patterns in public and private datasets far faster and more meaningfully. Such analytics can also assist with developing personalized medicines, where drugs can be customized to small populations of patients with particular genetic profiles.

Analytics can also aid companies with optimizing the shipping of medications, finding the quickest and most cost-effective routes. A different application is with assessing prescribing rates, to verify that patients genuinely need the medication and to ensure that medics are consistently prescribing drugs based on patient need.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 10 June 2019

Cleanroom Particle Counting: Assessing Data for Trends and Patterns

Airborne particulate content relating to pharmaceuticals and healthcare can be classified as viable or non-viable contaminants and may originate from humans (such as skin matter) or from areas of production (such as opening packaging materials and operating centrifuges or vortexes). The assessment of particles provides the basis of cleanroom classification; however, particle counting is not only an exercise undertaken to assess cleanrooms as part of classification exercises, since particle counting of GMP areas needs to be undertaken on a regular basis in order to show on-going compliance (notwithstanding that a cleanroom that meets the particle concentration requirements, but does not result in the desired level of bioburden, will clearly be inadequate). Ongoing compliance is best assessed by looking at data patterns over time and by comparing cleanrooms in different states, for different activities, and at different time points. Indeed, both ISO 14644-2: 2015 and EU GMP Annex 1 recommend regular assessments and the examination of data patterns by trending.

Given the requirement for particle count trending it is surprising that there is little published on the subject and a paucity of examples for the reader to assess. While there are many different approaches that can be taken, improvements to quality reporting are driven through example. To partly address the shortfall of literature on particle count trending, this paper considers some different ways to assess particle data, in terms of routine assessments and where a statistical comparison of data is required. With the latter, this is less straightforward given that particle count data does not follow normal distribution.

In relation to this, Tim Sandle has written a new paper. The reference is:

Sandle, T. (2019) Cleanroom Particle Counting: Assessing Data for Trends and Patterns, Journal of GxP Compliance, 23 92): 1-10

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 9 June 2019

Microbiome Science Roundup

Effects of a diet based on inulin-rich vegetables on gut health and nutritional behavior in healthy humans: A group led by Nathalie Delzenne took on the difficult task of studying a prebiotic dietary intervention in healthy individuals. Their approach was to measure not only gastrointestinal symptoms, but also food-related thoughts / behaviors. They discovered when healthy people consumed vegetables rich in inulin-type fructans, they reported higher satiety and less desire to eat foods that were sweet or salty—and somewhat surprisingly, these feelings persisted for several weeks after the intervention was complete. The intervention also reduced gut microbiota richness and induced changes in particular microbial taxa.

News from Microbiome Times

Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease: When someone with Crohn’s disease undergoes ileal resection, predicting the recurrence of disease is currently difficult. This group looked at the gut microbiota of patients at the time of surgery, and found certain bacterial taxa that appeared to predict disease relapse.

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders: These researchers found that the composition of the small intestinal microbiota – while difficult to sample – correlates better with IBS symptoms than does a duodenal aspirate culture. And sure enough, a dietary intervention that triggered gut IBS symptoms also had pronounced effects on small intestinal microbes.

Metabolomics reveals elevated urinary excretion of collagen degradation and epithelial cell turnover products in irritable bowel syndrome patients: This small study found a panel of ten metabolites in the urine that seemed to distinguish people with IBS from people without IBS. (A limitation of this study was that the participants had many different co-morbid conditions.)

Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome: This month’s IBS papers were topped off by a sophisticated multi-omics analysis in IBS from collaborators at Baylor College of Medicine (USA). In a population of children aged 7 to 12, these researchers found gut bacterial taxa, genes / pathways, and metabolites that could combine to identify those with IBS. They even found specific ones that were associated with abdominal pain, the main troubling symptom in children with IBS.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 8 June 2019

Live Lactobacilli as a Solution to Improve Skin Health

Topical application of beneficial lactobacilli and potentially other ‘live biotherapeutic products’ (LBPs) show great potential as an alternative strategy to tackle skin care problems related to disturbance of the skin microbiome, providing alternatives to the overuse of antibiotics in skin care.

Microbiome Times caught up with Dr Ingmar Claes, CSO of YUN, a Belgian biotech company spun-out from the University of Antwerp to learn more about how they are developing LBPs to treat skin conditions.

Here is an extract:

While there has been much debate on what constitutes a healthy microbiome, it is clear that it is all a matter of balance. Differences in the skin microbiome composition, either in diversity (alpha and beta diversity between body sites) and in the specific taxonomics strains present exist between individuals and skin locations. However, we now know which typical genera are present on the human skin based on the body site and whether it is dry, moist or sebaceous. Taking acne vulgaris as an example, it is specific Cutibacterium spp. (formerly known as Propionibacterium acnes) and also Staphylococci that play an important role in the pathophysiology of acne, the induction of inflammation and the formation of papules and pustules, i.e. ‘pimples’

To read the article, go to: http://www.microbiometimes.com/biotech-focus-live-lactobacilli-as-a-solution-to-improve-skin-health/
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 7 June 2019

The bacteria building your baby

Exposure to influential bacteria begins before we are born, new evidence confirms

Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

They carefully collected amniotic fluid samples from 50 healthy women undergoing planned caesarean deliveries, and found that nearly all (36/43 viable samples) contained bacterial DNA. What’s more, all 50 newborns had bacteria in their first poop.

Published in Frontiers in Microbiology, the study used uniquely rigorous contamination controls to confirm that exposure to bacteria begins in the womb – and could help to shape the developing fetal immune system, gut and brain.

The not-so-sterile womb

“Over the last decade, numerous studies have detected bacterial DNA in amniotic fluid and first-pass meconium [baby’s first poop], challenging the long-held assumption that the womb is sterile,” explains lead author Lisa Stinson, of the University of Western Australia. “However, some argue that the results are false positives – contaminants in the reagents used in DNA analysis.”

It is important to conclusively determine whether the healthy womb harbors bacteria, say the researchers, because this ‘fetal microbiome’ would likely have a significant impact on the developing immune system, gut, and brain.

The fetal microbiome
To settle the issue, Stinson and colleagues took strict measures to eliminate bacterial contamination when analyzing amniotic fluid and meconium samples. For example, they purified the reagents used to amplify traces of bacterial DNA in the samples, by adding an enzyme which digests DNA remnants from biomanufacturing.

“Despite these measures, we still found bacterial DNA in almost all samples,” reports Stinson.

“Interestingly, the meconium microbiome varied hugely between individual newborns. The amniotic fluid microbiome for the most part contained typical skin bacteria, such as Propionibacterium acnes and Staphylococcus species.”

A developmental role

But what might these bacteria be doing in the womb?

None of these women or their babies had any sign of infection. In fact, the fetal microbiome may prove to be a beneficial regulator of early development.

“We found that levels of important immune modulators in meconium and inflammatory mediators in amniotic fluid varied according to the amount and species of bacterial DNA present. This suggests that the fetal microbiome has the potential to influence the developing fetal immune system.”

There is one small caveat – technically, the DNA in these samples could have come from bacteria that were already dead in the womb.

“Here we’ve proven that bacterial DNA is present in the womb, but the next step will be to show whether these are alive and constitute a true microbiome,” concludes Stinson.

To read more, see: https://www.frontiersin.org/articles/10.3389/fmicb.2019.01124/full

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 6 June 2019

Creating ‘smart’ microbial bionsensors

New research shows that protein-based biosensors can detect the presence of a desired enzyme target and respond by physically lighting up, and enabling researchers to immediately identify cells with increased overall enzyme yield.

The implications of this smart microbial cell concept are to offer an advanced platform for high throughput screening for enzyme discovery, design, and evolution. The approach, which comes from Los Alamos National Laboratory, can be translated to screening of metagenomic samples, rational enzyme design, or directed evolution of known enzymes. The technology is adaptable to a single enzyme, or a pathway, or global optimization of an industrial strain.

To discover more, I spoke with researcher Ramesh Jha.

Tim Sandle: How important are biofuels in terms of addressing energy demand?

Ramesh Jha: Biofuels and commodity chemicals made from renewable biomass using enzymes or microbes are considered sustainable routes and their use circumvents dependency on fossil fuels. Added to that, fuels and commodity chemicals come with a high carbon footprint while biofuels and biocommodities from renewable sources is an efficient recycling of carbon and leave a low carbon footprint.

Tim Sandle: What are the different types of biofuels and how do they differ in terms of production?

Jha: Various biofuels, biocommodities and bioplastics can be ‘drop in’ or ‘functional replacements’ of the existing fuels, commodity chemicals or polymers mostly derived from petroleum sources.

Tim Sandle: How did you develop your protein-based biosensors?

Jha: Our protein-based biosensors are inspired by nature, where a class of proteins called transcription factors (TF) gets activated in the presence of a molecule and regulate the production of other proteins for function (OPF) . If TF is engineered to interact with an enzymatic product and the OPF is a fluorescent protein reporter, then the enzymatic activity in a microbial cell can be correlated to the fluorescence response in the cell.

Tim Sandle: How do the biosensors identify the desired enzyme target?

Jha: Enzymatic activity results in a chemical product. This product activates the biosensor, which responds by producing and accumulating a fluorescence "reporter." The enzymatic activity is visualized by the presence of light.

Tim Sandle: What are the practical benefits of this identification?

Jha: What we see, we believe. Cellular fluorescence due to the enzymatic activity can be easily visualized using a flow cytometer with ultra high throughput and sensitivity. Measuring the product in a cell is otherwise a tedious and slow step.


A biofuel is a fuel that is produced through biological processes (such as agriculture) as opposed to geological processes (like fossil fuels). Renewable biofuels either involve carbon fixation, such as those that occur in plants or microalgae through the process of photosynthesis; or, they are created by the conversion of plant material.

Tim Sandle: Has industry shown an interest in this development, in relation to biofuels?

Jha: Industries are interested in testing millions of variants of microbial strains or enzymes. Since the biosensor technology can be easily adapted for high-throughput screening, industries are getting interested in this technology.

Tim Sandle: Are there any other practical applications for this technology?

Jha: This technology can be applied to optimization of enzymes or microbial strains with applications in biomanufacturing as well as medical therapeutics and environmental clean-up.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 5 June 2019

What is low-density lipoprotein (LDL) heart disease?

Image: Manu5

Cholesterol cannot be transported in blood on its own and is attached to hydrophilic proteins that function as transport vehicles for moving different types of fats such as cholesterol, triglycerides, and phospholipids. It is associated with the basic nature of fats that they are insoluble in water.

These combinations of fats and protein are called lipoproteins.

Mainly, there are five different types of lipoprotein namely chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL).

LDL, the "bad" cholesterol is the type puts your heart at risk.

It gathers in the walls of your blood vessels, where it could result in blockages.

Raised levels of LDL add to your chances of a heart attack and the reason behind that is the sudden blood clot that shapes there.

If the LDL level is high, that means that you have too much LDL cholesterol in your blood. This extra LDL, along with other substances, forms plaque.

The plaque builds up in your arteries and causes the arteries to become hardened and narrowed, which slows down or blocks the blood flow to the heart. As blood carries oxygen to heart, such a condition means that your heart may not be able to get enough oxygen which causes chest pain.

If the blood flow is completely blocked, it causes a heart attack. Higher levels of LDL raise the probability an of heart disease.

It's based on your how likely it is you’ll have heart disease or a stroke.

Factors like your age, cholesterol level, blood pressure whether you smoke or take blood pressure medicine affect your chance of having a heart problem.

While if you have Diabetes or a history of heart disease in your family, also contribute to chances of a stroke.

A particular kind of medication that can lower your cholesterol and regular exercise, that gets your heart pumping, lowers your LDL levels.

Further, if you can add foods low in saturated fat, cholesterol, simple carbs (like sugar, white bread), fiber and plant sterols to your diet, you can lower your numbers even more.

On the other hand, many people have high blood cholesterol throughout their lifetime without ever developing heart disease.

About Author

Krishna writes about digital marketing, healthcare, market research (straitsresearch.com) and has a lot of working experience with international companies. He has extensive experience developing marketing, corporate communications, and public relations materials in a variety of fields including finance, business, chemical, healthcare and technology.

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