E.coli Optimism

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.

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."

Sophia Hsin-Jung Li, Zhiyuan Li, Junyoung O. Park, Christopher G. King, Joshua D. Rabinowitz, Ned S. Wingreen, Zemer Gitai. Escherichia coli translation strategies differ across carbon, nitrogen and phosphorus limitation conditions. Nature Microbiology, 2018; DOI: 10.1038/s41564-018-0199-2