Nav: Home

Princeton researchers discover the 'optimism' of E. coli bacteria

July 23, 2018

Princeton researchers discover the 'optimism' of E. coli bacteria

By Liz Fuller-Wright, Princeton University Office of Communications

A team of researchers from across the Princeton University campus collaborated to determine how E. coli bacteria respond when they are deprived of three key nutrients: carbon, nitrogen and phosphorus.

They were surprised to find that the bacteria had different strategies for dealing with each of the nutrient restrictions. Even more surprisingly, when carbon was limited, E. coli responded by building up its protein-production infrastructure, essentially preparing for a day when carbon would again be abundant.

"E. coli has that essential optimism -- it expects it will have access to more carbon in the future," said Zemer Gitai, the Edwin Grant Conklin Professor of Biology and a senior author on a paper released online July 23 from Nature Microbiology. All seven of the co-authors are Princeton scientists, from six departments.

It can help to think of the cell as a toy factory filled with individual assembly lines (ribosomes) producing toys (proteins), Gitai said. Carbon and nitrogen are key components of the toys, and phosphorus is vital to the assembly lines.

"When resources get tight, the cell has a decision to make," Gitai said. "What's the right usage of materials -- of its available resources? 'Am I going to devote resources into making more assembly lines or more toys?'"

The "toys," proteins, are the fundamental building blocks that allow cells to grow, divide or increase in mass. The faster a cell produces proteins, the faster it grows. Scientists have known for decades that there is a straightforward, linear relationship between the number of ribosomes (assembly lines) and the rate of protein (toy) production in E. coli. This has led to the widely accepted theory that each of these assembly lines is "optimized," operating constantly at its peak efficiency to produce proteins as fast as possible.

"Surprisingly, the current study radically changes this perspective," said Ned Wingreen, the Howard A. Prior Professor in the Life Sciences and a professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics (LSI) who was also a corresponding author on the paper.

The research team discovered that when they limited access to carbon and nitrogen, key ingredients in the toys, the cells grew slowly but steadily while also producing more and more assembly lines that sat idle.

"Under extreme carbon limitation, about half the ribosomes -- half the assembly lines -- are not even working," said Gitai. "That seems counterintuitive, right? That seems wasteful. Why build your factory so you have twice as many assembly lines as you need, and then not run half your assembly lines? We posited that that might be good for ramping up production when times change, and sure enough, that's what we saw."

These bacteria live in feast-or-famine environments like the human gut, where a long hungry period can end with the sudden arrival of a cheeseburger. "When all these new nutrients come in, you have the ability to produce faster," Gitai said. "You already made all those assembly lines -- they're ready, and now they can take off, now you can beat your competitors to the punch, because you don't have to invest in all this infrastructure, making all these new assembly lines. You have them set up."

This has interesting implications for E. coli competition strategies, said graduate student Hsin-Jung (Sophia) Li, who is the first author on the paper. "Maybe the goal of the bacteria is not to maximize the current growth," she said. "They might be preparing for better times -- more forward-looking."

"Overall, this work gives a new perspective on bacteria, and potentially other organisms, suggesting they evolved not only to deal with current conditions but also for life in a changing world," said Wingreen.

"It has been an exciting journey," said Junyoung Park, a 2016 Ph.D. graduate in chemical and biological engineering who is now a professor of chemical and biomolecular engineering at the University of California-Los Angeles. "We started with a simple observation -- nutrient-specific RNA-to-protein ratios -- but ended up with fascinating insights into the cell's competition strategies."

E. coli uses different strategies when different nutrients are limited, the researchers found. "Carbon-limited cells generate a large number of inactive assembly lines," Li said. "Nitrogen-limited cells turn out products more slowly. But phosphorous-limited cells -- this was the exciting part -- use only half as many assembly lines to generate the same number of toys."

The ribosome assembly lines depend on RNA, which is phosphorus-rich, so by limiting its availability, the researchers essentially made toy ingredients cheap but assembly lines very expensive.

"The first surprise was that there's a nutrient-specific story here, that we achieved the same growth rate three different ways," said Gitai. "But the real surprise was the phosphorus. We found that if we make the assembly lines more expensive, suddenly the same assembly lines can pump out toys at the same rate, using half as many assembly lines. That tells us that under the carbon- and nitrogen-limited conditions, those assembly lines were actually not working as fast as they possibly could."

This overturned the long-held model of the optimized ribosome and prompted the researchers to investigate the mechanisms at work in the ribosomes, using a combination of quantitative experiments, led by Li, buttressed by the modeling and theory work of Wingreen and Zhiyuan Li, an associate research scholar in the Princeton Center for Theoretical Science. They also collaborated with Christopher King, who graduated in 2017 with a physics concentration, and Joshua Rabinowitz, a professor of chemistry and LSI.

Converting the enormous quantities of biological data into a clear theory illustrates the "charm" of data science, said Zhiyuan Li, from processing the measurements into "individual pearls, and then stringing them together into a beautiful necklace by mathematical modeling that reveals the underlying connections."

"This paper is a great contribution to the community," said Ron Milo, principal investigator of the Department of Plant and Environmental Sciences at the Weizmann Institute of Science, who was not involved in this research. "It gives us better insight into how cells make decisions regarding their allocation of resources, which can be relevant for biotechnological production of value-added chemicals."

The research also raises a new question, said Gitai: "Do many bacterial species use this strategy? You could imagine that in a community of bacteria, there are some species that are optimists, some that are pessimists. ... It's kind of an appealing idea that it's this 'eternal optimism' of E. coli that allows it to trade off, if you will, between immediate benefit and the longer term. When times are bad, it's going to say, 'Okay, I'm not going to worry about doing as well as I possibly can right now, but I'll prepare for when times get better.'"

One of the biggest surprises of the research was that such a thoroughly studied bacteria still has tricks up its microscopic sleeves, said Sophia Li. "Even E. coli, arguably the most well-understood organism, can still give us new surprises and interesting biology to learn."
"E. coli translation strategies differ across carbon, nitrogen, and phosphorus limitation conditions," by Hsin-Jung (Sophia) Li, Zhiyuan Li, Junyoung Park, Christopher King, Joshua Rabinowitz, Ned Wingreen and Zemer Gitai, appears in Nature Microbiology on July 23, DOI: 10.1038/s41564-018-0199-2. The research was supported by two grants from the National Institutes of Health (DP1AI124669 and R01GM082938).

Princeton University

Related Bacteria Articles:

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.
Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.
Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.
Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.
Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.
How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.
The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?
Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.
Bacteria uses viral weapon against other bacteria
Bacterial cells use both a virus -- traditionally thought to be an enemy -- and a prehistoric viral protein to kill other bacteria that competes with it for food according to an international team of researchers who believe this has potential implications for future infectious disease treatment.
Drug diversity in bacteria
Bacteria produce a cocktail of various bioactive natural products in order to survive in hostile environments with competing (micro)organisms.
More Bacteria News and Bacteria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at