Treatment with antibiotics frees sugars used by pathogens

We have tiny visitors that have taken advantage of their evolutionary squatting rights throughout our bodies; these microbes make up our microbiome. Nobel Laureate Joshua Lederberg best defined the human microbiome as “the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space”.

We are Soylent Microbiome, Soylent Microbiome is US!

This means we have 3 distinct types of microorganisms sharing our bodies with us:

1) The Commensals: Commensalism is relationship between two organisms where one benefits without affecting the other, derived from the English work commensal meaning “eating at the same table”.

2) The Symbionts: This is a clear mutualistic relationship, both parties are benefiting, both parties are happiest. We provide love to our microbiome, they provide love back to us (and by love I mean nutrients and protection from harm).

3) The Pathogens: These are the microbes that cause disease. The main distinguishing factor of a pathogen vs. a commensal is that a pathogen causes harm to the host.

Maintaining the perfect balance of all 3 of these microbe-types is essential for the equilibrium of the microbiome. An altered microbiome has been linked to depression, obesity, diabetes, anxiety, autism, cancer, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, fibromyalgia and many other negative aspects of being human that we have yet to link.

We know one sure-fire way to disrupt the gut microbiome is to treat a human with oral antibiotics. Yes, the cure for most bacterial infection is to wipe out your entire ecological masterpiece you’ve worked on for decades in your gut.

Essentially, your commensals and symbionts work together to protect you from the potential harm that can be caused by the pathogens. We don’t understand fully how the protection works, but we do know that the presence of commensals and symbionts are essential for keeping the pathogens at bay.

One hypothesis is that your commensals and symbionts are creating a literal barrier between you and the pathogens, and if you wipe out this barrier with antibiotics that is when the scary pathogens take over.

In fact, oral antibiotic use is one of the leading risk factors for the disease associated with Salmonella ssp. and Clostridium difficile (C diff).

In most cases, Salmonella spp. causes salmonellosis (or food poisoning) and typhoid fever, whereas C. difficile causes antibiotic-associated diarrhea (AAD). In more severe cases Salmonella spp. can cause sepsis and C. difficile can cause “pseudomembranous colitis”, a severe inflammation of the colon.

But back to our story! The key is to keep these pathogens quiet and happy, and if oral treatment with antibiotics disrupts the microbiome barrier that leads to these pathogens causing disease and harm…

WHAT IS IT ABOUT THE DISRUPTION OF THE MICROBIOME BY ANTIBIOTICS THAT BENEFITS THE PROLIFERATION OF THE PATHOGENS?

Turns out, sugar availability is at an all-time high for these pathogens when the microbiome is disturbed, specifically an increase in sialic acid (yum!) and fucose (yummier!).

The mammalian host is nutrient diverse and rich, allowing for microbial populations to snuggle up and settle in – however the intestinal microbial community (or the microbiota) is composed of trillions of bacterial cells, making nutrient availability a little more stringent for those invaders that try to squat in the gut.

Alteration of the microbiome leads to an alteration of the carbohydrate availability in your gut – and the pathogens that are now rattled by the disruption of the microbiome now have unlimited food.

More sugar = more replication = more disease

Think of Salmonella spp. and C. difficile as Scrooge McDuck rolling around in his pile of money.

Katherine Ng in Justin Sonnenburg’s lab at Stanford University found that during oral treatment of antibiotics there is a spike in microbiota-liberated sugars that can then be taken up and eaten by our protagonists, Salmonella spp. and C. difficile to increase their replication and disease in the gut.

Specifically, Salmonella spp. are utilizing the liberated sialic acids and fucose from disturbed commensals in the gut after antibiotic treatment, and C. difficile is utilizing the the sialic acids liberated by the same commensals.

Interestingly, when you delete these catabolic pathways (metabolic pathways in the bacteria that are used to break down molecules into smaller units for energy) in Salmonella spp. where it can no longer use sialic acid and fucose as carbon sources, it can no longer replicate and cause disease to the same levels in antibiotic-treated mice.

Not only that! When you have a mouse with a microbiome that cannot produce sialic acid, therefore it reduces free sialic acid levels, C. difficile no longer causes disease to the same levels after treatment with antibiotics. No free sugars? No good for our protagonists!

What if we took these mice that had a microbiome that does not produce sialic acid and we fed them sialic acid in their diet (nom nom), then we treated the mice with antibiotics = C. difficile reigns again!

It looks like that usually, when the microbiome is happy, it’s eating all the free sialic acid and fucose and not saving any for the pathogens, which keeps the pathogens at a minimum and less of a nuisance – however, upon antibiotic treatment the microbiome is disturbed, which breaks down the wall of commensal/symbionts blocking pathogens from using these sugars… therefore the pathogens are eating good, replicating, and eventually cause disease.

Pathogens, always the opportunists.

HOW CAN WE USE THIS INFORMATION FOR GOOD?

CAN WE USE THIS INSIGHT FOR NEW THERAPEUTIC APPROACHES TO PREVENTING DISEASES CAUSED BY ANTIBIOTIC-ASSOCIATED PATHOGENS?

During treatment with oral antibiotics what if modulated diet to decrease sialic acid and fucose? Decreasing the availability for pathogens in the gut?

What if we could give a probiotic that was deficient in sialic acid and fucose production, therefore it would be established in the gut and if/when antibiotic are used and disturb the microbiome there would be minimal free sialic acid and fucose because there was none to begin with?

What if we designed an inhibitor that blocked sialic acid and fucose catabolism pathways in the pathogens? Therefore, when antibiotics are used and disrupt the microbiome allowing for pathogens like Salmonella spp. and C. difficile to replicate – we treat with this inhibitor of sialic acid/fucose catabolism, essentially the pathogens could then pick up the sialic acid and fucose from the environment but they couldn’t use is for energy. No energy = no replication = no disease.

Those are just a few of my ideas. What about you?

Image-focused: This week in astronomy

Astronomers collect light. That’s all they do. They make it into pictures and scatter plots (and histograms and spectra and tables), but everything they figure out comes from photons with different energies, wavelengths, orientations, origins, and hair colors. In celebration of that fact, it’s Friday Picture Day. The four images below were released this week and show what astronomers are, at this moment, hunched over computers studying.

1. COMET ISON

Credit: NASA, ESA, and the Hubble Heritage Team (STScI/AURA)

Where are you going so fast, space object? You look like a ghost or Kirby.

But you are not. You are a loosely packed ball of dust and ice screaming through space. You are Comet ISON, and the Hubble Space Telescope took this picture of you when you were 363 million miles from the Sun and 402 million miles from Earth.

Oh, you weren’t ready to have your picture taken? You’re not looking your best yet? I’m sorry. I’m sorry I’m not sorry. Hurry up and get closer to the Sun, and we’ll reshoot when the Sun is blowing your gas and dust into tails hundreds of millions of miles long. You’re kind of cute now, but by November, you’ll look like you’ve been doping.

Credit: NASA/JPL-Caltech/Space Science Institute

2. EARTH FROM SATURN

That pale blue dot with the not-a-real-thing arrow pointing at it? That’s Earth — from 898 million miles away. The Cassini spacecraft, which is currently researching the hell out of Saturn, took images showing 33 different areas of the ring system. One view happened to include our planet. “Happened to include” — yeah, right. Stop creepin’, Cassini.

3. GALAXY NEIGHBORS

Voila, it’s the Whirlpool Galaxy … and that hanger-on, the galaxy that feels as small as it looks because it is constantly referred to as “the companion galaxy.” It’s called NGC 5195, you guys. Call it by its name. Treat it the way you would want to be treated.

The WIYN telescope at the National Optical Astronomy Observatory’s Kitt Peak facility took this picture in one go because it has a fancy new wide field-of-view camera. That’s “something that even the Hubble Space Telescope cannot do,” the press release said. Not to brag, bro.

4. THE SUN ACTING LIKE THE SERIOUSLY WEIRD THING IT IS

The Sun’s outer atmosphere — the corona — is millions of degrees hotter than its surface — the photosphere. Which doesn’t seem to make sense because heat can’t flow from a colder thing to a hotter thing, but the corona must be getting heat somehow. Astronomers want to learn more about the transition area between the photosphere and the corona.

The Interface Region Imaging Spectrograph (IRIS), which opened its little mechanical eyeballs for the first time July 17, took this image of two sunspot regions (dark patches in the upper left and lower right). The observatory sees three different bands of ultraviolet light and snaps an image every 10 seconds. Through this high-speed, intensive project, scientists are hoping to figure out what the F is going on over there.

Antibiotics damage human cells

I wanted to think of a very clever title for this epic topic, but I wanted to cut straight to the point. As the antibiotic era is coming to an end due to the emergence of antibiotic-resistant pathogens, it is alarming that we had not sufficiently explored the deleterious side effects that these drugs cause on our own cells.

James Collins and his group from the Howard Hughes Medical Institute published last week in Science Translational Medicine (my new favorite journal) a remarkable study that shows antibiotics not only harm bacterial cells, but mammalian cells too.

Let’s start in the 40’s…

Looking back in time, the term “antibiotics” was first used in 1942 by Selman Waksman to describe any substance synthesized by a microorganism that negatively affects the growth of other microorganisms. Antibiotics inhibit growth of microorganisms through a variety of mechanisms ranging from molecules that bind to ribosomal subunits to inhibit protein synthesis to disruption of bacterial lipid membranes.

Generally all of the antibiotics can be categorized into two groups: 1) bactericidal antibiotics and 2) bacteriostatic antibiotics.

Bactericidal antibiotics directly kill bacteria (ie; penicillin, which blocks synthesis of the bacterial cell wall), whereas bacteriostatic antibiotics slow their growth or reproduction (ie; a macrolide like azithromycin, which binds to the 50S subunit

Interestingly, in 2007 James Collins and his group released a set of data that suggests that all bactericidal antibiotics have a common mechanism of killing bacteria. This blew our original knowledge of bactericidal antibiotics out the water. Here we’ve been thinking for nearly 7 decades that each individual class of bactericidal antibiotics kill through different mechanisms, but we were wrong? Perhaps (this hypothesis is highly debated, but should not be discounted!).

This study suggests that all bactericidal antibiotic killing starts out as an array of diverse disruption mechanisms to throw the bacteria out of homeostatis, but all of these mechanisms have a similar end point – production of “highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria, which ultimately contribute to cell death”.

Hydroxyl radicals are highly reactive ions that can damage virtually any type of molecule including DNA, lipids, amino acids… that’s just a taste of what these assassins can target and all three of those things have something in common… they are required for LIFE.

Not just bacterial life, ALL LIFE.

Ah ha!

So if production of hydroxyl radicals can have such a harmful affect on the essential essence of bacteria (DNA, proteins, amino acids, lipids, etc), couldn’t the production of hydroxyl radicals have an affect on these same essentials in mammalian cells?

Precisely!

Interestingly prolonged use of antibiotics is associated with various side effects ranging from ototoxicity (damage to the ear due to use of antibiotics like aminoglycosides, which are antibiotics that are bactericidal in high concentrations) to nephrotoxicity (kidney disfunction). Despite these correlations, no real studies have been conducted on the adverse affects of bactericidal antibiotics on mammalian cells!

Turns out James Collins and his group show, after intense investigation into this matter, that bactericidal antibiotics (specifically quinolones, aminoglycosides, and beta-lactams) can cause mitochondrial dysfunction and reactive oxygen species (ROS) overproduction in human and mice cells.

Turns out hydroxyl radicals are a type of ROS. Whoa mama. Ultimately the over-production of ROS induced damage to DNA, proteins, and membrane lipids leading to tissue damage in the host.

Figure: These are sections of mouse mammary gland tissue after treatment with bactericidal antibiotics (ciprofloxacin, ampicillin, and kanamycin), with and without the anti-oxidant N-acetyl-L-cysteine (NAC), or a bacteriostatic antibiotic (tetracycline). The protein damage in the mammary gland tissue is shown by the red arrows pointing to the red dots (anti-nitrotyrosine antibody that measures oxidative protein damage), black arrows point to protein damage to connective tissues.

Amazing, but somewhat intuitive, if they gave mice the Food and Drug Administration (FDA)-approved antioxidant (think pomegranates, or don’t apparently that’s not scientifically proven), N-acetyl-L-cysteine (NAC), it completely alleviated all of the scary side affects of these bactericidal antibiotics.

There is huge implication for this study on long-term antibiotic treatment or treatment of antibiotic cocktails in the ICU (mostly immune suppressed patients) in which antibiotic regiments may have to be revised – perhaps by supplementing patients afternoon sandwiches with some anti-oxidant containing blueberries?

Sassy supernovae: A new 3D simulation shows dying stars slosh

These are simulated stars, not what you’re thinking. I know what you’re thinking *(see last graphic).

It’s no secret that when a massive star dies, it often does so dramatically–in a huge explosion known as a supernova. Supernovae outshine entire galaxies and enrich the universe with the heavy elements that are necessary to make those gold chains you wear.

It is kind of a secret, though, that scientists don’t really know how supernovae happen. When they try to recreate these blasts using simulations, the physical laws plus the physical material don’t lead to the explosions we see IRL.

Scientists have solid ideas about stars’ interiors at the ends of their lives. And good ideas about the reasons stars might choose to ex- instead of implode. But when they put the details of those good ideas together, a) that’s a lot of details, b) the combo does not a supernova make.

Some supernovae leave behind neutron stars, objects about 1.4 times the mass of the Sun that are crunched down to the diameter of an earthly city and spin up to 716 times per second. They’re like gigantic atomic nuclei, if gigantic atomic nuclei were also possessed carousels.

So when a massive star dies, the stellar core is collapses inward and the supernova expels material out into space. Current simulations get stuck around the point where the implosion becomes an explosion. But these simulations often are two-dimensional and involve vastly simplified parameters. After all, there are only so many supercomputers (and also only so many people who want to write code that robust).

The theory out in front right now says that neutrinos — high-energy, low-mass particles — result from the collapse and, in their excitement to leave the star’s deathbed, collide mightily with the star’s outer layers. The layers absorb the neutrinos’ mighty energy, causing a shock wave that results in the actual supernova.

With 150 million processor hours, 16,000 cores working in parallel, and 4.5 months of continuous computing, a research team headed in Garching was able to simulate — for the first time — a detail-oriented 3D supernova explosion. This simulation produced “many Terabytes” of data, so after those 4.5 months of chugging were over, the work was far from done.

After analysis, they found evidence that neutrinos were heating their simulated gas: it was bubbling and producing fat-headed plumes, which convection, fueled by temperature increase, would cause in a fluid. They also saw sloshing, which other scientists have seen and dubbed “Standing Accretion Shock Instability” (SASI). In some other simulations, SASI had just led to more SASI, leaving the researchers with comically sloppy stars that wiggled but never exploded.

*These are not alien fetusus hidden for years by the government (Hanke, et al.).

SASI had not been observed at all in an ultra-complex simulation like this one, but it’s important because it explains asymmetric supernova. If a star is just sitting there one moment and then explodes the next, the material should all go out at the same speed at the same time. But if the star is being SASI (get it? sassy?), the internal velocities and distributions of its plasma are not homogeneous, so the explosion won’t be, either.

And from a “process of science” standpoint, I think it’s cool that the team can find experimental evidence to support the results of their 0101010110 supernovae. The neutrinos that we receive on Earth and the gravitational waves that the star’s sloshings impress upon spacetime are both detectable (or at least theoretically so).

So what are the team members going to do now that they’ve modeled a supernova?

Go to Disney World?

No: According to the press release, they “plan to perform more and longer simulations.”

What’s Closer Than Moon

Unlocking the Secrets of Asteroid YU55: A Deep Dive with the Green Bank Telescope

In an ambitious endeavour to peel back the layers of cosmic mysteries, Dr. Michael Busch and his team have turned their sights toward asteroid YU55, utilizing the formidable Green Bank Telescope (GBT) to explore what lies beneath its surface. This initiative aims to measure the temperature of the material beneath the asteroid’s crust and quantify the energy required to alter this temperature. This research marks a significant leap in our understanding of asteroids, potentially unveiling new insights into the formation and evolution of our solar system.

Asteroid YU55, a near-Earth object discovered in 2005, has intrigued scientists with its relatively close approaches to Earth and size, measuring approximately 360 meters in diameter. Its proximity and dimensions make it an ideal candidate for detailed study, offering a window into these celestial wanderers’ composition and thermal properties.

The Green Bank Telescope, nestled in the National Radio Quiet Zone in West Virginia, USA, is the world’s largest fully steerable radio telescope. Its sensitivity and precision make it an invaluable tool for probing the mysteries of the universe, from distant galaxies to nearby asteroids like YU55. By analyzing the radio waves emitted and reflected by the asteroid, Dr. Busch and his team can infer the temperature below its surface and the specific heat capacity of its material—essentially, how much energy is required to change the temperature of this material.

Understanding the thermal properties of YU55 opens up new avenues of inquiry into the broader questions of asteroid composition and behaviour. For instance, knowing how heat is absorbed and retained by an asteroid can offer clues about its structure, including whether it’s a solid rock or a “rubble pile” composed of many more minor rocks held together by gravity. This information is crucial for assessing the threat of near-Earth objects and developing potential strategies for asteroid deflection or resource utilization.

Furthermore, the study of YU55’s thermal properties can shed light on the conditions of the early solar system. Asteroids are considered to be remnants of the primordial material that formed the planets. By understanding their composition and thermal characteristics, scientists can piece together the history of solar system formation and the processes that led to the creation of Earth and its neighbours.

Dr. Busch’s work with the Green Bank Telescope represents a critical step in exploring the solar system’s smaller bodies. By expanding our knowledge of asteroids like YU55, we enhance our ability to protect Earth from potential impacts and deepen our understanding of the cosmos and our place within it. This research underscores the importance of continued investment in space science and the technologies that enable it, as each discovery brings us closer to answering the fundamental questions of our existence.

Well I’m Back To Regular Life

From Fields to Cityscapes: A Scientist’s Journey

Welcome to my blog! Today, I want to share the extraordinary journey of a scientist whose world is rooted deeply in the serene setting of a farm, amidst the whispers of plants and the secrets of nature. Let’s go on this intriguing voyage from a rural wonderland to the bustling heart of Toronto and back again.

A Scientist in Her Natural Habitat

Our story begins on a sprawling farm, tucked away in the countryside. Here, Dr. Emily Forrest, a dedicated botanist, spends her days enveloped in the world of plants. Her farm is not just a place of residence but a living laboratory where nature is both the subject and teacher. Her experiments range from understanding plant genetics to exploring sustainable farming techniques. Amidst rows of greenery, Emily’s world is peaceful, predictable, and profoundly satisfying.

The Call of Toronto

One sunny morning, Emily receives an invitation to present her groundbreaking research at a major science conference in Toronto. The prospect of stepping into such a vast, unknown urban world is both thrilling and daunting. As she packs her bags, there’s a sense of excitement mingled with a touch of apprehension.

City Wonders

Toronto, with its towering skyscrapers and streams of people, is a stark contrast to her tranquil farm. Emily is amazed by the city’s vibrant energy – the bustling streets, diverse neighborhoods, and the pulsating rhythm of city life. She explores the iconic CN Tower, strolls through the bustling St. Lawrence Market, and experiences the cultural mosaic at Kensington Market. The city, a stark contrast to her life among the plants, offers a feast for the senses and an array of new experiences.

Illuminating Minds

At the conference, Emily presents her research to an audience of esteemed peers. The response is overwhelmingly positive, opening doors to new collaborations and perspectives. She realizes that her work on the farm has broader implications than she ever imagined, influencing urban agriculture and sustainability in big cities like Toronto.

Homeward Bound

As her time in Toronto comes to a close, Emily feels a mix of reluctance and eagerness to return home. The city, with all its excitement and discoveries, was exhilarating, but the farm is where her heart truly lies. Upon returning, she finds comfort in the familiar rustle of leaves and the earthy scent of soil. Her experiences in Toronto have not only broadened her horizons but also deepened her appreciation for her peaceful life among the plants.

Emily’s journey from the farm to the city and back is a vivid reminder of the beauty and diversity of our world. It teaches us that while we may venture far and wide, exploring and learning, there’s always a unique charm in the simplicity and peace of our roots. Emily continues her experiments with a renewed spirit, understanding that every environment, whether a bustling city or a quiet farm, has its own lessons to teach us.

Epilogue

I hope this story inspires you to embrace the adventures life offers while cherishing the tranquility of your own ‘farm’, wherever that may be. Stay tuned for more stories and reflections from the fascinating world around us.