MTS38 - Jonathan Eisen - An Embarrassment of Genomes

The scientific process has the power to deliver a better world and may be the most monumental human achievement. But when it is unethically performed or miscommunicated, it can cause confusion and division. Drs. Fang and Casadevall discuss what is good science, what is bad science and how to make it better.

Get the book! Thinking about Science: Good Science, Bad Science, and How to Make It Better

Dr. James Morton discusses how the gut microbiome modulates brain development and function with specific emphasis on how the gut-brain axis points to functional architecture of autism.

Watch James' talk from ASM Microbe 2023: Using AI to Glean Insights From Microbiome Data https://youtu.be/hUQls359Spo

Dr. Michael ginger, Dean of the School of Applied Sciences in the Department of Biological and geographical Science at the University of Huddersfield, in West Yorkshire, England discusses the atypical metabolism and evolutionary cell biology of parasitic and free-living protists, including Leishmania, Naegleria and  even euglinids.

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Ashley's Biggest Takeaways

• Biosensors devices that engineer living organisms or biomolocules to detect and report the presence of certain biomarkers.  
• The device consists of a bioreceptor (bacteria) and a reporter (fluorescent protein or light).
• Inda-Webb’s lab recently published a paper in Nature about using biosensors (Sub-1.4 cm3 capsule) to detect inflammatory biomarkers in the gut. The work is focused on diagnosing and treating inflammatory bowel disease, but Inda-Webb acknowledged that that is a large research umbrella.
• The next step for this research is to monitor the use of the biosensor in humans to determine what chemical concentrations are biologically relevant and to show that it is safe for humans to ingest the device.
• It is believed that the gut microbiome in humans develops in the first 1000 days to 3 years of life.
• Early dysbiosis in the gut has been linked to disease in adulthood. However, we do not have a good way to monitor (and/or influence) microbiome development.
• Inda-Webb hopes to use biosensors in diapers (wearables) to monitor microbiome development and prevent common diseases in adulthood.
• In 2015, Inda-Webb became ASM’s first Agar Art Contest winner for her piece, “Harvest System.”
• Inda-Webb is the 2023 winner of the ASM Award for Early Career Environmental Research, which recognizes an early career investigator with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings.
  • Learn More About ASM’s Awards Program

Featured Quotes:

We engineer bacteria to sense particular molecules of interest—what we call biomarkers—if they are associated with a disease. And then, we engineer a way that the bacteria will produce some kind of molecule that we can measure—what we call reporter—so that could be a fluorescent protein or light, like the one that we have in this device.

The issue is that inflammation in the gut is really very difficult to track. There are no real current technologies to do that. That is like a black box. And so, most of what we measure is what comes out from the gut, and has its limitations. It doesn't really represent the chemical environment that you have inside, especially in areas where you're inflamed. So, we really needed technologies to be able to open a window in these areas.

The final device that I am actually bringing here is a little pill that the patient would swallow and get into the gut. And then they engineer bacteria that the biosensors, will detect, let's say, nitrous oxide, which is a very transient molecule. And the bacteria are engineered to respond to that in some way—to communicate with the electronics that will wirelessly transmit to your cell phone. And from there, to the gastroenterologist.

We make the bacteria produce light. If they sense nitrous oxide, they produce light, the electronics read that, and the [information] finally gets into your phone.

Part of the challenge was that we needed to make the electronics very very tiny to be able to fit inside the capsule. And also, the amount of bacteria that we use also is only one microliter. And so, imagine one microliter of bacteria producing a tiny amount of light. Finally, the electronics need to be able to read it. So that has been also part of the challenge.

In this case, you have 4 different channels. One is a reference, and then the other 3 are the molecule of your choice. So, for example, what we show in the paper here is that we can even follow a metabolic pathway. So, you can see one more molecule turn into the other one, then into the other one. I'm really excited about that. Because normally we kind of guess as things are happening, you know, but here you can see in real time how the different molecules are changing over time. I think that's pretty exciting for microbiologist.

The immediate application would be for a follow up. Let's say the patient is going to have a flare, and so you could predict it more much earlier. Or there's a particular treatment, and you want to see what is happening [inside the gut]. But for me, as a microbiologist, one of the things I'm most excited about will be more in the longer term.

One of my favorite experiments that I do with the students is the Winogradsky column, and everyone gets super excited. So, we all have nice feelings for that. And it’s basically a column where we asked the students to bring mud from a lake, for example, and then some sources of nutrients. And then, after 6months, you will see all the layers, which is super pretty—beautiful, nice colors. But actually, that gives the concept of how the microenvironment helps to define where, or how, bacteria build communities.

And so, what I think this device is going to do is to help us identify what is this microenvironment and to characterize that. And then, from there, to know if [an individual’s] microbiome is leaning towards the disease state, or if it's already in a serious or dangerous situation, to think about treatments that can lead to a more healthy state. So, I would just say it's really to have a window into the gut, and to be able to give personalized treatment for the patient.

So, one application: I was thinking, I'm from the Boston area. So, one problem we have is getting a tick bite, right? After that, you could actually have to go through a very traumatic, antibiotic regime. I would imagine, in that case, you could [use the biosensor to] get the baseline [measurement], and then if you need to take these antibiotics, the doctors can follow how your microbiome is responding to that. Because one of the problems is that antibiotics changed the oxidation level [in the gut], and that really affects a lot the microbiome. To that point, for example, I get to know patients that they were athletes, and then, after antibiotic treatment, they have serious problems with obesity. Their life gets really messed up in many ways.

And so, what I'm thinking is, if we could monitor earlier, there are a lot of ways that we could prevent that. We could give antioxidants; we could change the antibiotic. There are things that I think the doctor could be able to do and still do the treatment that we know.
And of course, [although] we talk a lot about how much trouble antibiotics are, for certain things, we still need [them].

[The multi-diagnostic diaper] is one of my pet projects. I really love it. So yeah, basically, the issue is that the microbiome develops in the first 3 years. People even say like, 1000 days, you know. But there's really no way to monitor that. And now we're seeing that actually, if the microbiome gets affected, there are a lot of diseases that you will see in adult life. So, if we will be able to monitor the microbiome development, I really believe that we'll be able to prevent many of the diseases of tomorrow.

What happens is that babies wear diapers. So, I thought it was really a very good overlap. We call that “wearables,” you know, like devices that you can wear, and then from there, measure something connected with health.

So, in the diaper, I was excited because—different from the challenge with the ingested device, which was so tiny—here, we don't have the limitation of space. So, we could measure maybe 1000 different biomarkers and see how that builds over time.

We can measure so many things. One could be just toxic elements that could be in the environment. I try to do very grounded science, and so, my question is always, ‘what’s the actionable thing to do?’ So, I'm thinking if there was a lot of toxicity, for example, in the carpet, or in the environment where you live, those are the easiest things to change, right?

Then also, other things connecting more with the metabolism. [Often] the parents don't know that the kid has metabolic issues. So, before that starts to build and bring disease, it would be best if you could detect it as early as possible. From there, with symbiotics, we are thinking there are a lot of therapies that could engineer bacteria to produce the enzymes that the kid can’t produce.

We could also [develop] other products, like for example, a t-shirt to measure the sweat. I'm also thinking more of the milk. I'm very excited about how the milk helps to build the microbiome in the right way. And that that's a huge, very exciting area for microbiologists. And so, we could also have nursing pads that also measure [whether] the mother has the right nutrients.

My family, my grandparents were farmers, and in Argentina, really the time for harvest is very important. You can see how the city and really the whole country gets very active. And at that time [during a course Inda-Webb was taking at Cold Spring Harbor] in this course, I could see that with yeast we were having a lot of tools that would allow us to be much more productive in the field. And I thought, ‘Oh, this feels like a harvest system for yeast.’ Yes. So that was how it [Inda-Webb’s winning agar artwork, ‘Harvest System’] came out.

I really love the people. Here, [at ASM Microbe 2023], I really found that how people are bringing so much energy and really wanted to engage and understand and just connect to this idea of human flourishing, right, giving value to something, and saying, ‘okay, we can actually push the limits of what we know.’ How beautiful is that? And you know, we can learn from that. That was very exciting.

ASM Agar Art Contest

Have you ever seen art created in a petri dish using living, growing microorganisms? That's agar art! ASM's annual Agar Art Contest is a chance for you to use science to show off your creative skills.

Submissions Are Now Being Accepted!
This year's contest theme is "Microbiology in Space." Head over to our Contest Details page to get all of the information about what you need to submit your entry. Submissions will be accepted until Oct. 28!

Links for the Episode:

• Inda-Webb, et al. recent Nature publication: Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.
• Bacterial Biosensors: The Future of Analyte Detection.

Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.

Dr. Gary Procop, CEO of the American Board of pathology and professor of pathology at the Cleveland Clinic, Lerner School of Medicine discusses the importance of early detection and diagnosis in order to prevent fungal invasion leading to poor outcomes, particularly in immunocompromised patients. He emphasizes the importance of thinking fungus early, shares his passion for mentoring and talks about key updates in the recently released 7th Edition of Larone’s Medically Important Fungi.

Ashley's Biggest Takeaways

• Many invasive fungal infections are angiotrophic, meaning they actually grow toward, and into, blood vessels.
• Once the fungus has penetrated the blood vessel, the blood essentially clots, causing tissue downstream from the blood clot to die (infarction).
• When tissues that have been excised are viewed under the microscope, hyphal elements can be seen streaming toward or invading through the wall of the blood vessels. Once the clot forms, those hyphal elements can be seen in the center of the blood vessel where only blood should be.
• Antifungals cannot be delivered to areas where the blood supply has stopped. Therefore, treatment requires a combined surgical and medical approach, and the process is very invasive.
• Early detection can prevent these bad outcomes by allowing antifungal treatment to be administered before angioinvasion occurs.

Links for the Episode:

• Expand your clinical mycology knowledge with the recently released 7th edition of Larone's Medically Important Fungi: A Guide to Identification. Written by a new team of authors, Lars F. Westblade, Eileen M. Burd, Shawn R. Lockhart and Gary W. Procop, this updated edition continues the legacy of excellence established by founding author, Davise H. Larone.
  Since its first edition, this seminal text has been treasured by clinicians and medical laboratory scientists worldwide. The 7th edition carries forward the longstanding tradition of providing high-quality content to educate and support the identification of more than 150 of the most encountered fungi in clinical mycology laboratories.
  
  Get your copy today with $1 flat rate shipping within the U.S. or order the e-book! ASM members enjoy 20% off at checkout using the member promo code.

Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.

From antifungal resistance to disaster microbiology and tales of visible mold growing across the skin of patients following a tornado in Joplin, Missouri, Dr. Shawn Lockhart, Senior Clinical Laboratory Advisor in the Mycotic Diseases Branch at the CDC talks all things fungi—complete with references to pop TV shows and the recently released 7th Edition of Larone’s Medically Important Fungi.

Links mentioned:

• Larone's Medically Important Fungi: A Guide to Identification, 7th Edition (Use code: MCR20 at checkout for 20% off)
• CDC’s Mycotic Diseases Branch conducts an annual training course on the identification of pathogenic molds.

Ashley's Biggest Takeaways

• Saccharomyces means sugar-loving fungus.
• Humans have similar olfactory structures and mechanisms as insects and are similarly attracted to fermenting or rotting fruits produced by Saccharomyces.
• Research has shown that insects (and humans) prefer yeasts that produce more esters and aromatic compounds.
• Palm wine is a product that is made from sap collected from palm trees (palm sap) across the tropical band of the world.
• Fruity flavors appear to be less important to persistence of Saccharomyces strains in an Indonesian palm wine fermentation.
• This may be because palm wine fermentation is very quick, generally 1-3 days often, with a maximum of 5 days for fermentation to be conducted.
• Wineries, on the other hand, ferment annually (one fermentation per year/vintage), when the grapes are right. Grape wine fermentations can take 7 days to 2 weeks to complete.
• So different selections likely take place between the 2 fermentation products.

Featured Quotes:

When we start drawing our lens on how microbes produce food for humans, we're coopting a process that happens quite naturally. Here I'll start off talking about Saccharomyces cerevisiae, the main fermenting yeast in food and beverage production, because it's one of the most studied organisms and was the first eukaryote to be sequenced.

Saccharomyces cerevisiae, as the name implies, loves sugar, and it flourishes when there's a lot of sugar in the environment. Where is sugar found? In fruits, and that's done quite deliberately, because fruits develop sugars and flavors and aromas to attract a birds or insects or anything else that can carry their seeds elsewhere for dispersal.

Now, Saccharomyces lies dormant in the environment in a spore before it encounters a sugar-loving environment. And then it replicates very quickly and tends to dominate fermentation. Humans have coopted that into our kitchens, into our meals, into our lives, and we use that process to produce food.

As Saccharomyces starts to use this sugar, it balances up its metabolism. And as it does this, it produces aromas. These aromas have a lot of important characteristics. Humans love them, but insects also love them too.

I've been interested in the yeasts that are found naturally in sourdough starters. Sourdough is a really interesting system. Because you've got yeast and bacteria interacting with one another.

One of the things we are collaborating on with colleagues in France at Inrae, Dr. Delphine Sicard, is to understand some of the non-Saccharomyces yeasts that are naturally occurring in sourdough starters. So here we're looking at a collection of a yeast called Kazachstania humilis and trying to understand how it has adapted to the sourdough environment, how its sustained over time and how different global populations differ to one another.

And this, of course, is of interest to the baking industry because not only do artisanal bakers have sort of an undiscovered wealth of biodiversity in their starters, baking companies also have an interest in using different sorts of flavors and bread for the commercial markets.

The connection between a chemical profile and a person’s sensory preference isn't something that's complete and direct. So, in every method that we use, there's always caveats, but we try to correlate it. Let's start off with the chemical characterization. We use headspace sampling, analytical chemistry, separation with gas chromatography and identification with mass spectrometry.

And we use different 2-dimensional methods to be able to understand what the very small compounds are, and to be able to identify them. We can semi-quantify these to be able to make comparisons between different fermentations.

We know from wine fermentations and understanding preferences of wine that, in some cases, a particular increase, or an abundance of a particular compound, can be extremely attractive. And that might depend on the style of wine.

What we've discovered through this process is that different people prefer different flavors. Makes sense, doesn't it? We like different things. But some really interesting results from our lab, show that people from different cultural backgrounds have different preferences. And here we're using here in Melbourne, I'm very lucky to work with some very talented postdocs and Ph.D. students from China, who have very different preferences for wine than an Australian does. Of course, Australians are quite heterogeneous in their in their cultural diversity as well. But there's certain flavors that our Chinese colleagues tend to prefer. So we decided to investigate this a little bit more.

So for this study, we recruited wine experts from Australia, actively working in the wine industry, and also wine experts from China, working in the wine industry, and brought them to campus and ask them to rate their preferences on particular aromas and flavor characteristics that they noted in a panel of wines. These were very high-quality wines. We knew with wine experts, we couldn't just give them our loved wines, for example, which can be a little bit patchy quality wise. We asked them to rate their preferences, and then we collected saliva samples.

The saliva samples were really interesting. We looked at 2 different aspects. We looked at the proteins that were present in the saliva samples. And we also looked at the oral microbiome. So the salivary microbiome—the bacteria, in particular—that are present. We found some really interesting things. And this has sparked a big area in our lab.

So while the main enzymatic activities in the different groups of participants were quite similar—so esterase activity, Alpha amylase activity were similar—we found that there was a difference in the abundance of proline rich proteins and other potential flavor carrying compounds. Now, this is quite speculative. We'd like to know why this is the case. And so we're delving a little bit further into this area.

What we do know though is that the abundances, especially if these proline rich proteins, is correlated with how people perceive the stringency. Now stringency is one of those characteristics in wine which is quite difficult to appreciate. It’s a lack of drying characteristic on the tongue and in the mouth and oral cavity. Some people find it quite attractive, others don't.

But we found that the abundance of these polyproline-rich proteins correlates with stringency. This is, in fact, found in other studies because proline-rich proteins interact with polyphenols in the wine, and precipitate, which changes the sensation of astringency in the oral cavity. So here we've got a nice link to protein abundance and how people perceive flavor. But we're talking about microbiology, so maybe I should delve into the microbiological aspects of these studies as well.

In that particular study that I'm referring to, we used wines that were naturally fermented, and that's the other variability that we need to consider when we think about wines from different areas. So, a natural fermentation, in a wine sense, is the grapes are harvested, and whatever microflora is present on the grapes will just ferment, and we often don't know what the main fermenting parties are. But if you contrast that with a majority of commercial wine that's produced, mainly in Australia, but also worldwide, it's inoculated with a selected strain of Saccharomyces or maybe 2 selected strains of Saccharomyces, and that tends to produce a fairly similar flavor profile, regardless of region.

So, you can flatten out geographical characteristics and indications of flavor by inoculating a particular strain of yeast to ferment. That's not true with a natural fermentation, because that's conducted by the yeasts, and also the bacteria which just happened to be in the environment. So, I agree with you there is a lot of regional variation with wine flavor. And we can correlate that with regional diversity of yeast, but only if the wines are naturally fermented not if they're inoculated with a selected strain.
 

Links for the Episode:

• LC-ESI-QTOF/MS Characterisation of Phenolic Acids and Flavonoids in Polyphenol-Rich Fruits and Vegetables and Their Potential Antioxidant Activities.
• Frozen, canned or fermented: when you can't shop often for fresh vegetables, what are the best alternatives?
• Early Prediction of Shiraz Wine Quality Based on Small Volatile Compounds in Grapes.
• Building the climate resilience of Melbourne's Food System.

Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.

Dr. Steve Diggle, ASM Distinguished Lecturer and Microbiology Professor at the Georgia Institute of Technology in Atlanta, Georgia and Dr. Freya Harrison, Associate Microbiology Professor at the University of Warwick in Coventry, U.K., discuss the science behind medieval medical treatments and the benefits of interdisciplinary research.

Ashley's Biggest Takeaways

• Diggle and Harrison met in Oxford, where Harrison was finishing up her Ph.D. and Diggle was doing background research for his work studying evolutionary questions about quorum sensing.
• When Diggle began searching for a postdoc, Harrison, who had been conducting an independent fellowship at Oxford and studying social evolution, applied.
• The AncientBiotics Consortium is a group of experts from the sciences, arts and humanities, who are digging through medieval medical books in hopes of finding ancient solutions to today’s growing threat of antibiotic resistance.
• The group’s first undertaking was recreation and investigation of the antimicrobial properties of an ancient eyesalve described in Bald’s Leechbook, one of the earliest known medical textbooks, which contains recipes for medications, salves and treatments.
• The consortium found that the eyesalve was capable of killing MRSA, a discovery that generated a lot of media attention and sparked expanded research efforts.  
• The group brought data scientists and mathematicians into the consortium (work driven by Dr. Erin Connelly from the University of Warwick).
• Together, the researchers began scouring early modern and medieval texts and turning them into databases.
• The goal? To mathematically data mine these recipes see which ingredients were very often or non-randomly combined in ancient medical remedies.
• The group recently published work showing synergistic antimicrobial effects of acetic acid and honey.
• They are also working to pull out the active compounds from Bald’s eyesalve and make a synthetic cocktail that could be added to a wound dressings.

• A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity.
• Medieval medicine: the return to maggots and leeches to treat ailments.
• A case study of the Ancientbiotics collaboration.
• Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers.
• Sweet and sour synergy: exploring the antibacterial and antibiofilm activity of acetic acid and vinegar combined with medical-grade honeys.

Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.

Ashley's Biggest Takeaways

• Lee applied for her job at NASA in 2020.
• Prior to her current position, she completed 2 postdocs and spent time researching how microbes respond to stress at a population level and understanding diversity in microbial populations.
• She has a background in microbial ecology, evolution and bioinformatics.
• Model organisms are favored for space research because they reduce risk, maximize the science return and organisms that are well understood are more easily funded.
• Unsurprisingly, most space research does not actually take place in space, because it is difficult to experiment in space.
• Which means space conditions must be replicated on Earth.
• This may be accomplished using creative experimental designs in the wet-lab, as well as using computational modeling.

Links for the Episode:

• Out of This World: Microbes in Space.
• Register for ASM Microbe 2023.
• Add “The Math of Microbes: Computational and Mathematical Modeling of Microbial Systems,” to your ASM Microbe agenda.

Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.