A large complex of proteins (various colors) pulls the membrane of a bacterium outward to help propel the bacterium forward.

Researchers begin to reveal bacteria's sophisticated architecture; they just needed the right tools for the job.

Bacteria have not gotten the respect they deserve. For decades, scientists saw them as mere bags of enzymes that lack the internal order and complexity of eukaryotic cells like ours.

But recent findings by Christine Jacobs-Wagner of Yale University and Grant Jensen of the California Institute of Technology (Caltech)—among others—have undermined that simplistic stereotype. “Bacteria are a lot more like eukaryotic cells than we thought,” says Jensen.

He and Jacobs-Wagner, who both became HHMI investigators in 2008 and frequently collaborate, have revealed that bacteria are surprisingly sophisticated and well-organized. Their work has shown how this unanticipated order shapes cells and helps them grow, divide, and move, among other vital activities.

		Bacterial Scaffolding See examples of bacterial structures that HHMI investigator Grant Jensen has discovered.

“Before, it was a blur, but now we are starting to see things clearly,” says Jacobs-Wagner. What's also clear, both scientists agree, is that the benefits of knowing bacteria better could range from medicine to efforts to curb global warming.

Earlier scientists had good reason to think that bacteria were simple, says Jacobs-Wagner. Even the most powerful electron microscopes showed little internal structure. But bacterial architecture came into focus thanks to technologies like fluorescence light microscopy and electron cryotomography (ECT). (See sidebar, “Detailing Bacteria.”)

Jacobs-Wagner first glimpsed microbial order during her postdoc work at Stanford University in the late 1990s. She was investigating a bacterial enzyme that helps control cell division. When she and her colleagues tracked the protein using a fluorescent tag, they found it was initially spread evenly around the bacterial cell membrane. But shortly before division it collected near one tip, suggesting that its location influenced the cell's actions. “That opened our eyes that perhaps there was a lot of structural organization in [bacterial] cells that we hadn't expected.”

More of that organization came to light when, after she joined the faculty at Yale in 2001, Jacobs-Wagner and colleagues uncovered a key part of the bacterial cytoskeleton. In eukaryotes, this mesh of protein filaments supports a cell somewhat like bones support our bodies. Eukaryotic cells continually rebuild and reorganize their cytoskeleton, so they can crawl, capture food, and divide. For years, experts thought that bacteria didn't have one. But in the 1990s and early 2000s, researchers identified bacterial versions of two of the three main types of proteins that form cytoskeleton filaments—actin and tubulin. Then in 2003, Jacobs-Wagner and colleagues discovered that some bacteria carried a protein they called crescentin that was equivalent to building blocks that form the third filament type, known as an intermediate filament.

Image: Molecular Macrobiology, Vol. 60, Issue 2, cover. Reprinted with permission of John Wiley & Sons, Inc.

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