Thursday, 23 March 2017

New TB drug candidates developed from soil bacteria

A new treatment for tuberculosis (TB) is set to be developed using compounds derived from bacteria that live in soil -- according an international collaboration of researchers, including the University of Warwick.

The group looked at soil bacteria compounds, known to effectively prevent other bacteria growing around them. Using synthetic chemistry, the researchers were able to recreate these compounds with structural variations, turning them into more potent chemical analogues.

When tested in a containment laboratory, these analogues proved to be effective killers of Mycobacterium tuberculosis -- the bacterium which causes TB.

These chemicals target an enzyme in Mycobacterium tuberculosis called MraY, which catalyses a crucial step in building the cell wall around a bacterium. Attacking this part -- a potential 'Achilles' heel' of the bacterium -- provided an essential pathway for the antibacterial compounds to attack and destroy TB strains.

For further details see:

Anh T. Tran, Emma E. Watson, Venugopal Pujari, Trent Conroy, Luke J. Dowman, Andrew M. Giltrap, Angel Pang, Weng Ruh Wong, Roger G. Linington, Sebabrata Mahapatra, Jessica Saunders, Susan A. Charman, Nicholas P. West, Timothy D. H. Bugg, Julie Tod, Christopher G. Dowson, David I. Roper, Dean C. Crick, Warwick J. Britton, Richard J. Payne. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis. Nature Communications, 2017; 8: 14414 DOI: 10.1038/ncomms14414

Best buy:

Posted by Dr. Tim Sandle

Wednesday, 22 March 2017

10 Healthy Eating Tips for the Student

College students must know how to maintain their body healthily and strong. Their food diet should be well-planned, and they should take their food in time. Eating is compulsory for all of us. But for students, it is more than necessary. They must choose healthy foods for their mental health as well as their physical health. There are 10 Healthy Eating Tips for Student.

Guest post by Anthony J Maldonado

1- Never skip breakfast

Breakfasts are necessary to make your day awesome. It indeed helps in the study too. If you take breakfast, you will have a healthy mood. If you miss it somehow, take it whenever you have time. It assists you to focus on your study. It kicks starts your metabolism. Your metabolism will start slow if you miss your breakfast. You’ll feel a lot hungry and might get enticed to eat a larger meal. In short, your metabolism will get affected.
2- Take snacks at regular intervals

Take easy snacks when you study. In every 3 hours, take light foods. Don’t skip your meals because it hampers your body weight by making you obese or overweight. You can take apples, bananas, applesauce, etc. as easy snacks.

3- Maintain your class schedules

As a student, you must know how to manage your class schedules. You need to find out when your English tuition and where you should have to go for private tuition. In this way, you can routine your diet also. You can plan what to eat and what to not.

4- Avoid empty calories

Students often hang out with friends. They get tempted to junk foods. Try avoiding empty calories as it is harmful to your health. They contain high calories but little nutrition. Foods such as cakes, cookies, pastries, donuts, fat cheese, bacon, sausages, ice creams, etc. are less useful for human body.

5- Drink lots of water

Every day take at least 2litres of water. It aids your health a lot. It helps to manage your body fluids as your body is composed of about 60% of water. It controls calories and energizes body muscles also. It helps your kidney because if you take little water, you’ll be at high risk for a kidney stone. It removes toxins and promotes weight-loss.

6- Physical Exercise

Every day do physical exercise to build yourself fit and healthy. Schedule your time for physical exercise. It burns your calories and makes your body strong and stout. It combats health conditions and diseases. It also helps you to have a better sleep. When you’re at the college, try visiting the gym center. There you can try attending light body work to keep your body smooth. Every day if you continue to do so, you’ll have a sizzling healthy body. Physical exercise such as swimming, cricket, running, etc. can be useful to you too.

7. Have a sensible diet

Diet is a significant part of your health. Try maintaining it correctly. Include omelet’s, casseroles, soups, pasta, lentils and rice in your food plan. Try fresh herbs and spices in your meals. A healthy eating habit is behind the success of a healthy body. A sensible diet should contain protein, fats, carbohydrates and fiber so that the body can be maintained smoothly. Overall, the balance of food is vital to keep your body fit and active.

8. Maintain hygiene

Keep your kitchen and kitchenware clean. Always wash hands before you prepare food. It does not allow the other person to get the germs from you. Maintain hygiene in the fridge as well. Make sure to have your fridge temperature below 5C.Hygiene is vital in social life too. Lack of hygiene is a sign of offensive behavior and illness.

9.  Do food-shopping

Never buy food from one shop only. Try observing the market a lot to know the real price. It will allow you to know what to buy and from where to buy. You will also get an idea on how much you cost for food. In this way, you can limit your expenses and focus on your health too.

10. Look for available cafeteria

Be like a nutritionist. Look for open cafeteria around your area where you can have healthy food. You can change your taste in cheap rate. You can spend quality time too with your friends at the cafeteria.

Tuesday, 21 March 2017

TB Alliance Calls on WHO to Add Tuberculosis to List of Critical Group of Bacteria

TB Alliance and the broader TB community urge that the World Health Organization (WHO) add Mycobacterium tuberculosis to the critical group within the list of drug-resistant bacteria identified as urgent priorities for research and development.

“The absence of TB from this list is shocking,” said Mel Spigelman, President and CEO of TB Alliance. “The effort to develop new drugs to cure TB has always been chronically underfunded despite the disease’s impact.” TB is the world's deadliest infectious disease, killing 1.8 million people each year.

TB patients urgently need new and better antibiotics. Treatment for drug-resistant TB is long, toxic, complicated, and expensive. It can consist of more than two years of a dozen or more pills per day, along with six months of daily injections. And for those unfortunate enough to have extensively resistant TB, even if they take every one of those 20,000 toxic pills and hundreds of injections, they will still have less than a one in three chance of survival. Put simply, TB has evolved at a speed that outpaces our underfunded research community.

This year alone, approximately half a million people will develop drug-resistant TB. Multidrug-resistant TB (MDR-TB) is caused by TB bacteria that is resistant to at least isoniazid and rifampin, the two most potent TB drugs. Less than 20 percent of people with MDR-TB receive treatment; of that small fraction, about half are cured. To place the drug resistant TB situation in perspective, patients with Ebola, for whom there is no available drug therapy, have the same chances of survival that patients with drug-resistant TB patients have, accessing today’s available medicines. MDR-TB is also the most contagious of all the pathogens noted on the WHO’s list, spreading readily from person to person, and is especially dangerous to children, people with HIV, and other vulnerable populations.

About 29 percent of deaths caused by antimicrobial infections are due to drug-resistant TB, according to the US Centers for Disease Control and Prevention. MDR-TB could cost the world $16.7 trillion by 2050, according to a study commissioned by the UK government. Last year's high-level meeting on AMR at the UN General Assembly affirmed that TB is critical to the antimicrobial resistance (AMR) agenda.

New tools, including vaccines, diagnostics, and treatments, cannot be developed without adequate resources, and the global TB community faces significant underfunding. The WHO’s 2011-2015 Global Plan to Stop TB saw a five-year funding deficit of $2.4 billion in drug R&D, and 2015 saw the biggest decline in R&D funding for TB in over a decade. Even efforts to treat and prevent the disease are underfunded by almost $2 billion, according to the WHO.

Drug resistant TB is an urgent and critical priority. Without more attention and new antibiotics, the disease will continue to wreak havoc among the world’s poorest communities. It is not enough to say that TB is being addressed by other health programs; drug resistant TB is the biggest global threat in AMR and it must be recognized as such, especially by the WHO. The absence of TB from the WHO list is an irresponsible public health statement, sending the wrong message about global health priorities.

WHO did issue a follow-up release affirming the critical need for R&D of new antibiotics to tackle drug-resistant tuberculosis. This effort, however, should not be separate from efforts to address other drug-resistant pathogens.

Every global effort to address the burgeoning AMR emergency must include TB, and the WHO should be taking a leadership role in this effort, starting with the inclusion of TB on the new WHO list of priority pathogens.

Monday, 20 March 2017

National Poison Prevention Week

In recognition of National Poison Prevention Week (March 19-25), the National Capital Poison Center urges all parents to take 2 minutes to learn how to prevent and respond to a poison emergency. More than a million poison exposures occur every year in U.S. children younger than 6 years.

“There are two ways to get free, confidential, expert help if a poisoning occurs”, says Dr. Toby Litovitz, MD, Director of the National Capital Poison Center.

There’s no need to memorize that contact info. The National Capital Poison Center provides a new “text-to-save” functionality. Text “poison” to 484848 (don’t type the quotes) to save the contact info directly to your smart phone (standard text messaging rates apply).

You can also download the vcard at Litovitz: “Share that vcard info with babysitters, grandparents, family and friends“.

“Here are 6 important ways to keep your home poison safe”, continues Dr. Litovitz:
  1. Up, up and away! Keep medications and poisonous household products out of your child’s sight and reach. Locked up is best.
  2. Avoid container transfer. Some of the most devastating poisonings occur when toxic products are poured into food or beverage containers, then mistaken for food or drink.
  3. Read the label and follow the directions. Misusing products has dire consequences.
  4. Use child-resistant packaging. It’s not child-proof, but so much better than nothing. Sorry it’s inconvenient, but using it could save a life.
  5. Keep button batteries away from children. Swallowed batteries can burn through your child’s esophagus and cause permanent injury or even death.
  6. Keep laundry pods out of your child’s reach. They are as toxic as they are colorful and squishy.
Need more prevention reminders? Text “poison” to 22828 to subscribe to The Poison Post® for free, quarterly poison prevention updates by email. Or go to for more tips.

About the National Capital Poison Center

The National Capital Poison Center is an independent, not-for-profit organization and an accredited poison center. Its nurse and pharmacist Certified Specialists in Poison Information provide 24/7 telephone guidance for poison emergencies, free of charge. It also provides online guidance for poison emergencies through the webPOISONCONTROL® tool, health professional education in toxicology, and poison prevention education. Service focuses on the metro DC area with a national scope for projects such as webPOISONCONTROL, the National Battery Ingestion Hotline (202-625-3333), and The Poison Post®.

Sunday, 19 March 2017

Which Medicine For Ed Has The Lowest Number Of Side Effects?

Erectile dysfunction (ED) is pretty common among men with almost half of men between the ages 40 to 70 have some kind of erectile problems.  The Journal of the American Medical Association reported that
7 percent of men aged 18 to 29 and 9 percent of men aged 30 to 39 have problems to achieve orgasm. After taking an ED drugs, 70 percent of healthy men have reported in achieving an erection sufficient for intercourse.

Guest post by Jennifer Lia.

How Do Erectile Dysfunction Medicines Or Drugs Work?

Erectile dysfunction medicines or drugs such as Viagra, Levitra, Cenforce 100mg, Stendra, Cialis, Kamagra 100mg, etc., work by relaxing the tight blood vessels in the penis. This allows more blood to enter the penis which results in an erection. These pills are effective to more than two-thirds of men with erectile dysfunction (ED).  ED drugs also reduce the recovery period between sexual intercourses. It is extremely helpful for men who are suffering from premature ejaculation.

Do Erectile Dysfunction (ED) Drugs Have Side Effects?

Every drug has side effects. Viagra, Levitra, Cenforce 100mg, Stendra, Cialis, Kamagra 100mg, etc., might cause headaches, dizziness, indigestion or a runny nose. However, most men have reported that they hardly experienced any side effects, and even if they did, they didn’t mind them. If you want to reduce the risk of potential side effects, start initially with a small dose. Up your dosage slowly if it works. 

If you’ve erectile dysfunction, at best you might have a nasal congestion, says Dr. Harry Fisch of Weill Cornell Medical College and New York-Presbyterian Hospital. Meanwhile, don’t worry you’ll get addicted or dependent on ED drugs. Most erectile dysfunction (ED) drugs aren’t addictive or cause dependencies, according to Dr. Michael Eisenberg of Stanford University.

Which Erectile Dysfunction Drug Comes With The Least Side Effects?

Sildenafil or commonly known as Viagra is prescribed by most doctors to men suffering from erectile dysfunctions. Viagra has have been in the market for a very long time, and its side effects are well-known and addressed. Meanwhile, there is new ED drug, Avanafil or Stendra, which is said to have the least side effects all other ED drugs.

What Are The Causes Of Erectile Dysfunction?

Most doctors have blamed diabetes, hypertension, high cholesterol and various heart diseases for erectile dysfunction. Men suffering from these ailments restrict blood flow in an extreme way to the penis, which makes it harder for these men to have a strong and long-lasting erection, says Dr. Fisch.

How to Have Better Erections without Taking ED Drugs?

You can have better erections without taking any erectile dysfunction (ED) drugs. Here’s how:
  • Quit smoking. Smoking restricts the blood vessels from relaxing, which is vital if you want to have erections. Stop smoking is much better than taking ED drugs. 
  • Shed excess body weight, and do anything to keep your blood pressure in check. If you lose weight, you can keep your blood pressure under control. With Hypertension, the blood vessels lose its ability to dilate properly. 
  • Cut back on alcoholic beverages or drink in moderation. Your sex drive may get a boost if you drink alcohol, but will decrease your performance, says Dr. Fisch 
  • Try to have sex in the morning instead of night. You can have better erections at that time as your testosterone levels increases in the morning.
5.       Check out on medications that cause you some problems to have an erection. For example, avoid taking a nasal decongestant like Sudafed, antidepressants such as Prozac, or anti-hypertension medicines like thiazines before sexual intercourse.

New way to classify viruses based on structure

Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support a classification system for viruses based on viral structure.

The team developed a new highly-sensitive computational prototype tool, and used it to detect similarities in the genetic code of viruses with similar outer structures, that conventional tools have failed to detect, suggesting that they share a common ancestor. This is not what would have been expected if similarities in the structure of viruses were due to similar environmental pressures -- a phenomenon known as convergence.

The results, published in the Journal of Virology, suggest that viral structure could provide a means of categorizing viruses with their close relatives -- a potentially superior approach to current classification systems. Application of this new structure-based classification system could make it easier to identify and treat newly emerging viruses that cannot easily be classified with existing classification systems.

Viruses are notoriously difficult to classify due to their enormous diversity, high rates of change and tendency to exchange genetic material. They challenge the very concept of a clear distinction between the living and the dead, with many characteristics resembling those of living things, but lacking the ability to reproduce themselves, without the help of a host cell. As such, they do not fit neatly into the established biological classification system for cellular organisms.

Existing classification systems are imperfect and often lead to very similar viruses being categorized as entirely different entities. These systems are also unable to account for the fact that viruses are constantly changing.

If scientists could identify something that viruses are unable to change, it could provide a basis for a more meaningful approach to classification and enable the scientific community to tackle emerging viruses, such as HIV, SARS coronavirus and Zika virus, more easily.

Previously observed similarities between the protein shell, or 'capsid', of viruses -- that encloses and protects the genetic material -- provide a basis for a classification system based on capsid structure, as previously proposed by Prof. Bamford. The few ways in which viruses package themselves are very similar, even between viruses that are likely to have had their common relative more than a billion years ago. Whether this conservation is due to convergence or common descent has been disputed.

For a classification system based on virus capsid structure to be meaningful, the amino acids that provide the building blocks of the capsid proteins should be similar in related viruses. A seeming lack of sufficient amino acid sequence similarity picked up by conventional sequence analysis tools previously undermined capsid structure as a viable way to classify viruses.

Using ideas from mathematics and computer science, Professor Sinclair from OIST's Mathematical Biology Unit worked with scientists at the University of Helsinki to reinvestigate whether the structure-based classification for viral capsids is in fact supported by previously undetected sequence similarity.


Robert M. Sinclair, Janne J. Ravantti, Dennis H. Bamford. Nucleic and amino acid sequences support structure-based viral classification. Journal of Virology, 2017; JVI.02275-16 DOI: 10.1128/JVI.02275-16

Posted by Dr. Tim Sandle

Saturday, 18 March 2017

Novel genetic switch boosts bacteria cells' production of useful chemicals

MIT chemical engineers have designed a novel genetic switch that allows them to dramatically boost bacteria's production of useful chemicals by shutting down competing metabolic pathways in the cells.

Researchers have been trying to engineer microbes to generate more complex products, including pharmaceuticals and biofuels. This usually requires adding several genes encoding the enzymes that catalyze each step of the overall synthesis.

In many cases, this approach also requires shutting down competing pathways that already exist in the cell. However, the timing of this shutdown is important because if the competing pathway is necessary for cell growth, turning it off limits the population size, and the bacteria won't produce enough of the desired compound.

A laboratory has engineered E. coli to produce glucaric acid by adding three genes -- one each from yeast, mice, and a strain of bacteria called Pseudomonas syringae. Using these three genes, bacteria can transform a compound called glucose-6-phosphate into glucaric acid. However, glucose-6-phosphate is also an intermediate in a critical metabolic pathway that breaks down glucose and converts it into the energy cells need to grow and reproduce.

To generate large quantities of glucaric acid, the researchers had to come up with a way to shut down the glucose-breakdown pathway, allowing glucose-6-phosphate to be diverted into their alternative metabolic pathway. However, they had to carefully time the shutdown so that the cell population would be large enough to produce a substantial amount of glucaric acid. More importantly, they wanted to do so without adding any new chemicals or changing the process conditions in any way.

In addition to adding the genes for glucaric acid production, the researchers engineered each cell to produce a protein that synthesizes a small molecule called AHL. The cells secrete this molecule into their environment, and when the concentration surrounding the cells gets to a certain point, it activates a switch that makes all of the cells stop producing an enzyme called phosphofructokinase (Pfk), which is part of the glucose breakdown pathway. With this enzyme turned off, glucose-6-phosphate accumulates and gets diverted into the alternative pathway that produces glucaric acid. By constructing a library of cells that produce AHL at different rates, the researchers could identify the best time to trigger shutdown of Pfk.

Using this switch, the researchers were able to generate about 0.8 grams of glucaric acid per liter of the bacterial mixture, while cells that were engineered to produce glucaric acid but did not have the metabolic switch produced hardly any.

To demonstrate this versatility, the researchers tested their approach with a metabolic pathway that produces a molecule called shikimate, which is a precursor to several different amino acids and is also an ingredient in some drugs including the influenza drug Tamiflu. They used the AHL quorum-sensing molecule to shut off an enzyme that moves shikimate further along in the amino acid synthesis pathway, allowing shikimate to build up in the cells. Without the switch, the cells could not accumulate any shikimate.


Apoorv Gupta, Irene M Brockman Reizman, Christopher R Reisch, Kristala L J Prather. Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit. Nature Biotechnology, 2017; DOI: 10.1038/nbt.3796

Posted by Dr. Tim Sandle

Friday, 17 March 2017

Gut inflammation controlled by changing bacterial balance

Numerous human diseases, including inflammatory bowel disease, diabetes and autism spectrum disorders have been linked to abnormal gut microbial communities, or microbiomes, but an open question is whether these altered microbiomes are drivers of disease.
A new study at the University of Oregon, led by postdoctoral fellow Annah Rolig, took aim at that question with experiments in zebrafish to dissect whether changes in the abundance of certain gut bacteria can cause intestinal inflammation.

The researchers successfully tracked how gut bacterial abundances influenced inflammation. Fish with intestinal inflammation had a larger abundance of a subset of bacteria that appeared to be pro-inflammatory, which they confirmed by dosing the fish with one of these bacteria and finding that it increased the severity of disease symptoms.

They also found a subset of bacteria that was depleted in the inflamed intestines, but present in the mutant fish that remained disease-free. Dosing the fish with a strain of these depleted bacteria ameliorated the disease. Finally, they showed that they could cure the inflammation by transplanting gut neurons from healthy fish into the diseased fish.

These studies demonstrate that inflammatory intestinal pathologies, such as Hirschsprung-associated enterocolitis or inflammatory bowel disease, can be explained as an overgrowth of certain pro-inflammatory groups of bacteria or a loss of anti-inflammatory bacteria, said Judith Eisen, a professor of biology and an expert on gut neurons in zebrafish.

Identifying the bacteria that drive and protect against disease is the first step toward developing microbial interventions and therapies.

For further details see:

Annah S. Rolig, Erika K. Mittge, Julia Ganz, Josh V. Troll, Ellie Melancon, Travis J. Wiles, Kristin Alligood, W. Zac Stephens, Judith S. Eisen, Karen Guillemin. The enteric nervous system promotes intestinal health by constraining microbiota composition. PLOS Biology, February 2017 DOI: 10.1371/journal.pbio.2000689

Posted by Dr. Tim Sandle

Thursday, 16 March 2017

Commonly used pain relievers have added benefit of fighting bacterial infection

Some commonly used drugs that combat aches and pains, fever, and inflammation are also thought to have the ability to kill bacteria. New research appearing online on March 13 in the Cell Press journal Chemistry & Biology reveals that these drugs, better known as NSAIDs, act on bacteria in a way that is fundamentally different from current antibiotics. The discovery could open up new strategies for fighting drug-resistant infections and "superbugs."

"We discovered that some anti-inflammatory drugs used in human and veterinary medicine have weak antibiotic activity and that they exert this secondary activity by preventing bacteria from copying their DNA, which they need to do in order to multiply," explains senior author Dr. Aaron Oakley of the University of Wollongong, in Australia. The researchers analyzed three NSAIDs: bromofenac, carprofen, and vedaprofen. The more commonly known NSAIDs, which include aspirin, ibuprofen, and naproxen, were not tested.

Dr. Oakley and his team identified that anti-inflammatory drugs bind to and inhibit a specific protein in bacteria called the DNA clamp. The DNA clamp, which is conserved across bacterial species, is part of an enzyme that synthesizes DNA molecules from their nucleotide building blocks.

The discovery comes at a time when there is a pressing need for new classes of antibiotics. "The fact that the bacteria-killing effect of the anti-inflammatory drugs is different from conventional drugs means that the NSAIDS could be developed into new kinds of antibiotics that are effective against so-called superbugs," says Dr. Oakley. "This is important because the superbugs have become resistant to many -- and in some cases most -- of the available antibiotics."


Yin et al. DNA Replication is the Target for the Antibacterial Effects of Non-Steroidal Anti-Inflammatory Drugs. Chemistry & Biology

Posted by Dr. Tim Sandle

Wednesday, 15 March 2017

Rainbow dyes add greater precision to fight against 'superbugs'

The discovery, made possible through a revolutionary method used to color bacterial cell walls developed at IU, is an important step forward in research on bacterial growth and could inform efforts to develop drugs that combat antibiotic-resistant bacteria.

Globally, antibiotic-resistant bacteria, or "superbugs," pose a major risk to human health. The World Health Organization estimates about 480,000 people develop multi-drug resistant tuberculosis each year. In the U.S., the Centers for Disease Control estimates 1 in 4 hospital-acquired infections in long-term patients are caused by six major strains of the bugs.

"This is the first study to 'connect the dots' between each part of the cell involved in bacterial cellular division," said Yves Brun, the Clyde Culbertson Professor of Biology in the IU Bloomington College of Arts and Sciences' Department of Biology, who is an author on the study. "We've finally closed the circle on this mechanism and opened the door to more precise methods in the fight against antibiotic-resistant bacteria.

"If you understand how an engine works, you can shut it down by removing a single part," Brun said. "You no longer need to throw a hammer into the works to destroy it."

Early antibiotics like penicillin function like a hammer: a blunt instrument that destroys the bacterial cell in the midst of division by tricking cell wall-making enzymes called penicillin-binding proteins, or PBPs, into binding to the drug rather than the building blocks of the cell walls, causing the walls to breach and the cells to explode.

Other parts of the cell that drive bacterial division include cytoskeletal proteins, called FtsA and FtsZ, which form skeleton-like fibers inside cells to direct construction of the cell wall. All three elements must coordinate to build a cell wall in the middle of the cell to ensure the material inside doesn't escape after it splits in half.

The fact that these three parts of the cell play a role in cellular division is known, but the new study is the first to show exactly how they coordinate. Essentially, Brun said, FtsZ acts as a "foreman" that directs the movement of PBP "workers" as they construct a cell wall.

The researchers were able to detect the action with high-tech, multi-colored dyes called fluorescent D-amino acids, or FDAAs, discovered five years ago in the lab of Michael VanNieuwenhze, professor in the IU Bloomington College of Arts and Sciences' Department of Chemistry, who is a co-author on the study.

"The application of different colors of these dyes during the cell wall construction process revealed a 'bull's-eye pattern,' indicating the circular wall is built from the outer edge of the cell inward to the center," VanNieuwenhze said.

The study also solves another mystery: How do FtsZ molecules build the wall? The researchers found that FtsZ -- which is arrayed in a biochemical chain called a filament -- constantly loses a molecule at one end and gains a molecule at the other end, resulting in a circular motion around the cell's edge described as "treadmilling."

IU researchers chemically labeled the cells for analysis. Harvard scientists performed the experiments that showed the motion of the FtsZ and PBP proteins inside the cell.

The subject of a U.S. patent filed by the IU Research and Technology Corp., FDAA dyes have played an important part in dozens of other scientific papers on bacteria since 2012. VanNieuwenhze's lab also has about 50 material transfer agreements with researchers across the globe to provide access to the tool.

The creation of the dyes at IU was led by Erkin Kuru, a former Ph.D. student in the labs of VanNieuwenhze and Brun who is currently a research fellow at Harvard. Kuru and Yen-Pang Hsu, a IU Ph.D. student also in the labs of VanNieuwenhze and Brun, are co-authors on the study.

"This is the first time we've been able to observe cell division as a dynamic process -- that is, a process occurring over time," Kuru said. "This wasn't possible before since we lacked the tools to see it."

Hsu added that "the visualization of these cell structures is no small task when you consider the organism that contains them is less than a micrometer -- or one-thousand of a millimeter -- wide. We wouldn't have been able to measure the fluorescent patterns in these cells without the technology at the IU Light Microscopy Imaging Center."


Alexandre W. Bisson-Filho, Yen-Pang Hsu, Georgia R. Squyres, Erkin Kuru, Fabai Wu, Calum Jukes, Yingjie Sun, Cees Dekker, Seamus Holden, Michael S. VanNieuwenhze, Yves V. Brun, Ethan C. Garner. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science, 2017; 355 (6326): 739 DOI: 10.1126/science.aak9973

Posted by Dr. Tim Sandle

Tuesday, 14 March 2017

Crosstalk between intestinal microbes and immune system

The human gut is home to some 100 trillion bacteria, comprising between 250 and 500 species. This astounding array of organisms, collectively known as the gut microbiome, is a powerful regulator of disease and health and has been implicated in conditions ranging from inflammatory bowel disease to multiple sclerosis.

Gut microbes engage in an intricately choreographed conversation with the immune system, stimulating it just enough to keep disease-causing invaders at bay, while at the same time reining it in so it doesn't mistakenly launch an attack on the body.
So far, scientists have been able to listen to bits and pieces of the conversation between bacteria and individual immune cells or a handful of genes.

Now, for the first time, scientists from Harvard Medical School have managed to "listen in" on the crosstalk between individual microbes and the entire cast of immune cells and genes expressed in the gut.

The experiments, published Feb. 16 in Cell, provide a blueprint for identifying important microbial influencers of disease and health and can help scientists develop precision-targeted treatments.

Past research has looked at links between disease and the presence or absence of certain classes of bacteria in the gut. By contrast, the HMS team homed in on one microbe at a time and its effects on nearly all immune cells and intestinal genes, an approach that offers a more precise understanding of the interplay between individual gut microbes and their hosts. Beyond that, the team said, the approach could help scientists screen for molecules or bacterial strains that can be used therapeutically to fine-tune certain immune responses.

For their experiments, the team collected 53 common bacterial species from human guts and seeded them in sterile mouse guts, one microbe at a time. Two weeks later, the scientists performed immune and genomic analyses, comparing the results with those of mice whose guts were completely microbe-free. Scientists assessed each microbe's effects on 21 types of immune cells and on the activity of the entire cast of genes that regulate intestinal immunity.

Each immune cell type was affected by bacteria in a range of ways, the team observed. Some bacteria exerted a powerful influence, while others had far more subtle effects. Very few microbes produced no effect at all.

Some bacteria boosted the activity of certain cells, while others dampened the activity of the very same cells. These oppositional effects, the researchers say, suggest an evolutionary checks-and-balances mechanism to ensure that no single bacterium can overpower the others in its effects on the immune system. Similarly, some bacteria upregulated certain genes, while others downregulated them, indicating that microbes can have balancing effects on intestinal gene expression.

A quarter of the 53 bacteria studied potently boosted the numbers of immune cells known as regulatory T cells, which are responsible for taming inflammation and maintaining immune self-tolerance to shield the body from self-inflicted immune assault. Another interesting observation, the researchers said, was that a single, little-known microbe, Fusobacterium varium, had, overall, the most powerful effect on immune cells across the board. These effects included suppression of naturally secreted antimicrobials and the ability to turn on several genes that promote inflammation.

The most potently affected class of immune cells was plasmacytoid dendritic cells, known to affect the function of regulatory T-cells and the secretion of interferons, naturally occurring proteins that fend off viruses. Thirty-eight percent of microbes boosted the levels of these dendritic cells, while 8 percent lowered their levels.


Naama Geva-Zatorsky, Esen Sefik, Lindsay Kua, Lesley Pasman, Tze Guan Tan, Adriana Ortiz-Lopez, Tsering Bakto Yanortsang, Liang Yang, Ray Jupp, Diane Mathis, Christophe Benoist, Dennis L. Kasper. Mining the Human Gut Microbiota for Immunomodulatory Organisms. Cell, 2017; DOI: 10.1016/j.cell.2017.01.022

Posted by Dr. Tim Sandle

Monday, 13 March 2017

Sleepy bacteria evolve to resist antibiotics

Antibiotic resistance is a major and growing problem worldwide. According to the World Health Organization, antibiotic resistance is rising to dangerously high levels in all parts of the world, and new resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases. But how these bacterial resistance mechanisms occur, and whether we can predict their evolution, is far from understood.

Researchers have previously shown that one way bacteria can survive antibiotics is to evolve a "timer" that keeps them dormant for the duration of antibiotic treatment. But the antibiotic kills them when they wake up, so the easy solution is to continue the antibiotic treatment for a longer duration.

Now, in new research published in the journal Science, researchers at the Hebrew University of Jerusalem report a startling alternative path to the evolution of resistance in bacteria. After evolving a dormancy mechanism, the bacterial population can then evolve resistance 20 times faster than normal. At this point, continuing to administer antibiotics won't kill the bacteria.

To investigate this evolutionary process, a group of biophysicists, led by Professor Nathalie Balaban and PhD student Irit Levin-Reisman at the Hebrew University's Racah Institute of Physics, exposed bacterial populations to a daily dose of antibiotics in controlled laboratory conditions, until resistance was established. By tracking the bacteria along the evolutionary process, they found that the lethal antibiotic dosage gave rise to bacteria that were transiently dormant, and were therefore protected from several types of antibiotics that target actively growing bacteria. Once bacteria acquired the ability to go dormant, which is termed "tolerance," they rapidly acquired mutations to resistance and were able to overcome the antibiotic treatment.

Thus, first the bacteria evolved to "sleep" for most of the antibiotic treatment, and then this "sleeping mode" not only transiently protected them from the lethal action of the drug, but also actually worked as a stepping stone for the later acquisition of resistance factors.

The results indicate that tolerance may play a crucial role in the evolution of resistance in bacterial populations under cyclic exposures to high antibiotic concentrations. The key factors are that tolerance arises rapidly, as a result of the large number of possible mutations that lead to it, and that the combined effect of resistance and tolerance promotes the establishment of a partial resistance mutation on a tolerant background.

These findings may have important implications for the development of new antibiotics, as they suggest that the way to delay the evolution of resistance is by using drugs that can also target the tolerant bacteria.

Unveiling the evolutionary dynamics of antibiotic resistance was made possible by the biophysical approach of the research team. The experiments were performed by a team of physicists, who developed a theoretical model and computer simulations that enabled a deep understanding of the reason behind the fast evolution of resistance that were observed.

Posted by Dr. Tim Sandle