by Jennifer Frazer

Crawling around on the mucousy surfaces of your mouth, throat, lungs, urethra, and — if you have one, vagina — are the tiniest free-living cells known to science: Mycoplasmas.

Mycoplasmas are bacteria that lack cell walls and live in humans and other animals. They are not only the tiniest free-living cells we know of, but they also have the fewest genes. What makes them so small and so simple is their past: they jumped on the animal train a long, long time ago, and they have never gotten off. Thanks to hundreds of millions of years of co-evolution, they have gotten so good at making themselves at home in and taking what they need from us that they have made minimal living into an art form.

These bacteria aren’t just strange for their microscopic (even by microscopic standards) size, they are weirdos in lots of other ways, too. Unlike most other bacteria – but like almost all other life on Earth, including us — they require chemicals called cholesterol and other sterols in their membranes. Mycoplasmas also have a distinctive ability to stick to the exterior of their host cells, and they often have bizarre, thread-like attachment organs to make this happen. Some have evolved “gliding” systems for crawling around on your cells that are found no where else on Earth.

They look funny, too. Unlike “regular” bacteria that come packaged as neat little balls or rods, mycoplasmas come in many flavors. Although a typical size and shape for a Mycoplasma is a sphere 0.2-0.3 micrometers in diameter – a tenth as wide as a more usual-sized bacterium – they can also be larger and swollen, or branched or unbranched threads of many lengths that look more like the filaments of fungi than bacteria. This is where the name Mycoplasma (myko is the Greek root for fungi) came from.

Mycoplasmas are so small that in the early days of biology, they were mistaken for viruses. They fooled scientists, who weren’t even entirely sure what viruses were yet, by passing through excruciatingly small filters that stopped “ordinary bacteria”. When scientists at last realized what viruses were in the 1930s – tiny packets of RNA or DNA surrounded by proteins, and not cells at all – they realized Mycoplasmas were definitely not viruses. In reality, they were pint-sized bacteria.

But in other ways, these seemingly simple cells have evolved some incredibly complex machinery. They evolved unique gliding engines seemingly from scratch. Disease-causing Mycoplasma pneumoniae have evolved a “inchworm”-like system for inching around on your cells.

Mycoplama mobile, a parasite originally isolated from the gills of a fish called a tench, is a lightbulb-shaped bacterium that has a system of “legs” across the neck of the “bulb” that allow it to walk like a centipede on many, many tiny feet over the gills of their fish hosts. Scientists trying to figure out what molecule powers this system punched holes in its membranes, gutted it, and added a fuel called ATP only to create undead Mycoplasma zombies that were able to crawl around just as if they were alive (see Youtube video of undead Mycoplasma).

What might explain this apparent contradiction between simplicity and complexity? Mycoplasmas have a mutation rate 50% higher than that of the bacteria they evolved from, which may have allowed them to more quickly and easily shrink the size of their DNA at the same time they were able to experiment more easily with “rare evolutionary possibilities” – like, say, an entirely new cellular propulsion system.

And, most likely, right now many of these pip-squeak bacteria are making themselves at home in you. Most of them are minding their own business. They make a living on a tiny fraction of the byproducts in your respiratory and urogenital tracts, and they don’t cause trouble. These kinds of bacteria are called “commensals”, and many, if not most, mycoplasmas fall into this category. Mycoplasma orale and Mycoplasma salivarium, for instance, may be camped out on your tongue right now.

But there are also mycoplasmas who do not always mind their own business. These mycoplasmas, like M. pneumoniae and M. genitalium, can cause pneumonia, urinary tract infections, and pelvic inflammatory disease. Some mycoplasmas may even crawl out of the mucus membranes they normally live in and sneak into bone joints where they may cause arthritis, a painful stiffening older adults often experience.

16 species of Mycoplasma have been found in humans, but only about four or five cause us to get sick. Dogs and cats also host many MycoplasmasM. felis infects cats and M. cynos infects dogs, and there are many other commensal species living with them, too. And scores of other animals host mycoplasmas: cows, sheep, goats, horses, pigs, rats, mice poultry, seals, elephants, lions, pumas, voles, shrews, Chinese hamsters, Norwegian rats, and of course, the lowly tench. They seem to be everywhere we take the time to look.

How did mycoplasmas end up as tiny, shape-shifting hitchhikers inside tench, shrews, and you? Lots and lots of evolution. The lineage of wall-less bacteria that gave rise to mycoplasmas evolved some 600 million years ago from walled, free-living bacteria, just at the time the Cambrian Explosion – the sudden evolution of nearly all the major groups of marine animals – was beginning. The genus Mycoplasma itself evolved about 410 million years ago, about the same time animals crawled onto land and swapped fins for legs. About 190 million years ago, mycoplasmas started evolving several times faster than they had before around the same time that mammals evolved. As new species of mammals evolved, this may have provided more niches for new Mycoplasma species to evolve into, quickening their evolution.

Through all this close contact with their animal hosts over hundreds of millions of years, mycoplasmas shed many of the genes that truly free-living bacteria depend on as they learned they could find a steady supply of those products elsewhere. Living in a stable, safe aquatic environment (us) where they didn’t have to worry about exploding due to chemical changes in the fluid they lived in, they lost their cell walls. They made up for the loss by stealing rigid, planar molecules called cholesterols from our cell membranes, which helped strengthen and stabilize their cell membranes in the absence of a wall. No longer needing to synthesize many of their own basic foodstuffs because they could just take them from their hosts (that would be us again), they lost the genes for many of these too. Result: stripped-down, tiny, streamlined bacteria – the Mini-Coopers of the microbial world.


Brock biology of microorganisms (2009)
San Francisco, CA : Pearson/Benjamin Cummings, c2009. 12th ed.

Molecular biology and pathogenicity of mycoplasmas (2002)
New York : Kluwer Academic/Plenum Publishers, c2002.

Mycoplasmas : molecular biology and pathogenesis (1992)
Washington, D.C. : American Society for Microbiology, c1992.

About the Author

Jennifer Frazer is a freelance science writer fascinated by lifeforms without vertebrae. She blogs at The Artful Amoeba for Scientific American and has written for Scientific American online, Nature, Grist, High Country News, and the Wyoming Tribune-Eagle, where she worked as a health and environment reporter for three years, competed in the Chugwater Chili Cookoff, and wrote the stories on a mysterious elk die-off that earned her a 2007 AAAS Science Journalism award. You can find her on twitter @JenniferFrazer.