Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (3 page)

Without microbes, we could not eat or breathe. Without us, nearly all microbes would do just fine.

The term
microbe
refers to several types of organisms. In this book, I will be talking mostly about the domain of bacteria, also called
prokaryotes
, single-cell organisms that lack a nucleus. But that doesn’t mean they are primitive. Bacterial cells are complete, self-contained beings: they can breathe, move, eat, eliminate wastes, defend against enemies, and, most important, reproduce. They come in all shapes and sizes. Some look like balls, carrots, boomerangs, commas, snakes, bricks, even tripods. All are exquisitely adapted for how they make a living in this world, including those, as I’ll elaborate in the next chapter, that thrive on and within our bodies. When they go AWOL, we are in trouble.

Another microbial domain, called
archaea
, superficially resemble bacteria but, as their name suggests, they are a very old, very deep branch of the tree of life with different genetics and biochemistry and an independent evolutionary history. Originally found in extreme environments, such as hot springs and salt lakes, archaea actually may be found in many niches, including the human gut and belly button.

The third branch of microbial life is composed of
eukaryotes
, single cells with a nucleus and other organelles that provide the building blocks for more complex, multicellular forms of life. Over the last 600 million years, eukaryotes have given rise to insects, fish, plants, amphibians, reptiles, birds, mammals—all the “big” life from ants to redwoods that you can see around you. However, some primitive eukaryotes are lumped in with microbes, including fungi, primitive algae, some amoebae, and slime molds.

Here is another kind of scale. Everyone is familiar with a family tree. Your ancestors are lined up by generation with the oldest great-grandparent first, followed by your grandparents, and so forth, expanding the numbers with each generation. Now imagine a family tree of all life on Earth. There are so many forms of life that rather than a tree, it looks more like a bush, with branches extending in all directions. Imagine for the moment that it is a round bush, with the first generation, the origin, near the center and the branches extending outward. Next, let’s place us humans on the bush, somewhere around eight o’clock on a watch dial.

Now for the quiz. Where is the life-form on farms that we call corn on that bush? All things equal, we don’t think that we are so close to corn, which, after all, is a green plant; maybe it is halfway around the bush? Wrong, it is at about 8:01. If humans and corn are so close, who is taking up the rest of the bush of life and its branches? The answer: It is mostly bacteria. For example, the distance between
E. coli
and
Clostridium
—two common bacteria—is much greater than the distance between corn and us. Humanity is just a speck in the massively bacterial world. We need to get used to that idea.

And then there are viruses, which are, strictly speaking, not alive; they propagate by invading and co-opting living cells. We think about viruses like the flu, the common cold, herpes, and HIV as problems of humans. But most of the viruses in the world are completely irrelevant to us; their targets are bacterial cells, not animal cells like ours. In the oceans, the number of virus particles is unfathomable, more than all the stars in the universe, living off the myriad bacteria in the waters. Over the billions of years that viruses and microbes have been duking it out, each has evolved weaponry to defeat the other. It reminds me of the classic
Spy vs. Spy
comic strip in
Mad
magazine. In fact, one possible treatment for bacterial diseases in humans involves harnessing
phages
—viruses that kill bacteria—an idea I discuss near the end of the book.

While many types of microbes inhabit and shape our world, my main focus here is on bacteria and what happens when we kill them indiscriminately with potent drugs. Although there are plenty of eukaryotes (such as
Plasmodium falciparum
, one of the major causes of malaria) that lead to great misery, the problems they pose are of a different nature. And there are viruses that cause much harm—think about HIV—but they do not respond to antibiotics and are a topic for a different day.

*   *   *

Microbes make their homes everywhere we look. The ocean is home to unimaginable numbers of them, though some estimates give a flavor to their ubiquity. At least 20 million types of marine microbes (possibly a billion) make up 50–90 percent of the ocean’s biomass. The number of microbial cells in the water column, meaning sea surface to sea floor, is more than 10 to the 30th, a nonillion, or 1,000
×
1 billion
×
1 billion
×
1 billion. This is equal to the weight of 240 billion African elephants.

The International Census of Marine Microbes, a decade-long project that has been sampling marine microbes from more than twelve hundred sites around the world, estimates there may be one hundred times as many microbial families (genera) as previously thought. Everywhere scientists have looked, some species dominate in terms of numbers and activity. But in what came as a surprise, they also found many species represented by fewer than ten thousand individuals (a puny number for bacteria), including one-off singletons. They concluded that many rare bacteria in the oceans are lying in wait, ready to bloom and become dominant if environmental changes favor them. The same concept holds true for the microbes that inhabit our bodies. The ability to “lurk” for long periods of time in small numbers and then spontaneously “bloom” is an important feature of microbial life.

Many marine microbes are so-called extremophiles. They live in hydrothermal vents where boiling water rich in sulfur, methane, and hydrogen rises from the mantle to meet frigid water, forming conelike chimneys. It is a hellish mixture of acids and heavy chemicals, but it is one in which rich communities of bacteria thrive in the absence of oxygen and sunlight. We see the same thing in the superhot pools and geysers at Yellowstone National Park in Wyoming and in the bubbling tar lake found on the Caribbean island of Trinidad. Bacteria also live in the massive glaciers of Antarctica and under the frozen depths of the Arctic Ocean.

Oceanic crust composed of dark, volcanic rock at the bottom of the sea, encompassing 60 percent of Earth’s surface, is home to perhaps the largest populations of microbes on the planet. Its resident microbes live off energy obtained from chemical reactions between water and rock.

Recently, bacteria have been found munching on plastic particles floating in the open oceans. Although a slow process, at least one thousand different species are involved in converting this “plastisphere” to a healthier biosphere. Other than dump plastic in the ocean, we didn’t do anything to stimulate these bacteria. From among the countless varieties floating about, some found their way to the plastic, and those that found it a favorable food source grew in numbers—natural (plastic) selection in action.

The deepest place on Earth, the Marianas Trench, was recently found to support an active microbial community with ten times more bacteria than those in the sediments of the surrounding abyssal plain. And gigantic mats of microbes—the size of Greece—live on the seafloor off the west coast of South America by consuming hydrogen sulfide.

Abundant microbes are lofted by winds, including hurricanes, where they persist and may even make their living high in the skies. They help form cirrus clouds and nucleate ice particles to make it snow. They influence both weather and climate as well as recycle nutrients and decompose pollutants.

Down on the ground, microbes are in charge of soil, one of our most precious resources. Projects to sample soil bacteria worldwide are just getting under way in what some experts call the search for Earth’s dark matter, an undertaking akin to figuring out the nature of unknown realms of the cosmos.

We know that microbes make the planet habitable. They decompose the dead, which is a very useful service. And they convert or “fix” inert nitrogen in the atmosphere into a form of free nitrogen that can be used by living cells, benefiting all plants and animals. After the Deep Water Horizon oil spill in the Gulf of Mexico, bacteria ate up much of the contamination because they were able to supplement the nutrients in the oil with nitrogen that they could remove from the air to form a complete meal for themselves.

Microbes live in rocks. For example, in South Africa’s Mponeng gold mine, bacteria survive with the help of radioactive decay as uranium splits water molecules, releasing free hydrogen, which the bacteria combine with sulfate ions to make dinner. They even mine the gold.
Delftia acidovorans
uses a special protein to convert floating ions of gold, which are toxic to it, into an inert form of the metal that precipitates from the surrounding water and accumulates in mineral gold deposits. Meanwhile, perhaps the world’s toughest bacterium,
Deinococcus radiodurans
, lives on radioactive waste.

But my favorite was described several years ago. Geologists were drilling an exploratory well and studying the cores that came up. From one core taken a mile down, they found only three constituents: basalt (a form of bedrock), water, and bacteria—loads of them. These bacteria made their living and reproduced on just rock and water.

Finally, whole industries are based on harnessing microbes to do our bidding, from making the bread that nourishes us, the alcohol we drink, to the modern drugs engineered by the biotech field. It is fair to assume that bacteria can do just about any chemical process that we might assign to them. In their endless variety are found untold capabilities. We just have to define the problem and go after the right microbes to solve it or we will need to reengineer them. But those exciting possibilities are subjects for another time.

*   *   *

The story of microbes is a saga of limitless warfare and also endless cooperation. Since most people are familiar with Darwinian competition and survival of the fittest, I’ll start there.

Darwin’s careful observations showed that there always was variation among individuals of any species, from birds to humans. He developed his theory of evolution by positing that when variants exist, nature will “select” the one(s) that are best adapted (“the fittest”); these are the ones that best complete their life cycle and have descendants. They outcompete the other variants. Over the course of time, they will crowd out their competitors, even to the point of extinction. It is this natural selection that leads to the commonly stated “survival of the fittest.” But Darwin did not know it also pertained to microbes. Like us, he was focused on things he could see—plants and animals—but the fact is that some of the best evidence for natural selection comes from observations and experiments involving microbes.

For example, I can grow a culture of the common intestinal bacterium
E. coli
by placing a tiny dot of existing cells on a plate that nourishes their growth. After an overnight in a warm incubator, the fast-growing
E. coli
might expand to 10 billion cells. The entire plate is covered with a lawn of
E. coli
cells, the growth so dense that individual colonies cannot be seen. Now let’s say that I do the same inoculation to another plate, but I add streptomycin, an antibiotic that kills most
E. coli
strains. The next morning when I look at that plate, I only see 10 isolated colonies instead of the lawn of 10 billion cells. Each little colony, the size of a smallish pimple, might have a million
E. coli
cells. Each colony was derived from a single cell that survived the antibiotic and then multiplied on the plate. How do we explain the difference in outcome when we inoculate bacteria onto plates with and without the streptomycin?

First, we can see that the antibiotic worked. Instead of 10 billion cells on the plate, there only are 10 million, a thousandfold reduction. One way to look at it is that the antibiotic killed 99.9 percent of the cells, allowing only a small number to survive. We also can see that the antibiotic failed to some degree. Some cells survived its actions. Why did these cells survive whereas the others did not? Dumb luck? The answer is both yes and no.

The lucky part is that cells resistant to streptomycin possess a variant of a gene that all
E. coli
need to make proteins essential for their survival. The variant gene is not particularly efficient, but it’s good enough to help the resistant strains survive and keep making descendants. The susceptible cells die because the antibiotic interferes with the usual version of the same protein, which is essential for cell growth.

These genetic variants that confer resistance arise in an interesting way. It’s possible that a few of the cells (ten to be exact in this illustration) in the original culture of a billion cells had the variant gene. They were preexisting. To put these experiments into Darwinian terms, the presence of streptomycin “selects” for the variants in the population that have a resistant form of the gene, whereas the absence of streptomycin in the environment “selects” for the usually more efficient streptomycin-susceptible form. The frequency of the
E. coli
cells with streptomycin resistance would depend on how often streptomycin was around and also how recently. This is a simple example of natural selection, but competition is eternal. May the best microbe win.

While bacteria compete with, prey on, or exploit others, we also see countless instances of cooperation and synergy. For example, if a
Bacteroides
bacterium in the gut can detoxify a chemical in the environment that inhibits
E. coli,
then
E. coli
benefits. A one-way helpful relationship like this is called
commensal
.

Interactions are even more powerful when the benefits are mutual. Imagine that
E. coli
’s main waste product turns out to be a good food source for
Bacteroides
. In this case, the two species will tend to congregate in the same environments. Each is doing nothing more than following its own program, but ultimately they help each other; this is
symbiosis
.