Sustaining symbiosis – new clues
The “kill all the bacteria” crowd are loath to admit it, but we rely on bacteria for survival. Deep in the human gut, trillions of symbiotic bacteria make vitamins, help digest food and fight disease.
Symbiosis is the classic “you scratch my back and I’ll scratch yours” relationship, and it’s everywhere in biology: Coral is a mutual-benefit society between photosynthetic algae, which provide food, and the coral animals which eat that food and build a “home” for the algae. Plants feed fungi growing on their roots, because those fungi extract nutrients from the soil.
But how does a host plant or animal make sure its pet microbes don’t run amok? And how does the microbe avoid attack by the host’s immune system?
Those are “burning questions” for the biologists of symbiosis, says Margaret McFall-Ngai, a professor of medical microbiology and immunology at the University of Wisconsin-Madison.
For about 20 years, McFall-Ngai has been studying the bobtail squid, a small, defenseless critter that lives in warm water in the Pacific. The bobtail has a problem, and it’s not people interested in squid sushi: When it hunts near the ocean surface, its shadow would make it an easy target for predators lurking below.
This so-called “flashlight squid” solves this problem with a symbiotic relationship with a luminescent bacterium called Vibrio fischeri. This bug, a relative of the one that causes cholera, glows inside the squid in return for food and shelter. But that shelter is not forever: the squid only needs light at night, when it’s active. During the day, when the squid burrows in the sand, the light is unnecessary.
Fifteen years ago, McFall-Ngai and coworkers discovered that the squid were ejecting about 90 percent of their bacterial cargo each morning, about the time they sink to the ocean floor for protection.
Is this what passes for gratitude in the dog-eat-dog world of biology?
Anyway, the remaining bacteria multiply during the day, so by nightfall, the squid contain enough bacteria to switch on that protective flashlight as they head upward to feed.
How does this happen?
In a new study, McFall-Ngai, Edward Ruby and colleagues studied the changing daily pattern of gene expression in the squid and the bacteria. The scientists took samples four times a day, including just before and after the squid “spat out” the bacteria, then put the samples on detectors capable of recognizing particular strands of RNA. Because RNA is patterned on DNA, that info told the researchers which genes were active at each sampling time.
“One fact that popped out right away, was that just before dawn, the vast majority of the genes associated with the squid’s cytoskeleton were activated,” says McFall-Ngai. The cytoskeleton is composed of microscopic strands that shape a cell, and also determine the location of its sub-structures, called organelles. “It looked as if the cells were preparing for something at 4 a.m., so we decided to look with a microscope at around that time, and we found that the squid tissue that normally houses the bacteria looked like dogmeat.”
More specifically, the tissue was missing tiny projections, called microvilli, that house bacteria and help them multiply. These structures, which resemble those found in the human intestines, “hug the bacterial symbionts,” McFall-Ngai says, “but after the squid expels the bacteria, the surface looks like it has been shaved; the microvilli are no longer present, and the surface of the cells is flat.”
No dumb bug…
Similarly, the bacteria had their own routine changes in genetic activity. As the squid sheds the microvilli, the un-evicted bacteria start making proteins that help them digest the microvilli, McFall-Ngai says. “The bacteria somehow sense that they are being presented with a huge pool of resource molecules in these animal membranes, and they turn on genes and pathways that let them digest those membranes.”
Later, after the membrane meal is masticated, the bacteria switch to a different set of enzymes that digest chitin, a structural molecule in the squid.
The symbiotic situation in the human gut is phenomenally more complicated, as we house hundreds of species of bacteria, rather than the loner living in the flashlight squid. But cycles of genetic activity have recently been recognized in mammalian intestines, McFall-Ngai says. “Biologists have shown a very significant 24-hour rhythm in the immune system of the gut, and also in the epithelial cells that line the gut, which have a close interaction with the countless gut microbes.”
Too close for comfort?
The supreme simplicity of the squid is its benefit, she adds. “We can ask questions with incredible precision; it’s just one host and one microbe, but we hope that what we find will be more widely applicable. To our knowledge, this is one of the first attempts to ask questions about symbiosis at the level of gene expression. We found that persistence of the symbiosis involves a daily fluctuation between what appears to be very healthy interaction and what looks like a disrupted, almost pathogenic, situation.”
Both partners in a symbiosis must “let their guard down,” but that, like every other aspect of the relationship, requires moderation, McFall-Ngai says. “Once you get the symbiosis started, you have to keep it going through the life of the host. How do you make sure the immune system does not get rid of the bacteria, or the bacteria do not overgrow the host? There has to be a balancing mechanism so it persists in a healthy condition. It may look like an uneasy alliance. To keep the symbiosis going, the squid has to do something drastic. But it works…”
– David Tenenbaum