Harvard Medical School
Germs are everywhere. Fortunately, most pose no risks to people. And those that do cause disease usually can be killed with antibiotic drugs. Sometimes, however, harmful bacteria evolve ways to “laugh at” antibiotics — survive as if the poisons were not even there. This so-called drug resistance make infections hard, if not impossible, to treat. How bacteria learn to resist killer drugs normally is invisible. But scientists have just unveiled a new tool that lets them watch it happen, right before their eyes.
“As someone who’s studied evolutionary biology for a long time, I think it has a real wow factor,” says Sam Brown. He is a microbiologist at the Georgia Institute of Technology in Atlanta. Brown applauds those who developed this new tool. Looking at it, he says, is like watching bacteria “climbing this impossible mountain of antibiotics.”
Antibiotic-resistant germs don’t look any different than ordinary ones. To identify them, scientists must spy on how they grow, looking for ones that still spread even when an antibiotic drug is around.
For this type of study, scientists usually place bacteria in a liquid growth medium — food, essentially — within a bottle-like flask. Then they jiggle the flask. This makes the bacteria slosh around. Over time, they run into everything in the liquid. Those that adapt to any drugs will eventually grow more quickly, and eventually outnumber all other germs in the flask.
But that flask isn’t much like nature, notes Michael Baym. He is a microbiologist at Harvard Medical School in Boston, Mass. He and his team decided to instead spy on bacteria living on a flat surface. This, after all, would better resemble the sites where bacteria might encounter drugs, such as on hospital counters, door knobs and medical equipment.
On a flat surface, germs ‘see’ only whatever is right next to them, Baym explains. To adapt there, they don’t have to be the best in the whole community. They just have to be survive on whatever real estate is next door.
Microbiologists tend to grow germs in a Petri dish. This is circular, low-walled dish that has a goo rich in nutrients — agar — spread across its bottom. A standard Petri dish is about the size of a human palm. Baym’s team instead created a much larger flat plate. Theirs was a whopping 60 by 120 centimeters (2 by 4 feet) in size. That makes it nearly as large as a foosball table! They called it this plate MEGA, which stands for Microbial Evolution and Growth Arena.
The scientists added one of two common antibiotic drugs to the growth medium spread across the plate: either trimethoprim or ciprofloxacin. But they didn’t add the same amount everywhere. They put small amounts of a drug in the agar that had been spread along the sides of the plates. Then, in bands of agar, they increased the dose of a drug as its distance from the edges increased. They put the highest dose of drug in a band running through the middle. Next, the researchers placed bacteria along the low-dose sides of the plate. These germs were a common version — or strain — of Escherichia coli (Esh-ur-EESH-ee-uh KOH-lye). This germ is best known simply as E. coli.
With the system all set up, the scientists sat back and watched the bacteria grow. The bacteria quickly spred across the bands of agar containing a very low level of a drug. When they reached the edge of the band where the next higher level of poison was located, the cells abruptly stopped spreading. Those that couldn’t live on the higher level of poison either died off or just stopped.
But in a short while, some of the E. coli mutated. That means their genes changed — evolved — in ways that helped them adapt. This let them survive the poison. These strains of the germ now spread into the next band of agar. When they again met a much higher dose of the drug they again stopped. But that didn’t last forever. Before long, some of the bacteria evolved, broke through and began migrating into the next band of agar.
This pattern continued over and over. During some 10 to 12 days, the bacterial colonies spread onward toward the center of the plate. Eventually some arrived at — and colonized — the middle. The drug level there was 1,000 times as high as had been needed to kill some of the initial bacterial pioneers. But eventually, some settlers developed mutations that allowed them to grow even on these strongest dose of poison. Doctors refer to such highly-resistant germs as “superbugs.”
Interestingly, the bacteria that advanced the fastest into the high-drug bands were not always the most super of the superbugs. For some germs, adapting to life with the drugs slowed their growth. This might trap them behind the faster advancing but not as drug-resistant pioneers.
The new findings are important because they can help scientists learn how antibiotic resistance evolves.
Baym and his colleagues think their MEGA-plate could be used to study how bacteria respond to other types of environments also. For example, bacteria may evolve differently when there is not much food available.
His team described its findings in the September 9 issue of Science.
(for more about Power Words, click here)
agar A gelatinous material made from certain marine algae used as a material (and food source) in which to grow bacteria.
antibiotic A germ-killing substance, usually prescribed as a medicine (or sometimes as a feed additive to promote the growth of livestock). It does not work against viruses.
bacterial Having to do with bacteria, single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside animals.
biology The study of living things. The scientists who study them are known as biologists.
colleague Someone who works with another; a co-worker or team member.
E. coli (short for Escherichia coli ) A bacterium that researchers often use to study genetics. Some types of this microbe cause disease, but many other forms of it do not.
environment The sum of all of the things that exist around some organism or the process and the condition those things create for that organism or process. Environment may refer to the weather and ecosystem in which some animal lives, or, perhaps, the temperature, humidity and placement of components in some electronics system or product.
evolution (v. to evolve) A process by which species undergo changes over time, usually through genetic variation and natural selection. These changes usually result in a new type of organism better suited for its environment than the earlier type. The newer type is not necessarily more “advanced,” just better adapted to the conditions in which it developed.
evolutionary biologist Someone who studies the adaptive processes that have led to the diversity of life on Earth. These scientists can study many different subjects, including the microbiology and genetics of living organisms, how species change to adapt, and the fossil record (to assess how various ancient species are related to each other and to modern-day relatives).
evolve (adj. evolving) To change gradually over generations, or a long period of time. In living organisms, the evolution usually involves random changes to genes that will then be passed along to an individual’s offspring. These can lead to new traits, such as altered coloration, new susceptibility to disease or protection from it, or different shaped features (such as legs, antennae, toes or internal organs). Nonliving things may also be described as evolving if they change over time. For instance, the miniaturization of computers is sometimes described as these devices evolving to smaller, more complex devices.
flask A type of container with a narrow neck. In the laboratory, sterile flasks made from glass are used for conducting chemical and biological experiments.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
germ Any one-celled microorganism, such as a bacterium, fungal species or virus particle. Some germs cause disease. Others can promote the health of higher-order organisms, including birds and mammals. The health effects of most germs, however, remain unknown.
infection A disease that can spread from one organism to another. It’s usually caused by some sort of germ.
mass A number that shows how much an object resists speeding up and slowing down — basically a measure of how much matter that object is made from.
mega A prefix for units of measurement meaning million in the international metric system.
microbiology The study of microorganisms, principally bacteria, fungi and viruses. Scientists who study microbes and the infections they can cause or ways that they can interact with their environment are known as microbiologists .
mutation (v. mutate) Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.
nutrient A vitamin, mineral, fat, carbohydrate or protein that a plant, animal or other organism requires as part of its food in order to survive.
Petri dish A shallow, circular dish used to grow bacteria or other microorganisms.
resistance (as in drug resistance) The reduction in the effectiveness of a drug to cure a disease, usually a microbial infection, by knocking out a germ.
risk The chance or mathematical likelihood that some bad thing might happen. For instance, exposure to radiation poses a risk of cancer. Or the hazard — or peril — itself. Among cancer risks that the people faced were radiation and drinking water tainted with arsenic.
strain (in biology) Organisms that belong to the same species that share some small but definable characteristics. For example, biologists breed certain strains of mice that may have a particular susceptibility to disease. Certain bacteria or viruses may develop one or more mutations that turn them into a strain that is immune to the ordinarily lethal effect of one or more drugs.
superbug A popular term for a disease-causing germ that can withstand medicines.
technology The application of scientific knowledge for practical purposes, especially in industry — or the devices, processes and systems that result from those efforts.