Tag: Bacteria

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Bacterial ‘Fight Clubs’ and the Search for New Medicines

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Competition encourages bacteria to produce secondary metabolites with therapeutic potential that they would otherwise hold in reserve. Credit: Michael Smeltzer, Vanderbilt University.

Bacteria hold a vast reservoir of compounds with therapeutic potential. They use these compounds, known as secondary metabolites, to protect themselves against their enemies. We use them in many antibiotics, anti-inflammatories and other treatments.

Scientists interested in developing new medicines have no shortage of places to look for secondary metabolites. There are an estimated 120,000 to 150,000 bacterial species on Earth. Each species is capable of producing hundreds of secondary metabolites, but often only under specific ecological conditions. The challenge for researchers is figuring out how to coax the bacteria to produce these compounds.

Now, Brian Bachmann and John McLean of Vanderbilt University and their teams have shown that by creating “fight clubs” where bacteria compete with one another, they can trigger the bacteria to make a wide diversity of molecules, including secondary metabolites. Continue reading “Bacterial ‘Fight Clubs’ and the Search for New Medicines”

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The Simple Rules Bacteria Follow to Survive

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Left: Football stadium. Right: Colored contoured lines showing the periodic stops in the growth of a bacterial colony
Football image credit: Stock image. The colored contoured lines show the periodic stops in the growth of a bacterial colony. Credit: Süel Lab, UCSD.

What do these images of football fans and bacterial cells have in common? By following simple rules, each individual allows the group to accomplish tasks none of them could do alone—a stadium wave that ripples through the crowd or a cell colony that rebounds after antibiotic treatment.

These collective behaviors are just a few examples of what scientists call emergent phenomena. While the reasons for the emergence of such behavior in groups of birds, fish, ants and other creatures is well understood, they’ve been less clear in bacteria. Two independent research teams have now identified some of the rules bacterial cells follow to enable the colony to persist. Continue reading “The Simple Rules Bacteria Follow to Survive”

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Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy

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Sarkis K. Mazmanian
Credit: New York Academy of Sciences
Sarkis K. Mazmanian, Ph.D.
Born in: The country of Lebanon, moved to Los Angeles when he was 1
Fields: Microbiology, immunology, neuroscience
Works at: California Institute of Technology
Awards won: Many, including the MacArthur Foundation “Genius” grant
Most proud of: The success of his trainees! “There’s nothing that comes close to the gratification and joy I feel when a student or research fellow goes on to be an independent scientist.”
When not in the lab or mentoring students, he’s: Spending time with his family, including his 1-year-old-son or going for an occasional run

As a child, Sarkis Mazmanian frequently took things apart to figure out how they worked. At the age of 12, he dismantled his family’s entire television set—to the dismay of his parents and the unsuccessful TV repairman.

“I wasn’t aware of this at the time, but maybe that was some sort of a foreshadowing that I would enjoy science,” Mazmanian says. “Scientists take biological systems apart to understand how they work.”

Mazmanian never thought he’d become a microbiologist, let alone a leading expert in the field. He began studying microbiology at the University of California, Los Angeles (UCLA), because it was the major that allowed him to do the most hands-on research. But as soon as he entered the field, he fell in love with the complexities of microbial organisms and the efficiency of their functions. Continue reading “Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy”

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Meet Karen Carlson

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Karen Carlson
Credit: Karen Carlson
Karen Carlson
Fields: Systems biology, bacterial biofilms
Born and raised in: Alaska
Undergraduate student at: The University of Alaska, Anchorage
When not in the lab, she’s: Out and about with her 3-year-old son, friends and family
Secret talent: “I make some really good cookies.”

Karen Carlson got a surprise in her 10th grade biology class. Not only did she find out that she enjoyed science (thanks to an inspiring teacher), but, as she puts it, “I realized that I was really good at it.”

In particular, she says, “I was good at putting all the pieces [of a scientific question] together. And that’s what I had the most fun with—looking at systems: how things fit together and the flow between them.”

These are perfect interests for a budding systems biologist, which is what Carlson is on her way to becoming. She’s a senior in college on track to graduate this year with a bachelor’s degree in biology from the University of Alaska, Anchorage (UAA). Next, she plans to enroll in a master’s degree program at UAA, and eventually to pursue a Ph.D. in a biomedical field. Continue reading “Meet Karen Carlson”

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E. Coli Bacteria as Medical Sensors and Hard Drives?

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E.Coli
Modified E. coli bacteria can serve as sensors and data storage devices for environmental and medical monitoring. Credit: Centers for Disease Control and Prevention. View larger image

E. coli bacteria help us digest our food, produce vitamin K and have served as a model organism in research for decades. Now, they might one day be harnessed as environmental or medical sensors and long-term data storage devices Exit icon.

MIT researchers Timothy Lu and Fahim Farzadfard modified the DNA of E. coli cells so that the cells could be deployed to detect a signal (for example, a small molecule, a drug or the presence of light) in their surroundings. To create the modified E. coli, the scientists inserted into the bacteria a custom-designed genetic tool.

When exposed to the specified signal, the tool triggers a series of biochemical processes that work together to introduce a single mutation at a specific site in the E. coli’s DNA. This genetic change serves to record exposure to the signal, and it’s passed on to subsequent generations of bacteria, providing a continued record of exposure to the signal. In essence, the modified bacteria act like a hard drive, storing biochemical memory for long periods of time. The memory can be retrieved by sequencing the bacteria or through a number of other laboratory techniques.

Continue reading “E. Coli Bacteria as Medical Sensors and Hard Drives?”
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Modifying Bacterial Behavior

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Biofilm
Communication through quorum sensing is key to the formation of biofilms, slimy bacterial communities that can cause infections and are often stubbornly resistant to antibiotics. Credit: P. Singh and E. Peter Greenberg.

Like a person trailing the aroma of perfume or cologne, bacteria emit chemical signals that let other bacteria of the same species know they’re there. Bacteria use this chemical communication system, called quorum sensing, to assess their own population size. When they sense a large enough group, or quorum, the microbes modify their behavior accordingly. Many disease-causing bacteria use quorum sensing to launch a coordinated attack when they’ve amassed in sufficient numbers to overwhelm the host’s immune response.

Chemist Helen Blackwell of the University of Wisconsin-Madison has been making artificial compounds that mimic natural quorum-sensing signals, as well as some that block a natural signal from binding to its protein target—a step needed to produce a change in bacterial behavior. By altering key building blocks in these protein targets one by one, Blackwell’s team found that small changes could convert an activation signal into an inhibitory signal, or vice versa, indicating that small-molecule control of quorum sensing is very finely tuned.

Improved understanding of the molecular basis of quorum sensing could help scientists design more potent compounds to disrupt these signals. Using such compounds to quiet quorum sensing may provide a new way to control disease-causing bacteria that reduces the chances an infection will become resistant to treatment.

This work was funded in part by NIH under grants R01GM109403 and T32GM008505.

Learn more:
University of Wisconsin-Madison News Release Exit icon
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Outwitting Antibiotic Resistance

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Marine scene with fish and corals
The ocean is a rich source of microbes that could yield infection-fighting natural molecules. Credit: National Oceanic and Atmospheric Administration Exit icon.

Antibiotics save countless lives and are among the most commonly prescribed drugs. But the bacteria and other microbes they’re designed to eradicate can evolve ways to evade the drugs. This antibiotic resistance, which is on the rise due to an array of factors, can make certain infections difficult—and sometimes impossible—to treat.

Read the Inside Life Science article to learn how scientists are working to combat antibiotic resistance, from efforts to discover potential new antibiotics to studies seeking more effective ways of using existing ones.

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Restoring the Function of an Immune Receptor Involved in Crohn’s Disease

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Gut bacteria
Receptor proteins bind to bacterial cell wall fragments, initiating an immune response to remove bad gut bacteria. Credit: S. Melanie Lee, Caltech; Zbigniew Mikulski and Klaus Ley, La Jolla Institute for Allergy and Immunology.

Our bodies depend on a set of immune receptors to remove harmful bacteria and control the growth of helpful bacteria in our guts. Genetic changes that alter the function of the receptors can have an adverse effect and result in chronic inflammatory diseases like Crohn’s disease. Catherine Leimkuhler Grimes and Vishnu Mohanan of the University of Delaware researched a Crohn’s-associated immune receptor, NOD2, to figure out how it can lose the ability to respond properly to bacteria. In the process, they identified the involvement of a protective protein called HSP70. Increasing HSP70 levels in kidney, colon and white blood cells appeared to restore NOD2 function. This work represents a first step toward developing drugs to treat Crohn’s disease.

This work was funded in part by an Institutional Development Award (IDeA) Network of Biomedical Research Excellence (INBRE) grant.

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Carbohydrates as Bacterial Camouflage: How Our Immune System Responds

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bacteria
Although invisible to our immune system’s antibodies, strains of a pneumonia-causing bacteria, Pseudomonas aeruginosa (orange), are easily detected by galectins. Credit: Centers for Disease Control and Prevention.

When harmful strains of bacteria invade our bodies, our immune system produces antibodies that identify the intruders by the specific carbohydrate structures coating them. Some strains, however, have coatings that mimic the carbohydrate structures found on our own cells, and this disguise allows them to evade detection by antibodies.

A team of scientists led by Richard Cummings of Emory University found that galectins, a class of proteins naturally produced by our bodies, can identify and kill these concealed bacteria without damaging our own mimicked cells. To make this discovery, the team used glass slides covered with more than 300 different carbohydrates extracted from the surface of bacterial cells. After testing the ability of galectins and antibodies to bind to specific carbohydrates on these slides, the researchers observed that the galectins easily detected the mammalian-like carbohydrates that the antibodies failed to recognize.

These findings provide a clearer understanding of the complementary roles played by galectins and antibodies in protecting us from a broad range of infections.

This work also was funded by NIH’s National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute.

Learn more:
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On the Trail of Drug-Defying Superbugs

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Antibiotic-resistant strains of Staphlyococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH’s National Institute of Allergy and Infectious Diseases.
Antibiotic-resistant strains of Staphlyococcus aureus bacteria (purple) have become the most common cause of skin infections seen in hospital emergency departments. Credit: NIH’s National Institute of Allergy and Infectious Diseases.

In the United States alone, at least 2 million people each year develop serious infections with bacteria that have become resistant to the antibiotics we use to combat them, and about 23,000 die, according to the Centers for Disease Control and Prevention. Antibiotic resistance can turn once-manageable infections into “superbug” diseases that are difficult—and sometimes impossible—to treat.

Scientists funded by the National Institutes of Health are studying many aspects of antibiotic resistance, including how it spreads. Read this Inside Life Science article for just a few research examples and how the work could aid efforts to curb the emergence of resistance.