Tag Archives: Bioengineering

Microbiology

Swiss researchers identify plastic-degrading microbial strains in the Alps and Arctic region

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May 13 2023Reviewed by Lily Ramsey, LLM

Finding, cultivating, and bioengineering organisms that can digest plastic not only aids in the removal of pollution, but is now also big business. Several microorganisms that can do this have already been found, but when their enzymes that make this possible are applied at an industrial scale, they typically only work at temperatures above 30 °C. The heating required means that industrial applications remain costly to date, and aren’t carbon-neutral. But there is a possible solution to this problem: finding specialist cold-adapted microbes whose enzymes work at lower temperatures.

Scientists from the Swiss Federal Institute WSL knew where to look for such micro-organisms: at high altitudes in the Alps of their country, or in the polar regions. Their findings are published in Frontiers in Microbiology.

“Here we show that novel microbial taxa obtained from the ‘plastisphere’ of alpine and arctic soils were able to break down biodegradable plastics at 15 °C,” said first author Dr Joel Rüthi, currently a guest scientist at WSL. “These organisms could help to reduce the costs and environmental burden of an enzymatic recycling process for plastic.”

Rüthi and colleagues sampled 19 strains of bacteria and 15 of fungi growing on free-lying or intentionally buried plastic (kept in the ground for one year) in Greenland, Svalbard, and Switzerland. Most of the plastic litter from Svalbard had been collected during the Swiss Arctic Project 2018, where students did fieldwork to witness the effects of climate change at first hand. The soil from Switzerland had been collected on the summit of the Muot da Barba Peider (2,979 m) and in the valley Val Lavirun, both in the canton Graubünden.

The scientists let the isolated microbes grow as single-strain cultures in the laboratory in darkness and at 15 °C and used molecular techniques to identify them. The results showed that the bacterial strains belonged to 13 genera in the phyla Actinobacteria and Proteobacteria, and the fungi to 10 genera in the phyla Ascomycota and Mucoromycota.

Surprising results

They then used a suite of assays to screen each strain for its ability to digest sterile samples of non-biodegradable polyethylene (PE) and the biodegradable polyester-polyurethane (PUR) as well as two commercially available biodegradable mixtures of polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA).

None of the strains were able to digest PE, even after 126 days of incubation on these plastics. But 19 (56%) of strains, including 11 fungi and eight bacteria, were able to digest PUR at 15 °C, while 14 fungi and three bacteria were able to digest the plastic mixtures of PBAT and PLA. Nuclear Magnetic Resonance (NMR) and a fluorescence-based assay confirmed that these strains were able to chop up the PBAT and PLA polymers into smaller molecules.

“It was very surprising to us that we found that a large fraction of the tested strains was able to degrade at least one of the tested plastics,” said Rüthi.

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The best performers were two uncharacterized fungal species in the genera Neodevriesia and Lachnellula: these were able to digest all of the tested plastics except PE. The results also showed that the ability to digest plastic depended on the culture medium for most strains, with each strain reacting differently to each of four media tested.

Side-effect of ability to digest plant polymers

How did the ability to digest plastic evolve? Since plastics have only been around since the 1950s, the ability to degrade plastic almost certainly wasn’t a trait originally targeted by natural selection.

Microbes have been shown to produce a wide variety of polymer-degrading enzymes involved in the break-down of plant cell walls. In particular, plant-pathogenic fungi are often reported to biodegrade polyesters, because of their ability to produce cutinases which target plastic polymers due their resemblance to the plant polymer cutin.”

Dr Beat Frey, Last Author, Senior Scientist and Group Leader, WSL

Challenges remain

Since Rüthi et al. only tested for digestion at 15 °C, they don’t yet know the optimum temperature at which the enzymes of the successful strains work.

“But we know that most of the tested strains can grow well between 4 °C and 20 °C with an optimum at around 15 °C,” said Frey.

“The next big challenge will be to identify the plastic-degrading enzymes produced by the microbial strains and to optimize the process to obtain large amounts of proteins. In addition, further modification of the enzymes might be needed to optimize properties such as protein stability”.

Source:

Frontiers

Journal reference:

de Freitas, A. S. et al. (2023). Amazonian dark earths enhance the establishment of tree species in forest ecological restoration. Frontiers in Soil Science. doi.org/10.3389/fsoil.2023.1161627.

Microbiology

Bioengineered drug candidate can counter S. aureus infection in early tests

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Reviewed by Emily Henderson, B.Sc.Apr 24 2023

Researchers at NYU Grossman School of Medicine and Janssen Biotech, Inc. have shown in early tests that a bioengineered drug candidate can counter infection with Staphylococcus aureus – a bacterial species widely resistant to antibiotics and a major cause of death in hospitalized patients.

Experiments demonstrated that SM1B74, an antibacterial biologic agent, was superior to a standard antibiotic drug at treating mice infected with S. aureus, including its treatment-resistant form known as MRSA.

Published online April 24 in Cell Host & Microbe, the new paper describes the early testing of mAbtyrins, a combination molecule based on an engineered version of a human monoclonal antibody (mAb), a protein that clings to and marks S. aureus for uptake and destruction by immune cells. Attached to the mAb are centyrins, small proteins that prevent these bacteria from boring holes into the human immune cells in which they hide. As the invaders multiply, these cells die and burst, eliminating their threat to the bacteria.

Together, the experimental treatment targets ten disease-causing mechanisms employed by S. aureus, but without killing it, say the study authors. This approach promises to address antibiotic resistance, say the researchers, where antibiotics kill vulnerable strains first, only to make more space for others that happen to be less vulnerable until the drugs no longer work.

To our knowledge, this is the first report showing that mAbtyrins can drastically reduce the populations of this pathogen in cell studies, and in live mice infected with drug-resistant strains so common in hospitals. Our goal was to design a biologic that works against S. aureus inside and outside of cells, while also taking away the weapons it uses to evade the immune system.”

Victor Torres, PhD, Lead Study Author, the C.V. Starr Professor of Microbiology and director of the NYU Langone Health Antimicrobial-Resistant Pathogen Program

One-third of the human population are carriers of S. aureus without symptoms, but those with weakened immune systems may develop life-threatening lung, heart, bone, or bloodstream infections, especially among hospitalized patients.

Inside out

The new study is the culmination of a five-year research partnership between scientists at NYU Grossman School of Medicine and Janssen to address the unique nature of S. aureus.

The NYU Langone team together with Janssen researchers, published in 2019 a study that found that centyrins interfere with the action of potent toxins used by S. aureus to bore into immune cells. They used a molecular biology technique to make changes in a single parental centyrin, instantly creating a trillion slightly different versions of it via automation. Out of this “library,” careful screening revealed a small set of centyrins that cling more tightly to the toxins blocking their function.

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Building on this work, the team fused the centyrins to a mAb originally taken from a patient recovering from S. aureus infection. Already primed by its encounter with the bacteria, the mAb could label the bacterial cells such that they are pulled into bacteria-destroying pockets inside of roving immune cells called phagocytes. That is unless the same toxins that enable S. aureus to drill into immune cells from the outside let it drill out of the pockets to invade from the inside.

In a “marvel of bioengineering,” part of the team’s mAbtyrin serves as the passport recognized by immune cells, which then engulf the entire, attached mAbtyrin, along with its centyrins, and fold it into the pockets along with bacteria. Once inside, the centyrins block the bacterial toxins there. This, say the authors, sets their effort apart from antibody combinations that target the toxins only outside of cells.

The team made several additional changes to their mAbtyrin that defeat S. aureus by, for instance, activating chain reactions that amplify the immune response, as well by preventing certain bacterial enzymes from cutting up antibodies and others from gumming up their action.

In terms of experiments, the researchers tracked the growth of S. aureus strains commonly occurring in US communities in the presence of primary human immune cells (phagocytes). Bacterial populations grew almost normally in the presence of the parental antibody, slightly less well in the presence of the team’s engineered mAb, and half as fast when the mAbtyrin was used.

In another test, 98% of mice treated with a control mAb (no centyrins) developed bacteria-filled sores on their kidneys when infected with a deadly strain of S. aureus, while only 38% of mice did so when treated with the mAbtyrin. Further, when these tissues were removed and colonies of bacteria in them counted, the mice treated with the mAbtyrin had one hundred times (two logs) fewer bacterial cells than those treated with a control mAb.

Finally, the combination of small doses of the antibiotic vancomycin with the mAbtyrin in mice significantly improved the efficacy of the mAbtyrin, resulting in maximum reduction of bacterial loads in the kidneys and greater than 70% protection from kidney lesions.

“It is incredibly important,” said Torres, “that we find new ways to boost the action of vancomycin, a last line of defense against MRSA.”

Along with Torres, authors from the Department of Microbiology at NYU Langone were Rita Chan, Ashley DuMont, Keenan Lacey, Aidan O’Malley, and Anna O’keeffe. The study authors included 13 scientists from Janssen Research & Development (for details see the study manuscript).

This work was supported by Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, under the auspices of an exclusive license and research collaboration agreement with NYU. Torres has recently received royalties and consulting compensation from Janssen and related entities. These interests are being managed in accordance with NYU Langone policies and procedures.

Source:

NYU Langone Health / NYU Grossman School of Medicine

Journal reference:

Buckley, P. T., et al. (2023). Multivalent human antibody-centyrin fusion protein to prevent and treat Staphylococcus aureus infections. Cell Host & Microbe. doi.org/10.1016/j.chom.2023.04.004.

Microbiology

Gut-on-a-chip devices can bridge lab models and human biology

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Reviewed by Emily Henderson, B.Sc.Feb 28 2023

The gut is one of the most complex organs in the body. Inside, it teems with a diverse microbial population that interacts and cooperates with intestinal cells to digest food and drugs. Disruptions in this microbiome have strong links to a wide spectrum of diseases, such as inflammatory bowel disease, obesity, asthma, and even psychological and behavioral disorders.

Valid models of the gut are therefore immensely useful for understanding its function and associated ailments. In APL Bioengineering, by AIP Publishing, researchers from the University of California, Berkeley and Lawrence Berkeley National Lab described how gut-on-a-chip devices can bridge lab models and human biology.

Organ-on-a-chip devices are miniaturized models of human organs. They contain tiny microchannels where cells and tissue cultures interact with precisely controlled nutrients. Regulating the cell’s environment in such a way is crucial for creating realistic models of tissue.

Using these models avoids the time-consuming and costly challenges of clinical trials and the ethical issues behind animal testing.

“Medical research is currently facing major hurdles, both in terms of understanding the basic science governing the function of human organs and the research and development of new drugs and therapeutics,” said author Amin Valiei. “Access to valid models of human organs that can be studied conveniently in the lab can significantly accelerate scientific discoveries and the development of new medications.”

Modeling the microbiome is particularly difficult because of its unique environmental conditions. Through creative design, gut-on-a-chip devices can simulate many of these properties, such as the gut’s anaerobic atmosphere, fluid flow, and pulses of contraction/relaxation. Growing intestinal cells in this environment means that they more closely resemble human biology compared to standard laboratory cell cultures.

“Recent gut-on-a-chip models have demonstrated success in maintaining a viable coculture of the human intestinal cells and the microbiome for a few days and even up to weeks,” said Valiei. “This opens new ways to analyze the microbiome under biologically relevant conditions.”

The authors highlight key gut-on-a-chip devices and their success in simulating microbial and human cellular biology. They also describe current disease models and drug studies using the technology.

“Its unique capabilities make the organ-on-a-chip apt for plenty of research investigations in the future,” said Valiei.

The team is currently investigating dysbiosis, an imbalance in the gut microbial community with major health consequences. They aim to find innovative ways to diagnose, mitigate, and treat this condition.

Source:

American Institute of Physics

Microbiology

Scientists identify molecules in mucus that can block cholera infection

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Reviewed by Emily Henderson, B.Sc.Dec 13 2022

MIT researchers have identified molecules found in mucus that can block cholera infection by interfering with the genes that cause the microbe to switch into a harmful state.

These protective molecules, known as glycans, are a major constituent of mucins, the gel-forming polymers that make up mucus. The MIT team identified a specific type of glycan that can prevent Vibrio cholerae from producing the toxin that usually leads to severe diarrhea.

If these glycans could be delivered to the site of infection, they could help strengthen the mucus barrier and prevent cholera symptoms, which affect up to 4 million people per year. Because glycans disarm bacteria without killing them, they could be an attractive alternative to antibiotics, the researchers say.

Unlike antibiotics, where you can evolve resistance pretty quickly, these glycans don’t actually kill the bacteria. They just seem to shut off gene expression of its virulence toxins, so it’s another way that one could try to treat these infections.”

Benjamin Wang PhD ’21, one of the lead authors of the study

Julie Takagi PhD ’22 is also a lead author of the paper. Katharina Ribbeck, the Andrew and Erna Viterbi Professor of Biological Engineering at MIT, is the senior author of the study, which appears today in the EMBO Journal.

Other key members of the research team are Rachel Hevey, a research associate at the University of Basel; Micheal Tiemeyer, a professor of biochemistry and molecular biology at the University of Georgia; and Fitnat Yildiz, a professor of microbiology and environmental toxicology at the University of California at Santa Cruz.

Taming microbes

In recent years, Ribbeck and others have discovered that mucus, which lines much of the body, plays a key role in controlling microbes. Ribbeck’s lab has showed that glycans -; complex sugar molecules found in mucus -; can disable bacteria such as Pseudomonas aeruginosa, and the yeast Candida albicans, preventing them from causing harmful infections.

Most of Ribbeck’s previous studies have focused on lung pathogens, but in the new study, the researchers turned their attention to a microbe that infects the gastrointestinal tract. Vibrio cholerae, which is often spread through contaminated drinking water, can cause severe diarrhea and dehydration. Vibrio cholerae comes in many strains, and previous research has shown that the microbe becomes pathogenic only when it is infected by a virus called CTX phage.

“That phage carries the genes that encode the cholera toxin, which is really what’s responsible for the symptoms of severe cholera infection,” Wang says.

In order for this “toxigenic conversion” to occur, the CTX phage must bind to a receptor on the surface of the bacteria known as the toxin co-regulated pilus (TCP). Working with mucin glycans purified from the pig gastrointestinal tract, the MIT team found that glycans suppress the bacteria’s ability to produce the TCP receptor, so the CTX phage can no longer infect it.

The researchers also showed that exposure to mucin glycans dramatically alters the expression of many other genes, including those required to produce the cholera toxin. When the bacteria were exposed to these glycans, they produced almost no cholera toxin.

When Vibrio cholerae infects the epithelial cells that line the gastrointestinal tract, the cells begin overproducing a molecule called cyclic AMP. This causes them to secrete massive amounts of water, leading to severe diarrhea. The researchers found that when they exposed human epithelial cells to Vibrio cholerae that had been disarmed by mucin glycans, the cells did not produce cyclic AMP or start leaking water.

Delivering glycans

The researchers then investigated which specific glycans might be acting on Vibrio cholerae. To do that, they worked with Hevey’s lab to create synthetic versions of the most abundant glycans found in the naturally occurring mucin samples they were studying. Most of the glycans they synthesized have structures known as core 1 or core 2, which differ slightly in the number and type of monosaccharides they contain.

The researchers found that core 2 glycans played the biggest role in taming cholera infection. It is estimated that 50 to 60 percent of people infected with Vibrio cholerae are asymptomatic, so the researchers hypothesize that the symptomatic cases may occur when these cholera-blocking mucins are missing.

“Our findings suggest that maybe infections occur when the mucus barrier is compromised and is lacking this particular glycan structure,” Ribbeck says.

She is now working on ways to deliver synthetic mucin glycans, possibly along with antibiotics, to infection sites. Glycans on their own cannot attach to the mucosal linings of the body, so Ribbeck’s lab is exploring the possibility of tethering the glycans to polymers or nanoparticles, to help them adhere to those linings. The researchers plan to begin with lung pathogens, but also hope to apply this approach to intestinal pathogens, including Vibrio cholerae.

“We want to learn how to deliver glycans by themselves, but also in conjunction with antibiotics, where you might need a two-pronged approach. That’s our main goal now because we see so many pathogens are affected by different glycan structures,” Ribbeck says.

The research was funded by the National Institute of Biomedical Imaging and Bioengineering, the Materials Research Science and Engineering Centers Program of the U.S. National Science Foundation, the National Institute of Environmental Health Sciences, a Training Grant in Environmental Toxicology from the MIT Center for Environmental Health Sciences, the National Institutes of Health, and a Swiss National Science Foundation grant.

Source:

Massachusetts Institute of Technology

Journal reference:

Wang, B.X., et al. (2022) Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae. The EMBO Journal. doi.org/10.15252/embj.2022111562.

Microbiology

Improved early detection and analysis of airborne pathogens with new liquid-coated air filters

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Reviewed by Emily Henderson, B.Sc.Dec 7 2022

Researchers from the University of Maine and University of Massachusetts Amherst have designed new liquid-coated air filters that allow for improved early detection and analysis of airborne bacteria and viruses, including the one that causes COVID-19.

While conventional air filters help control the spread of disease in public spaces like hospitals and travel hubs, they struggle to keep the pathogens they capture viable for testing. The inefficiency can inhibit scientists’ ability to identify biological threats early on, which could hinder any response and protection measures.

The research team, led by Caitlin Howell, a UMaine associate professor of biomedical engineering, developed a composite membrane with a liquid layer for filters that is better suited for capturing viable bacterial and viral samples for analysis. They modeled the membrane after the Nepenthes pitcher plant, which has a slippery rim and inner walls that cause insects to fall and become trapped within its digestive fluid. By keeping the bacteria and viruses they capture feasible for examination, researchers say their novel liquid-coated air filters can enhance air sampling efforts, early pathogen detection and biosurveillance for national security.

I think for our patients and ourselves as caregivers, this technology will give us the confidence we are safer in performing care. Knowing we have improved safety makes it easier to leave our loved ones and go to work caring for others.”

Dr. Robert Bowie, Medical Director, Down East Emergency Medical Institute

The group of researchers developed multiple types of filters that contained their liquid-coated membrane technology, and tested their ability to preserve and release E. coli bacteria; SARS-COV-2, the virus that causes COVID-19; and JC polyomavirus, which attacks the central nervous system.

They specifically found that more airborne pathogens were captured by high efficiency particulate air (HEPA) filters with their liquid-coated membrane than those without. The team published their findings in the journal ACS Applied Materials & Interfaces.

“During the early stages of the pandemic we were watching in real time how many problems were being caused by no one knowing where the airborne virus was and where it wasn’t. We had a system that could start to address that need, so it was our responsibility to step up and help out,” Howell says.

The project was a significant interdisciplinary effort across the fields of biomedical engineering, chemical engineering and microbiology. The UMaine biomedical engineering team included first author and Susan J. Hunter Presidential Award winner Daniel Regan, Graduate School of Biomedical Science, Engineering (GSBSE) Ph.D. student Chun Ki Fong and former master’s student Justin Hardcastle. The microbiology team, led by associate professor Melissa Maginnis, included Avery Bond, a Ph.D. student in molecular and biomedical sciences, and Claudia Desjardins, then a university laboratory assistant in wastewater analysis. The chemical engineering team, based at UMass Amherst, consisted of professor Jessica Schiffman and Ph.D. student Shao-Hsiang Hung. The team was joined by Andrew Holmes, a biocontainment research scientist with University of Maine Cooperative Extension.

Regan first pitched the initial concept for liquid-coated air filters to capture bacteria-containing aerosols to his dissertation committee in March of 2019, based on conversations with military researchers and concerns for detecting potential contamination during medical evacuations. He also featured it in a presentation for the 2020 UMaine Student Symposium titled “Optimizing Liquid-Gated Membranes for Bioaerosol Capture and Release, which earned him the Dr. Susan J. Hunter Presidential Research Impact Award.

The concept was further developed and refined when Howell, Maginnis, Schiffman, and Holmes realized that this could also apply to virus-containing aerosols in the early days of the COVID-19 pandemic and applied for funding from the National Science Foundation. In 2020, the project was awarded a $225,000 NSF EAGER award -; an early concept grant that supports “untested, but potentially transformative research ideas or approaches.”

“COVID-19 has been a constant reminder of the important role biosurveillance capabilities provide for decision makers to have detailed information for reducing biological risks” says Regan, now a fellow at the Janne E. Nolan Center on Strategic Weapons, an institute of the Council on Strategic Risks in Washington, D.C. “In the last year alone, the world has experienced high-consequence pathogens including an outbreak of monkeypox (or mpox), a resurgence of Ebola Sudan and high case numbers of Respiratory Syncytial Virus Infection (RSV). The need for pathogen early warning could not be greater, and it is our hope that further investment in liquid-coated air filters can help advance biosurveillance capabilities for aerosol detection.”

Source:

University of Maine

Journal reference:

Regan, D.P., et al. (2022) Improved Recovery of Captured Airborne Bacteria and Viruses with Liquid-Coated Air Filters. ACS Applied Materials & Interfaces. doi.org/10.1021/acsami.2c14754.

Microbiology

Deep learning software helps to identify miniscule bacteria in microscopy images

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Reviewed by Emily Henderson, B.Sc.Oct 17 2022

Omnipose, a deep learning software, is helping to solve the challenge of identifying varied and miniscule bacteria in microscopy images. It has gone beyond this initial goal to identify several other types of tiny objects in micrographs.

The UW Medicine microbiology lab of Joseph Mougous and the University of Washington physics and bioengineering lab of Paul A. Wiggins tested the tool. It was developed by University of Washington physics graduate student Kevin J. Cutler and his team.

Mougous said that Cutler, as a physics student, “demonstrated an unusual interest in immersing himself in a biology environment so that he could learn first-hand about problems in need of solution in this field. He came over to my lab and quickly found one that he solved in spectacular fashion.”

Their results are reported in the Oct. 17 edition of Nature Methods.

The scientists found that Omnipose, trained on a large database of bacterial images, performed well in characterizing and quantifying the myriad of bacteria in mixed microbial cultures and eliminated some of the errors that can occur in its predecessor, Cellpose.

Moreover, the software wasn’t easily fooled by extreme changes in a cell’s shape due to antibiotic treatment or antagonism by chemicals produced during interbacterial aggression. In fact, the program showed that it could even detect cell intoxication in a trial using E. coli.

In addition, Omnipose did well in overcoming recognition problems due to differences in the optical characteristics across diverse bacteria.

Most bacteria are spheres or rods, but some have other basic forms, such as twisting spirals. Besides these, Omnipose could identify more elaborate bacteria with elongated shapes or with branches, filaments and appendages, all physical traits that can make it difficult for deep learning tools to suss out which bacteria are present in an image.

The program does still face some limitations in handling object overlap in a 2D rendition of a 3D sample of a crowded microbial community. Object overlap is what produces, for example, the effect of a clock on a wall giving the illusion of popping out of a person’s head in a photograph.

In analyzing cells in a root primordial data set from the fast-growing weed A. thaliana, Omnipose nonetheless did show some advantages over previous approaches in this 3D sample.

Other reviews by the Mougous lab team of Omnipose’s capabilities showed bacteria below a certain threshold in size can be hard for the tool to suss out.

Despite these drawbacks, the researchers believe that Omnipose could be a solution, they noted, to “help answer diverse questions in bacterial cell biology.”

To see if it could also become a multifunctional tool in other biological or even non-life sciences fields dependent on microscopy, the scientists tried out the program on micrographs of the ultra-tiny roundworm C. elegans, an important organism in genetic, neuroscience, developmental and microbial behavior research. Like some bacteria, this creature has an elongated shape. Like many other worms, it also can contort itself. Omnipose could pick out C. elegans regardless of its various stretches, contractions, and other movements. This ability could be useful, for instance, in neural studies of C. elegans locomotion during time-lapse tracking.

In designing tools like Omnipose, researchers are looking at a scale of single-pixel precision to define the boundaries of a cell. That’s because most bacterial cell body images are composed of only a small number of pixels. The researchers explained that defining boundaries within an image is called segmentation. They developed Ominpose through a deep neural-network, high precision segmentation algorithm. Their experiments showed Omnipose has an unprecedented segmentation accuracy.

The scientists designed designed Omnipose for use by typical research laboratories and made its source code, training data and models publicly available, along with documentation on how to use the program.

“We anticipate that the high performance of Omnipose across varied cellular morphologies and modalities,” the researchers wrote in their report,” may unlock information from microscopy images that was previously inaccessible.”

Reflecting the importance of the problem, this is a crowded field. Yet Kevin’s solution stands out from the pack. We believe it will be a game-changer for biological image analysis”

Joseph Mougous, UW Medicine

In addition to Cutler, Wiggins and Mougous, other researchers on the Omnipose testing project were Carsen Stringer, Teresa W. Lo, Luca Rappez, Nicholas Stroustrup. S. Brooke Peterson, and Paul Wiggins. Mougous is a Howard Hughes Medical Institute investigator.

Source:

University of Washington School of Medicine/UW Medicine

Journal reference:

Cutler, K.J., et al. (2022) Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation. Nature Methods. doi.org/10.1038/s41592-022-01639-4.

Microbiology

Genetically engineered bacteria make living materials for self-repairing walls and cleaning up pollution

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With just an incubator and some broth, researchers can grow reusable filters made of bacteria to clean up polluted water, detect chemicals in the environment and protect surfaces from rust and mold.

I am a synthetic biologist who studies engineered living materials – substances made from living cells that have a variety of functions. In my recently published research, I programmed bacteria to form living materials that can not only be modified for different applications, but are also quick and easy to produce.

Like human cells, bacteria contain DNA that provides the instructions to build proteins. Bacterial DNA can be modified to instruct the cell to build new proteins, including ones that don’t exist in nature. Researchers can even control exactly where these proteins will be located within the cell.

Because engineered living materials are made of living cells, they can be genetically engineered to perform a broad variety of functions, almost like programming a cellphone with different apps. For example, researchers can turn bacteria into sensors for environmental pollutants by modifying them to change color in the presence of certain molecules. Researchers have also used bacteria to create limestone particles, the chemical used to make Styrofoam and living photovoltaics, among others.

A primary challenge for engineered living materials has been figuring out how to induce them to produce a matrix, or substances surrounding the cell, that allows researchers to control the physical properties of the final material, such as its viscosity, elasticity and stiffness. To address this, my team and I created a system to encode this matrix in the bacteria’s DNA.

We modified the DNA of the bacteria Caulobacter crescentus so that the bacterial cells would produce on their surfaces a matrix made of large amounts of elastic proteins. These elastic proteins have the ability to bind to each other and form hydrogels, a type of material that can retain large amounts of water.

When two genetically modified bacterial cells come in close proximity, these proteins come together and keep the cells attached to each other. By surrounding each cell with this sticky, elastic material, bacterial cells will cluster together to form a living slime.

Furthermore, we can modify the elastic proteins to change the properties of the final material. For example, we could turn bacteria into hard construction materials that have the ability to self-repair in the event of damage. Alternatively, we could turn bacteria into soft materials that could be used as fillers in products.

Usually, creating multifunctional materials is extremely difficult, due in part to very expensive processing costs. Like a tree growing from a seed, living materials, on the other hand, grow from cells that have minimal nutrient and energy requirements. Their biodegradability and minimal production requirements allow for sustainable and economical production.

The technology to make living materials is unsophisticated and cheap. It only takes a shaking incubator, proteins and sugars to grow a multifunctional, high-performing material from bacteria. The incubator is just a metal or plastic box that keeps the temperature at about 98.6 degrees Fahrenheit (37 Celsius), which is much lower than a conventional home oven, and shakes the cells at speeds slower than a blender.

Transforming bacteria into living materials is also a quick process. My team and I were able to grow our bacterial living materials in about 24 hours. This is pretty fast compared to the manufacturing process of other materials, including living materials like wood that can take years to produce.

Moreover, our living bacterial slime is easy to transport and store. It can survive in a jar at room temperature for up to three weeks and placed back into a fresh medium to regrow. This could lower the cost of future technology based on these materials.

Lastly, engineered living materials are an environmentally friendly technology. Because they are made of living cells, they are biocompatible, or nontoxic, and biodegradable, or naturally decomposable.

There are still some aspects of our bacterial living material that need to be clarified. For example, we don’t know exactly how the proteins on the bacterial cell surface interact with each other, or how strongly they bind to each other. We also don’t know exactly how many protein molecules are required to keep cells together.

Answering these questions will enable us to further customize living materials with desired qualities for different functions.

Next, I’m planning to explore growing different types of bacteria as living materials to expand the applications they can be used for. Some types of bacteria are better than others for different purposes. For example, some bacteria survive best in specific environments, such as the human body, soil or fresh water. Some, on the other hand, can adapt to different external conditions, like varying temperature, acidity and salinity.

By having many types of bacteria to choose from, researchers can further customize the materials they can create.


Sara Molinari

The Conversation