Germs help each other fend off antibiotics

Drug-resistant infections are a big — and growing — problem. Most are caused by bacteria that have evolved genetic changes, called mutations, which make them immune to the cell-killing effects of antibiotics. A new study finds that these germs are more likely to survive antibiotics if the bacteria don’t have to face the cell killers alone. By working in groups, bacteria can share chemicals — making each germ better able to resist attacks by the medicines.

For their study, researchers at Vanderbilt University in Nashville, Tenn., worked with the bacterium Staphylococcus aureus. It’s known as staph, for short.

This germ causes a variety of infections. Many can be life threatening. Most staph infections occur during a hospital stay. These can affect blood, bone or other tissues. The germs also can lead to pneumonia. Outside hospitals, staph is more likely to cause skin infections. These infections often affect people who play contact sports.

Through mutations, staph — like many germs — can develop into new strains. While not a new species, a new strain will have new features. This happens because the mutation produces changes in the types or amounts of chemicals that an organism makes. And among some strains of staph germs, those new traits let the bacteria survive an assault by commonly used antibiotics.

These traits often evolve when the bacteria are exposed to the same types of antibiotics for decades. Along the way, some staph germs will develop DNA changes — those mutations — which protect them from the drugs. (The best known of these mutant germs is called MRSA, for methicillin-resistant Staphylococcus aureus. Methicillin is a widely used antibiotic.)

The new study looked at staph germs that could survive different types of drugs. All the bacteria were living together. And each shared some of the different drug-defense chemicals that it had made. This swapping now allowed the germs to fend off the effects of antibiotics. More of them became superbugs — germs that could laugh at multiple antibiotics — than if they had been fighting those drugs on their own.

Eric Skaar of Vanderbilt and his coworkers published their findings October 8 in Cell Host & Microbe.

Bad news: Neighbors helping neighbors

Some drug-resistant bacteria developed mutations that stop antibiotics from entering the cell, Skaar notes. But these mutations also stop cellular respiration. That’s the process by which the cells turn food into energy. If respiration shuts down, cells cannot grow well and multiply.

Without respiration, the germs don’t die. Instead, they turn on a process called fermentation. This process makes energy by breaking down sugars. But this process makes much less energy than respiration does, Skaar points out.

That should be good news for us. Bacteria that make less energy should be weak. These cells still might be resistant to antibiotics, but they would find it difficult to reproduce fast enough to overcome the body’s ability to kill them. Yet time and again, MRSA staph cells have proven themselves able to overcome this and cause serious disease. That made Skaar’s team wonder if those different staph strains might be helping each other to overcome their weaknesses.

To find out, the researchers used two strains of staph. One had a mutation that kept the germs from making an enzyme that produces heme. Heme is an iron-based compound also found in red blood cells. The other mutant staph strain lacked the enzyme to make vitamin K. (Bacteria in our gut make this vitamin, which helps us by allowing blood to clot.)

When working properly, both enzymes move antibiotics into the germ. So staph strains unable to make either enzyme are protected against killer antibiotics. They don’t die. But since the germ cells need both heme and vitamin K for respiration, the affected cells could make only tiny colonies. 

That changed when the researchers mixed the two strains of staph. Suddenly, the bacteria began thriving again. And the bad news: They still fended off the antibiotics.

The strains that could not make heme still made vitamin K, Skaar’s team showed. And the strains not able to make vitamin K still produced heme. But when they lived together, the two mutant strains shared. They somehow offered their neighbor the important chemical they needed but couldn’t make themselves. This allowed both strains to become a much bigger threat. They grew well and were immune to the effects of the drugs meant to kill them.

The mutant staph strains could even borrow the missing compounds that it needed from other species of bacteria, the researchers showed. That means drug-resistant staph can pick up those essential compounds from the “good” bacteria already in our bodies.

The study suggests how superbugs can stay virulent even when part of their survival machinery is crippled, says Robert Daum. (Virulence refers to the ability of a germ to cause disease.) A microbiologist at the University of Chicago in Illinois, Daum was not involved with the study.

The findings may point to where new efforts to fight staph infections should focus, says Skaar. He envisions a “sponge” of sorts that might soak up those essential compounds before they might be shared. If such a strategy worked, it might turn some superbugs into wimps.

Power Words

antibiotic  A germ-killing substance prescribed as a medicine (or sometimes as a feed additive to promote the growth of livestock). It does not work against viruses.

bacterium (plural bacteria)  A single-celled organism. These dwell nearly everywhere on Earth, from the bottom of the sea to inside animals.

cell   The smallest structural and functional unit of an organism. Typically too small to see with the naked eye,it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size.

chemical      A substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H₂O.

clot    (in medicine) A collection of blood cells (platelets) and chemicals that collect in a small region, stopping the flow of blood.

compound    (often used as a synonym for chemical) A compound is a substance formed from two or more chemical elements united in fixed proportions. For example, water is a compound made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H₂O.

DNA  (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

enzymes   Molecules made by living things to speed up chemical reactions.

fermentation  The metabolic process of converting carbohydrates (sugars and starches) into short-chain fatty acids, gases or alcohol. Yeast and bacteria are central to the process of fermentation. Fermentation is a process used to liberate nutrients from food in the human gut. It also is an underlying process used to make alcoholic beverages, from wine and beer to stronger spirits.

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.

heme     A deep red iron-containing pigment in blood and responsible for its red color. Heme is part of hemoglobin, the oxygen-carrying molecule in red blood cells.

infection    A disease that can spread from one organism to another.

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.

microbe  (short for microorganism )   A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.

MRSA   An abbreviation for methicillin-resistant Staphylococcus aureus. Methicillin is a widely used antibiotic. And Staph aureus is a bacterium that can cause boils, food poisoning, toxic-shock syndrome and more. These bacteria sicken (and sometimes kill) by releasing into the body potent natural poisons, called toxins.

mutation  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.

pneumonia  A lung disease in which infection by a virus or bacterium causes inflammation and tissue damage. Sometimes the lungs fill with fluid or mucus. Symptoms include fever, chills, cough and trouble breathing.

red blood cells  Colored red by hemoglobin, these cells move oxygen from the lungs to all tissues of the body.

resistance    (as in drug resistance) The reduction in the effectiveness of a drug to cure a disease, usually a microbial infection.

respiration   The process by which organisms produce energy from sugars, usually by taking in oxygen and releasing carbon dioxide.

species  A group of similar organisms capable of producing offspring that can survive and reproduce.

Staphylococcus aureus    (also known as staph) A species of bacteria that is responsible for a number of serious human infections. It can cause surface abscesses, or boils. If it gets into the bloodstream, where it can be carried throughout the body, it may also cause pneumonia and infections of the joints or bones.

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 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.

virulence  (in medicine) The potency of a virus, bacterium or other agent in causing infectious disease. Among a given species, some strains may cause disease with very little exposure (such as infection with a few cells). Less virulent strains may take massive exposures to create disease.

vitamin  Any of a group of chemicals that are essential for normal growth and nutrition and are required in small quantities in the diet because they cannot be made by the body.