Largest bacterium ever discovered has unexpectedly complex cells

By definition, microbes are supposed to be so small they can only be seen with a microscope. But a newly described bacterium living in Caribbean mangroves never got that memo (see video, above). Its threadlike single cell is visible to the naked eye, growing up to 2 centimeters—as long as a peanut—and 5000 times bigger than many other microbes. What’s more, this giant has a huge genome that’s not free floating inside the cell as in other bacteria, but is instead encased in a membrane, an innovation characteristic of much more complex cells, like those in the human body.

The bacterium was unveiled in a preprint posted online last week and it has astounded some researchers who have reviewed its features. “When it comes to bacteria, I never say never, but this one for sure is pushing what we thought was the upper limit [of size] by 10-fold,” says Verena Carvalho, a microbiologist at the University of Massachusetts, Amherst.

The discovery is “fantastic and eye-opening,” adds Victor Nizet, a physician scientist at the University of California, San Diego, who studies infectious diseases. The oversize bacterium is bigger than fruit flies and nematodes, common lab organisms that he and others sometimes infect with much smaller bacteria for their research.

Aside from upending ideas about how big—and sophisticated—microbes can become, this bacterium “could be a missing link in the evolution of complex cells,” says Kazuhiro Takemoto, a computational biologist at Kyushu Institute of Technology.

Researchers have long divided life into two groups: prokaryotes, which include bacteria and single-cell microbes called archaea, and eukaryotes, which include everything from yeast to most forms of multicellular life, including humans. Prokaryotes have free-floating DNA, whereas eukaryotes package their DNA in a nucleus. Eukaryotes also compartmentalize various cell functions into vesicles called organelles and can move molecules from one compartment to another—something prokaryotes can’t.

But the newly discovered microbe blurs the line between prokaryotes and eukaryotes. About 10 years ago, Olivier Gros, a marine biologist at the University of the French Antilles, Pointe-à-Pitre, came across the strange organism growing as thin filaments on the surfaces of decaying mangrove leaves in a local swamp. Not until 5 years later did he and his colleagues realize the organisms were actually bacteria. And they didn’t appreciate how special the microbes were until more recently, when Gros’s graduate student Jean-Marie Volland took up the challenge of trying to characterize them.

Some microbes, such as slime molds and blue-green algae, form visible stalks or filaments composed of stacks of cells, but the group used a variety of microscopy and staining methods to verify the mangrove filaments were each just one cell. This “was something we didn’t believe … at first,” recalls Volland, now a marine biologist at Lawrence Berkeley National Laboratory. 

Furthermore, that cell includes two membrane sacs, one of which contains all the cell’s DNA, Volland and colleagues report in their 18 February preprint on bioRxiv. Volland calls that sac an organelle and that’s “a big new step” that implies the two branches of life are not as different as previously thought, Carvalho says. “Perhaps it’s time to rethink our definition of eukaryote and prokaryote!” agrees Petra Levin, a microbiologist at Washington University in St Louis. “It’s a supercool story.”

The other, water-filled sac may be the reason the bacterium could grow so big. Microbiologists used to think bacteria had to be small, in part because they eat, breathe, and get rid of toxins by diffusion of molecules through their cell’s interior and there are limits to how great a distance these molecules can travel. Then in 1999, researchers discovered a giant sulfur-eating microbe roughly the size of a poppy seed off Namibia’s coast. It can be big because its cellular contents are squished up against its outer cell wall by a giant water- and nitrate-filled sac. The bacteria’s essential molecules can still diffuse in and out because “only [along the edge] is the cell living,” says Carvalho, who worked on this group of bacteria. Scientists have since found other large sulfur-eating bacteria, but their long filaments consist of multiple cells.      

Like the microbe found in Namibia, the new mangrove bacterium also has a huge sac—presumably of water—that takes up 73% of its total volume. That similarity and a genetic analysis led the research team to place it in the same genus as most of the other microbial giants and propose calling it Thiomargarita magnifica.

“What an excellent name!” says Andrew Steen, a bioinformatician at the University of Tennessee, Knoxville, who studies how microorganisms affect geochemical cycles. “Reading about it makes me feel exactly the same way as when I hear about an enormous dinosaur, or some celestial structure that is impossibly large or hot or cold or dense or weird in some way.”

The largest T. magnifica cell Volland found was 2 centimeters tall, but Carvalho thinks that if not trampled, eaten, blown by wind, or washed away by a wave, they could grow even bigger.

The DNA-filled sac, also squished along the inner edge of this bacterium, proved extraordinary as well. When researchers at the Department of Energy Joint Genome Institute sequenced the DNA inside, they found the genome was huge, with 11 million bases harboring some 11,000 clearly distinguishable genes. Typically, bacterial genomes average about 4 million bases and about 3900 genes.

By labeling the DNA with fluorescent tags, Volland determined the bacterium’s genome was so big because there are more than 500,000 copies of the same stretches of DNA. Protein production factories called ribosomes were inside the DNA-filled sac as well, likely making the translation of a gene’s code into a protein more efficient. “Separating genetic material from everything else allows more sophisticated control and greater complexity,” says Chris Greening, a microbiologist at Monash University, Clayton.

“All too often, bacteria are thought of as small, simple, ‘unevolved’ life forms—so-called ‘bags of proteins,’” Greening adds. “But this bacterium shows this couldn’t be much further from the truth.”