The scientific thrill of uncovering the world’s biggest bacteria
On June 23, 2022, a team of scientists funded in part by the Gordon and Betty Moore Foundation announced the discovery of the largest species of bacteria ever identified – Ca. Thiomargarita magnifica.
In a study published in the journal Science, researchers describe the massive bacterium as being nearly a centimeter in size, thousands of times bigger than bacteria such as E. coli, with dimensions similar to a human eyelash. Cells of most bacterial species are around 2 microns in length, with some of the largest specimens reaching 750 microns. Thiomargarita magnifica has an average cell length greater than 9,000 microns. Jean-Marie Volland, Ph.D., lead author of the paper, described the magnitude of the difference as, “like meeting a human as large as Mount Everest.” The finding is a result of a large body of work conducted by an international team of scientists investigating many aspects of the bacteria.
“This groundbreaking discovery highlights the importance of supporting fundamental, creative research projects to advance our understanding of the natural world,” said Sara Bender, Ph.D., program officer for Science at the Gordon and Betty Moore Foundation. “We look forward to learning how the characterization of Thiomargarita magnifica challenges the current paradigm of what constitutes a bacterial cell and advances microbial research.”
The discovery: Breaking the rules of life
It was in a Caribbean mangrove forest that Olivier Gros, Ph.D., a senior author on the paper, first noticed the bacteria. Bacterial filaments resembled small white threads that together coated leaves rotting in the water. They had no idea what the organisms were, with the initial assumption being they were likely tiny sponges or fungi. It was only after analyzing the DNA did Silvina Gonzalez-Rizzo, Ph.D., a researcher in Gros’ lab, realized that they were looking at bacteria unlike any they had previously seen.
The bacteria’s unprecedented size isn’t its only attribute surprising researchers. It appears Thiomargarita magnifica also possesses a far more sophisticated structure than seen in typical bacteria.
Filaments of Ca. Thiomargarita magnifica. Image 1 by Jean-Marie Volland. Image 2 by Olivier Gros.
For many decades now, scientists have considered bacteria to be simple, single-celled organisms with no nuclei – certainly too simple to produce large cells.
Eukaryotes, such as large animals, have much more complex cells that contain a nucleus and organelles like mitochondria. Eukaryotic cells have adapted in ways that allow them to grow larger – including the evolution of a robust molecular structure and membrane that keep them from falling apart as they grow. While views about bacteria are slowly changing, they are not typically thought to have such adaptations.
Researchers were therefore surprised to discover evidence of more complex structural and functional structures – echoes of eukaryotic cells – in Thiomargarita magnifica. While a bacterial cell has just one loop of DNA that floats freely, Thiomargarita magnifica has hundreds of thousands of them, grouped and tucked inside tiny compartments. The researchers refer to these compartments as “pepins”, resembling small seeds in fruits like a kiwi. Pepins are reminiscent of nuclei in more complex eukaryotic cells, acting like factories to build proteins from DNA.
The ability to make proteins from its massive supply of DNA may be what enables the bacteria to grow so large.
There’s yet another departure Thiomargarita magnifica makes from most bacteria, which reproduce by dividing one cell into two: Each giant, filament-like cell appears instead to reproduce by breaking off a piece of itself at the tip. That segment can then separate and create a whole new cell.
The team notes that many more aspects of the bacterium’s biology will become clearer over the coming months as they continue their investigations.
Matchmaking: grantee, funder, and funding
In 2019, the Moore Foundation funded Stanford University with a subaward to the Laboratory for Research in Complex Systems (formerly Global Viral), as part of a project called the Boundaries of Life (BoL) Research Initiative. BoL is a collaboration of scientists working on developing new assays and tools to scan diverse ecological niches on earth to identify hidden, novel forms of life - sometimes also referred to as “shadow life.”
“The team’s scientific vision was immediately evident from the proposal – a unique, high-risk, high-reward, discovery-focused collaboration to explore shadow life,” said Bender. “It brought together accomplished scientists from various institutions and disciplines to gain a broader, better, and deeper understanding of life on earth and possibly other extraterrestrial environments.”
The proposal also aligned well with the Moore Foundation’s initiatives in Marine Microbiology and Symbiosis in Aquatic Systems, testing the power of technology, innovation, and collaboration to study the unseen microbial world.
“From a funding perspective, we acknowledge that exploratory research to answer life’s most fundamental questions can be risky, but curiosity-driven exploration is essential for learning about our world – and there are many mysteries yet to uncover,” added Bender.
Notably, the funding in 2019 afforded the scientists the time and space to see where the science took them, ultimately leading them to Thiomargarita magnifica.
“We are thankful that the Moore Foundation recognized the merit and potential of our high-risk work, and for Sara’s patience as we explored,” said grantee Shailesh Date, Ph.D., CEO of Laboratory for Research in Complex Systems and one of the authors on the Thiomargarita magnifica paper. “This project is an exemplar of alignment between the funder and grantee’s vision of undertaking challenging, non-incremental projects that can significantly transform the research landscape for generations to come.”