Tuesday, 19 February 2019

Alternations in gut microbiota in pregnancy

Recent studies have shown that maternal gut microbiota in humans primes the offspring's immune and metabolic development during pregnancy and lactation. Due to environmental factors that are impractical to control in human studies, however, much remains unknown around changes in maternal gut microbiota during these stages. A new study published in The FASEB Journal utilized a pig model to enable exploration of maternal gut microbiota change due to pregnancy and lactation.

To rule out the confounding factors in human studies of diet and host genetics, a group of researchers examined fresh fecal samples from two breeds of sows. Based on these samples, they conducted comparative analyses of gut microbiota (including Coriobacteriaceae and Escherichia) and short-chain fatty acids (SCFAs) across different stages of gestation, lactation, and non-pregnancy.

Coriobacteriaceae and Escherichia were found to gradually increase over gestational time irrespective of breed, indicating that they are likely associated with the progression of pregnancy. Relative to the gestation and non-pregnancy periods, lactation was associated with an increase in SCFA production in both breeds, suggesting that this phase has a distinct gut microbial structure and higher metabolic activity than the other phases.


Hongbin Liu, Chengli Hou, Ning Li, Xiaoya Zhang, Guolong Zhang, Feiyun Yang, Xiangfang Zeng, Zuohua Liu, Shiyan Qiao. Microbial and metabolic alterations in gut microbiota of sows during pregnancy and lactation. The FASEB Journal, 2019; fj.201801221RR DOI: 10.1096/fj.201801221RR

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 18 February 2019

E-learning module from Pharmig supports Annex 1 disinfection requirements

In December 2017, the European Medicines Agency issued a new draft of EU GMP Annex 1 for sterile medicinal products manufacture. 1 While the draft has yet to be converted into a finalised document, much of what is contained within the document is being used by European inspectors to assess facilities (this is unsurprising given that the revisions are intended to codify current best practices). Central to the update is the requirement for each facility to develop a contamination control strategy, and central to such a strategy is the cleaning and disinfection of cleanrooms. The application of detergents and disinfectants to well-designed and operated cleanrooms is essential for contamination control.

Tim Sandle has written a new article on e-learning solutions for cleaning and disinfection practices:

Pharmig, the not-for-profit professional organisation representing pharmaceutical microbiologists, has recognised these trends and the associated need to address cleaning and disinfection training and competency standards. Part of Pharmig’s remit is to develop training and education in relation to microbiology. Weighing up different options for delivering training, Pharmig selected an e-learning route and subsequently developed an interactive training package. This article considers the benefits of e-learning, the new on-line module from Pharmig, as well as the key requirements from the revised Annex 1 in relation to disinfection contamination control.


Sandle, T. (2018) E-learning module from Pharmig supports Annex 1 disinfection requirements, Clean Air and Containment Review, Issue 36: 20-23

For details contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 17 February 2019

The Problem of Bacterial Spores and Sporicidal Disinfection (webinar)

There have been a number of pharmaceutical and healthcare product recalls associated with bacterial contamination, and a number of these are associated with spore forming organisms. In addition, there have been some reported cases of patient illness, especially in relation to aseptically produced medicines. Investigations have shown that poor contamination control has led to spores being prevalent in the production environment. Improved contamination control strategies are required to prevent such incidents from occurring.

Incidents of bacterial spore contamination of medicinal products are increasing. Regulators are concerned about the link between product recalls and the process environment. Pharmaceutical and healthcare facilities need to have a robust bio-contamination control program in place. This webinar outlines the origins and risks of spores, strategies to reduce incidents, and the selection and incorporation of sporicidal agents into the contamination control program.

Date: Thursday, 21 February 2019 | Time: 10:00 AM PST, 01:00 PM EST | Duration: 60 Minutes

See: https://onlinecompliancepanel.com/webinar/The-Problem-of-Bacterial-Spores-and-Sporicidal-Disinfection-505059

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

How to save time in autoclaving cycles

The normal packaging activity inside a cleanroom solicits some fundamental reflections on the times, effectiveness and safety of the operation itself:

● packaging is a time-consuming operation
● the use of medical paper involves risks related to the nature of the intrinsically weak material, which is corruptible after autoclaving, subject to breakage if wet, and with a medium-quality microbiological barrier
● the safety of the entire operation, as regards the possible release of particles and the uniformity of sterilization, is compromised

Pharmaclean® line of covers and bags for packaging, protection and sterilization solves time, efficacy and safety problems at the same time.

In this case a filling needle: the application is simple and fast, as well as the closure (without adhesive tape). In a short time, we are ready for autoclaving.

After applying the cover to the part of the tube terminal, insert the filling needle into the dedicated bag. We are ready for the sterilization phase.

The use of Pharmaclean® covers and bags makes the packaging operation and subsequent sterilization, fast, effective and safe.

● tear and puncture resistance
● easy to remove
● closure with laces, no adhesive tape
● possibility of customization
● no limit of shape or size
● low particle release
● excellent microbiological barrier
● uniform steam penetration over the entire surface
● ease in preparing the instruments
● protects against microbiological and particulate contamination during the various stages of the production process

Pharmaclean® produces standard and customized covers and bags according to the specific needs of the individual customer.

The use of Tyvek®, compared to medical paper, is a guarantee of absolute protection given the intrinsic characteristics of the material.

Manufactured with a flash spinning process, Tyvek® fabric is made of continuous and strong high-density polyethylene fibers, with intrinsic barrier properties, without requiring thin layers or additional coatings. This exceptional combination of barrier protection and breathability makes Tyvek® the ideal fabric for packaging and protection. Compared to medical papers, Tyvek® offers an optimal balance between resistance to microbial penetration, tear resistance, puncture resistance and cleanliness. And unlike paper and film for medical use, Tyvek® is compatible with all commonly used sterilization methods, including VHP.

Pharmaclean® by AM Instruments



Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Fecal transplants: The 'super-donor' phenomenon

Fecal transplants have become routine treatment for nasty recurrent diarrheal infections, but trials for other conditions have hit a bum note. Now, scientists have re-examined the evidence.

Time and again, they found one donor whose stool was substantially more likely to lead to clinical improvement than others in the same trial. These 'super-donors' can provide the necessary bacteria to restore gut chemicals that are lacking in illnesses like IBD and diabetes, according to a new review published in Frontiers in Cellular and Infection Microbiology. With Alzheimer's, multiple sclerosis, cancers, asthma, allergies and heart disease all associated with changes to gut bacteria as well, understanding what makes a fecal super donor could make poop the new panacea.

"The last two decades have seen a growing list of medical conditions associated with changes in the microbiome -- bacteria, viruses and fungi, especially in the gut," says senior author Dr Justin O'Sullivan of the University of Auckland.

"In fact, we know already that changes to the gut microbiome can contribute to disease, based on studies in germ-free mice as well as clinical improvement in human patients following restoration of the gut microbiome by transplanting stool from a healthy donor."

While the overall cure rate for recurrent diarrheal infection exceeds 90%, trials of fecal transplantation for other conditions like inflammatory bowel disease exacerbations and type 2 diabetes have had much more mixed results, averaging nearer 20%.

"The pattern of success in these trials demonstrates the existence of 'super-donors', whose stool is particularly likely to influence the host gut and to lead to clinical improvement," explains O'Sullivan.

"We see transplants from super-donors achieve clinical remission rates of perhaps double the remaining average. Our hope is that if we can discover how this happens, then we can improve the success of fecal transplantation and even trial it for new microbiome-associated conditions like Alzheimer's, multiple sclerosis and asthma."

O'Sullivan and colleagues reviewed fecal transplantation trials for clues to the origin of the super-donor phenomenon.

"It is well-known that responders typically exhibit a higher microbial diversity than non-responders. In line with these observations, a larger number of species in the donor stool has been shown to be one of the most significant factors influencing fecal transplantation outcome," O'Sullivan explains.

In particular, super donor stool tends to have high levels of specific 'keystone species'. These are bacteria which produce chemicals whose lack in the host gut contributes to disease.

"In inflammatory bowel disease and diabetes for example, keystone species that are associated with prolonged clinical remission produce butyrate -- a chemical with specialized functions in regulating the immune system and energy metabolism."

The keystone species theory can be tested, of course, by selecting donor stool rich in particular strains -- or by designing 'precision' transplants with a defined mixture of beneficial bacteria, like a probiotic.

"This approach has been applied successfully to prevent complications in a small sample of patients with liver disease. However, this study showed that microbial enrichment in the donor does not completely guarantee enrichment in the recipient."

Clearly, there is more to super-donors than keystone species.

The balance of other bacteria present, and the interactions between them, seems to influence the retention of keystone species.

But digging deeper into stool samples, the researchers have discovered that it matters not only which bacteria are present, but what's present in and around the bacteria.

"For example, the success of fecal transplants has been associated in some studies with the transfer of viruses which infect other gut microbes. Some cases of recurrent diarrheal infection have even been cured with transplants of filtered stool, that has had all the live bacteria filtered out but still contains DNA, viruses and other debris.

"These viruses could affect the survival and metabolic function of transplanted bacteria and other microbes."

Ultimately, O'Sullivan and colleagues acknowledge that super-donors may not fully account for successful fecal transplantation.

"Some fecal transplant failures may be attributable to the gut's immune response to transplanted microbes, possibly stemming from an underlying genetic difference between the donor and the recipient."

"Supporting the transplanted microbiome through diet could also improve success. It has been shown that a rapid change in diet, such as a switch from an animal-based to an exclusively plant-based diet, can alter the composition of the gut microbiota within 24 hours."

They recommend that future fecal transplant trials routinely record information on the genetic background and dietary intake of recipients, so that we can better understand their impact on transplant engraftment and clinical remission.


Brooke C. Wilson, Tommi Vatanen, Wayne S. Cutfield, Justin M. O'Sullivan. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Frontiers in Cellular and Infection Microbiology, 2019; 9 DOI: 10.3389/fcimb.2019.00002
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 16 February 2019

Understanding how bacteria and their viruses interact and evolve

University of Otago research to better understand how bacteria and their viruses interact and evolve will enable future studies to exploit the use of bacteria and their viruses for potential biotechnology and health applications.

Research led by Dr Simon Jackson and Associate Professor Peter Fineran, from the Department of Microbiology and Immunology, investigating the function of bacteria immune systems and what impact they have on the coevolution of bacteria and viruses was published today in a top tier scientific journal, Cell Host and Microbe.

Viruses infecting bacteria are called bacteriophages ("phages" for short) and are the most abundant biological entities on the planet influencing many aspects of our lives and the global ecosystem.

Dr Jackson says the war between phages and bacteria is ever-present and many bacteria protect themselves using immune defences known as CRISPR-Cas systems.

"Research to understand more about the interactions between phages and bacteria, particularly how bacterial CRISPR-Cas immunity functions, is being exploited internationally in many ground-breaking biotechnological applications including gene editing," Dr Jackson explains.

"We think this area of research holds a lot of promise for biotechnology applications and might also be an important consideration for the use of phages to treat infectious diseases.

"For example, because phages kill specific bacteria, they can be used as alternatives to antibiotics to treat some infectious diseases and can even kill antibiotic resistant bacteria."

Bacterial adaptive immunity is similar in concept to human adaptive immunity. Bacteria must first become "vaccinated" against specific phages, which involves the bacteria storing a short snippet of viral DNA, termed a "spacer," used to recognise and defend against future infections.

In a previous study examining how CRISPR-Cas systems acquire spacers, the Otago research team found that often bacteria acquire "incorrect" spacers, known as "slipped spacers." At the time, they did not know whether the incorrect or imprecise slipped spacers were functional.

Associate Professor Fineran, a molecular microbiologist, says their initial observations were surprising and showed these slipped spacers were very efficient at boosting bacterial immunity by stimulating bacteria to acquire extra spacers targeting the same phage. This unexpected role increases immune diversity, which is important for bacteria to protect against the rapidly evolving phages.

"Several groups had previously identified the occurrence of imprecisely acquired or slipped spacers. However, no-one had previously considered whether they were functional or what impact they might have on immunity," Associate Professor Fineran explains.

"By showing they are functional and can provide benefit to bacteria, we have revealed an unexpected complexity to the evolutionary battle between bacteria and phages."

If in the future, researchers can determine how immunity is first gained, they may be able to either prevent or promote it for different applications, Associate Professor Fineran says.

"For example, in the dairy industry for the production of cheese and yoghurt it is beneficial for bacteria to have resistance against phages, whereas if phages are used as antimicrobials, emergence of immunity would be undesirable -- akin to antibiotic resistance."


Simon A. Jackson, Nils Birkholz, Lucía M. Malone, Peter C. Fineran. Imprecise Spacer Acquisition Generates CRISPR-Cas Immune Diversity through Primed Adaptation. Cell Host & Microbe, 2019; DOI: 10.1016/j.chom.2018.12.014

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 15 February 2019

Combatting drug resistant bacteria in intestines with new antibiotic

Clostridium difficile infection (CDI) is a potentially deadly infection in the large intestine most common in people who need to take antibiotics for a long period of time.

Researchers found when doses of a new antibiotic called Ramizol were given to hamsters infected with a lethal dose of the bacteria, a significant proportion of hamsters survived the infection.

In a recent safety study in rats evaluating the effect of repeated exposure of the antibiotic, no rats experienced serious side effects or changes in weight. Forty-eight rats were given a high dose of a new class of antibiotic for 14 days to assess its safety.


Katherine Sibley, Jayson Chen, Lee Koetzner, Odete Mendes, Amy Kimzey, Janice Lansita, Ramiz A. Boulos. A 14-day repeat dose oral gavage range-finding study of a first-in-class CDI investigational antibiotic, in rats. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-018-36690-9

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 14 February 2019

A little squid sheds light on evolution with bacteria

Researchers have sequenced the genome of a little squid to identify unique evolutionary footprints in symbiotic organs, yielding clues about how organs that house bacteria are especially suited for this partnership.

In a new study, an international team of researchers, led by UConn associate professor of molecular and cell biology Spencer Nyholm, sequenced the genome of this little squid to identify unique evolutionary footprints in symbiotic organs, yielding clues about how organs that house bacteria are especially suited for this partnership.

The first squid genome was sequenced by Nyholm, along with Jamie Foster of the University of Florida, Oleg Simakov of the University of Vienna, and Mahdi Belcaid of the University of Hawaii. The team found several surprises, for instance, that the Hawaiian bobtail squid's genome is 1.5 times the size of the human genome.

By comparing the genome of E. scolopes to its cousin, the octopus, the researchers show that the common ancestor of both the octopus and the Hawaiian bobtail squid went through a major genetic makeover, reorganizing and increasing the genome size. This "upgrade" likely gave the cephalopods opportunities for increased complexity, including new organs like the ones that house bacteria.

Many animals have organs that house bacteria. The human gut houses trillions of bacteria that play important roles in digestion, immune function, and overall health. Understanding how these relationships are maintained by identifying genes that help animals cooperate with bacteria lays the groundwork for furthering knowledge of the human body. The Hawaiian bobtail squid is an excellent model for identifying these genes because of its symbiotic relationships with beneficial microbes, and its use by a number of scientists to study communication between bacteria and animals.

The Hawaiian bobtail squid has two different symbiotic organs, and researchers were able to show that each of these took different paths in their evolution. This particular species of squid has a light organ that harbors a light-producing, or bioluminescent, bacterium that enables the squid to cloak itself from predators. At some point in the past, a major "duplication event" occurred that led to repeat copies of genes that normally exist in the eye. These genes allowed the squid to manipulate the light generated by the bacteria.

Another finding was that in the accessory nidamental gland, a female reproductive organ, there was an enrichment of genes that are "orphan genes" or genes that have only been found in the bobtail squid and not in other organisms.


Mahdi Belcaid el al. Symbiotic organs shaped by distinct modes of genome evolution in cephalopods. PNAS, 2019 DOI: 10.1073/pnas.1817322116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 13 February 2019

Antibiotic resistance in the environment linked to fecal pollution

Increased levels of antibiotic resistant bacteria in the environment may have different causes. It could be a consequence of on-site selection from antibiotic residues in the environment, hence promoting the evolution of new forms of resistance. Alternatively, it is simply due contamination by fecal bacteria that often tend to be more resistant than other bacteria. Understanding which explanation is correct is fundamental to manage risks.

A new study shows that "crAssphage," a virus specific to bacteria in human feces, is highly correlated to the abundance of antibiotic resistance genes in environmental samples. This indicates that fecal pollution can largely explain the increase in resistant bacteria often found in human-impacted environments. There was, however, one clear exception where resistance genes were very common also without the presence of the phage -- environments polluted with high levels of antibiotics from manufacturing.

Joakim Larsson, Professor in Environmental Pharmacology at Sahlgrenska Academy, University of Gothenburg, and one of the co-authors, said: "These finding are important as they can inform management of human health risks associated with antibiotic resistant bacteria in the environment. While antibiotic residues is clearly the cause for the exceptionally high levels of resistance found near some manufacturing sites, fecal pollution is probably the explanation in most other places.


Antti Karkman, Katariina Pärnänen, D. G. Joakim Larsson. Fecal pollution can explain antibiotic resistance gene abundances in anthropogenically impacted environments. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-018-07992-3

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Tuesday, 12 February 2019

ISS is not causing bacteria to mutate into dangerous, antibiotic-resistant superbugs

A new study has found that -- despite its seemingly harsh conditions -- the ISS is not causing bacteria to mutate into dangerous, antibiotic-resistant superbugs. The bacteria are instead simply responding, and perhaps evolving, to survive in a stressful environment.
A new Northwestern University study has found that -- despite its seemingly harsh conditions -- the ISS is not causing bacteria to mutate into dangerous, antibiotic-resistant superbugs.

While the team found that the bacteria isolated from the ISS did contain different genes than their Earthling counterparts, those genes did not make the bacteria more detrimental to human health. The bacteria are instead simply responding, and perhaps evolving, to survive in a stressful environment.
"There has been a lot of speculation about radiation, microgravity and the lack of ventilation and how that might affect living organisms, including bacteria," said Northwestern's Erica Hartmann, who led the study. "These are stressful, harsh conditions. Does the environment select for superbugs because they have an advantage? The answer appears to be 'no.'"

The ISS houses thousands of different microbes, which have traveled into space either on astronauts or in cargo. The National Center for Biotechnology Information maintains a publicly available database, containing the genomic analyses of many of bacteria isolated from the ISS. Hartmann's team used that data to compare the strains of Staphylococcus aureus and Bacillus cereus on the ISS to those on Earth.

Found on human skin, S. aureus contains the tough-to-treat MRSA strain. B. cereus lives in soil and has fewer implications for human health.

"Bacteria that live on skin are very happy there," Hartmann said. "Your skin is warm and has certain oils and organic chemicals that bacteria really like. When you shed those bacteria, they find themselves living in a very different environment. A building's surface is cold and barren, which is extremely stressful for certain bacteria."

To adapt to living on surfaces, the bacteria containing advantageous genes are selected for or they mutate. For those living on the ISS, these genes potentially helped the bacteria respond to stress, so they could eat, grow and function in a harsh environment.


Ryan A. Blaustein, Alexander G. McFarland, Sarah Ben Maamar, Alberto Lopez, Sarah Castro-Wallace, Erica M. Hartmann. Pangenomic Approach To Understanding Microbial Adaptations within a Model Built Environment, the International Space Station, Relative to Human Hosts and Soil. mSystems, 2019; 4 (1) DOI: 10.1128/mSystems.00281-18

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 11 February 2019

Burkholderia cepacia complex: origins, risks and test methods

Burkholderia cepacia complex (BCC) isolates are causes of healthcare-associated infection, especially in relation to contamination of aqueous inhalers and some intravenously administered products. The bacterial species can cause opportunistic infections in vulnerable individuals, especially those with cystic fibrosis (CF).
The organisms can cause pneumonia in immunocompromised individuals (especially when introduced into the air passages of a susceptible population). In the past decade, organisms that fall within the BCC grouping have been identified as potentially ‘objectionable’ within the pharmaceutical manufacturing environment; especially given the connection between such organisms and non-sterile products and the target patient population that includes the young, elderly and immunocompromised.

This article reviews the origins of Burkholderia cepacia in pharmaceutical facilities and the particular risks that it poses to patient populations. The article also considers the optimal test methods to use to screen for the organism group.

The reference is:

Sandle, T. (2018) Burkholderia cepacia complex: review of origins, risks and test methodologies, European Pharmaceutical Review, 23 (5): 30-32

Foe a copy please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 10 February 2019

RNA Sequencing Market Benefits from Advancements in Sequencing Technology

An approach to transcriptome profiling, RNA sequencing is a widely used tool in genetics and genomics that can analyze the sequence and quantity of RNA in a sample using next-generation sequencing (NGS). The technique helps one investigate and discover the transcriptome (the sum of all the messenger RNA molecules expressed from genes of an organism), which gets information about the functions of genes as to which genes are turned on in a cell, when they are activated or turned off, and what their level of expression is, and so on. All this information allows scientists to comprehend a cell’s biology and identify any alteration that may indicate disease. It also assists in the study of complex events such as alternative splicing and polyadenylation.

A guest post by Sunny Yadav

The RNA sequencing market is witnessing a fast growth in recent years, owing to the growing incidence of genetic disorders, advancements in sequencing technology, increasing number of RNA-seq grants, increase in acceptance of NGS technology, and a growing number of partnerships and collaborations. Moreover, government initiatives in population sequencing and emerging markets such as China & India offer significant growth opportunities for the growth of the industry. Nonetheless, lack of skilled professionals and problems associated with storage of sequencing data restrain the market growth.

Several developments took place in the field recently. A team of scientists from the University of Chicago Medicine (UChicago) came up with a novel high-throughput RNA sequencing strategy with the aim of studying the gut microbiome. Researchers at the Stanford lab of Stephen Quake are adopting a single cell RNA sequencing (scRNA-seq) in order to provide insights into food allergies and antibodies that cause them. QIAGEN, a Netherlands-based provider of sample and assay technologies for molecular diagnostics, launched a technology which allows faster and simpler library preparation for RNA sequencing.

UChicago Scientists Develop Revolutionary Strategy

Researchers at the University of Chicago recently discovered an RNA sequencing strategy for studying the activity of the gut microbiome. The strategy allows scientists to understand how tRNA changes dynamically within microbiomes and gives insights into how naturally occurring microbiomes respond to environmental changes such as temperature variation or changes in nutrient availability. The team of scientists created new tools to study transfer RNA (tRNA) in mouse gut microbiomes. According to the study, tRNA sequencing was applied to samples from the gut microbiome of mice that were on a high-fat or low-fat diet. New tools were employed to create a set of tRNA molecules from the samples. The bacteria from where the tRNA molecules originated were tracked and the post-transcriptional modifications that occurred were identified and measured. The tools used can identify two modifications in a high-throughput sequencing and analysis workflow. The level of one of the modifications was found increased in gut microbiomes of mice in a high-fat diet. For the first time scientists could notice a change in the modification level in tRNA in any microbiome.

QIAGEN Introduces a Breakthrough Technology for RNA Sequencing

QIAGEN unveiled a novel technology which facilitates faster and simpler library preparation for RNA sequencing. A prime component of this technology, the QIAseq FastSelect RNA Removal Kit allows scientists to target the types of RNA that are unrelated to their research and eliminate them from RNA-seq libraries for next-generation sequencing (NGS). According to Dr. Thomas Schweins, Senior Vice President of QIAGEN’s Life Sciences Business Area, the QIAseq FastSelect RNA Removal Kit enables faster removal of RNA types from a given sample, thus allowing scientists to achieve quality and reproducible RNA sequencing results. It also helps reduce time and cost. The kit helps to simplify and accelerate the process of RNA removal.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

New microbial strains in the human fecal community

Using a unique bioinformatics technique, researchers have detected the emergence of new strains of microbes in the human fecal microbiota after obesity surgery. These new strains emerged after surgical disruption of the stomach and upper small intestine. In contrast, the researchers found that strains of the human gut fecal microbiota resembled those found pre-surgery following surgery in the colon.

The ability of the informatics technique to discriminate among individual strains of the same species advances analysis of the human gut microbiota and how surgery may alter the microbial community. The human microbiota largely consists of 500 to 1,000 bacterial species that have a mainly beneficial influence on human health, including modulation of the immune system and influences on host metabolism and organ development. Previous studies of the microbiota have been able to determine changes in the relative abundance of various species after obesity surgery, but they could not discern whether this could be due to the replacement of one strain of a particular species by another strain of that same species.

"Our results show that, when you change the upper GI tract with obesity surgery, you also change the gut environment, resulting in the emergence of new strains of microbes," said Casey Morrow, Ph.D., leader of the research team and professor emeritus in UAB's Department of Cell, Developmental and Integrative Biology. "In the microbial competition for nutrients and space in the GI tract, the winners are new strains that are more competitive in the new GI tract environment."


Ranjit Kumar, Jayleen Grams, Daniel I. Chu, David K. Crossman, Richard Stahl, Peter Eipers, Kelly Goldsmith, Michael Crowley, Elliot J. Lefkowitz, Casey D. Morrow. New microbe genomic variants in patients fecal community following surgical disruption of the upper human gastrointestinal tract. Human Microbiome Journal, 2018; 10: 37 DOI: 10.1016/j.humic.2018.10.002

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Saturday, 9 February 2019

New strategy to curtail spread of antibiotic resistance

Researchers at Washington University School of Medicine in St. Louis have figured out a key step in the transmission of antibiotic resistance from one Acinetobacter bacterium to another, insight that sheds light on how antibiotic resistance spreads through a hospital or community. This could open up a new strategy to safeguard our ability to treat bacterial infections with antibiotics. The research indicates that the effectiveness of current antibiotics may be somewhat preserved by curtailing the spread of antibiotic-resistance genes.

Spotless surfaces in hospitals can hide bacteria that rarely cause problems for healthy people but pose a serious threat to people with weakened immune systems. Acinetobacter baumannii causes life-threatening lung and bloodstream infections in hospitalized people. Such infections are among the most difficult to treat because these bacteria have evolved to withstand most antibiotics.

Acinetobacter strains carry the genetic blueprints for drug resistance on small loops of DNA called plasmids that come in two sizes. Big plasmids, which are prone to accumulating ever more antibiotic-resistance genes, carry the genetic instructions to build a needle-like appendage to insert copies of themselves into nearby bacteria. Small plasmids, which contain resistance genes against a single but important group of antibiotics known as carbapenems, lack their own distribution tools so they invade new bacteria by tagging along with the large plasmids.

The plasmids' reproductive strategy requires close contact between two bacteria. But that raises a question: How do two bacteria ever get near enough to transmit plasmids to each other? Most Acinetobacter guard against strangers with a system that injects lethal proteins into any unrelated bacteria that approach too closely, thus reducing the changes of spreading antibiotic-resistance genes.

The researchers found that plasmids disable bacteria's self-defense systems so that plasmids can inject copies of themselves into neighboring bacteria, conferring drug resistance on the unwitting bacterial neighbors. By forcing the bacteria in which they reside to lay down their weapons, the plasmid ensures that nearby bacteria aren't killed before the plasmids can infect them. The researchers found that mutating plasmids so they could not interfere with the bacteria's defenses - or mutating the bacteria so the defenses could not be lowered -- prevented plasmids from spreading.

These findings provide a novel opening to interrupt the spread of drug resistance, the researchers said. The genes involved have been identified. Now researchers have to find compounds that prevent plasmids from disrupting bacterial-defense systems.


Gisela Di Venanzio, Ki Hwan Moon, Brent S. Weber, Juvenal Lopez, Pek Man Ly, Robert F. Potter, Gautam Dantas, Mario F. Feldman. Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination. Proceedings of the National Academy of Sciences, 2019; 201812557 DOI: 10.1073/pnas.1812557116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Friday, 8 February 2019

Bacteria help discover human cancer-causing proteins

A team led by researchers at Baylor College of Medicine and the University of Texas at Austin has applied an unconventional approach that used bacteria to discover human proteins that can lead to DNA damage and promote cancer. Reported in the journal Cell, the study also proposes biological mechanisms by which these proteins can cause damage to DNA, opening possibilities for future cancer treatments.

Mutations that cause cancer can be the result of DNA damage. External factors such as tobacco smoke and sunlight can damage DNA, but most DNA damage seems to result from events that occur within cells and is mediated by cellular components, including proteins. Despite the importance of these events, they have not been studied extensively.

To uncover these DNA "damage-up" proteins, the researchers took an unconventional approach. They searched for proteins that promote DNA damage in human cells by looking at proteins that, when overproduced, would cause DNA damage in the bacterium E. coli.

The researchers genetically modified bacteria so they would fluoresce red when DNA was damaged. Then, they overexpressed each of the 4,000 genes present in E coli individually and determined which ones made bacteria glow red.


Jun Xia, Li-Ya Chiu, Ralf B. Nehring, et al. Bacteria-to-Human Protein Networks Reveal Origins of Endogenous DNA Damage. Cell, 2019; 176 (1-2): 127 DOI: 10.1016/j.cell.2018.12.008

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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